Projects Supported by the netCAD Blood4Research Program

Project ID: 2018.018b4r

Title: Investigating human immune tolerance in humanized mouse model 

Project Approval Date: 2018-05-17

City: Toronto

Type of Organization: Academic  

Use of Animals: Yes

Canadian Blood Services Mandate: Transplantation medicine

Summary: For the patients who need the organ or therapeutic cell transplantation, immune rejection following the transplantations means the host immune system recognize the transplant as non- self and start to attack the transplant. Immune rejection threatens patients life and in clinics, immunosuppressive drugs can help inhibit the immune system and increase the transplant survival rate. However, there are many long term side effects such as toxicity of immunosuppressive drugs, higher infection risk and graft versus host disease (GVHD). We aim to explore how to induce the local immune tolerance and recipient in order to protect donors organ/tissues/cells After organ transplantation for better survival and life quality without immune suppressive drugs. Considering the ability of human pluripotent stem cells (hPSCs) to differentiate into different mature lineages, such as retinal pigment epitheliums (RPE). our approach is to genetically modify human pluripotent stem cells and screen the candidate immunomodulatory genes that have potential functionalities to regulate the immune rejection to non-self organs/tissues/cells.

Project ID: 2019.001b4r

Title: Studying anti-inflammatory and anti-cancer agents using primary peripheral blood mononuclear cells 

Project Approval Date: 2019-03-26 

City: Sudbury

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: This study is able to investigate the toxicity of small molecules and their ability to act as anti-inflammatories on primary immune cells. These cells we reextracted from the buffy coats of healthy, anonymous donors, which has been performed repeatedly for these studies. Once the primary peripheral mononuclear cells(PBMCs)have been extracted standard molecular biology techniques are then applied to study these cells under various treatment conditions. We have collected cells from four healthy donors (viaCBS) which has been sufficient for experiments to date. We have successfully investigated different agents using PBMCs and our results demonstrate that these small molecules are non-toxic when used at doses that are able to induce both anti-cancer and anti-inflammatory effects. We are continuing with our preclinical investigations of these agents in various inflammatory conditions that represent either infection or autoimmune conditions to try and flush out the mechanisms of action to better understand these agents. The potential impact of the study it its continued development of new therapies for cancer, arthritis and potentially other inflammatory conditions.

Project ID: 2019.023b4r

Title: Immunocompetent Organ Models 

Project Approval Date: 2019-07-26  

City: Vancouver

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: Over the past 10 years, human-based skin models as alternatives to animal models emerged. Although  these  models  are  valuable  in  various  regards,  there  application  in  basic  and preclinical research is hampered by the lack of immune cells (1). Immune cells play a central role in skin homeostasis and the pathophysiology of skin diseases and are therefore a crucial element in skin models. In order to establish immunocompetent skin models, the isolation of PBMCs  and  immune  cells  from  buffy  coat  will  be  done  which  is  a  standard  procedure  (2). Various protocols are online available; specific isolation kits can be purchased commercially (3, 4). The same holds true for the subsequent generation of monocyte-derived immune cells from PBMCs (5).Hence, the overall aim of this project is the development of immunocompetent skin models for basic  and  preclinical  research.  These  models  are  alternatives  to  the  widely  used  animal models,  which  however,  differ  greatly  with  respect  to  skin  homeostasis  from  human  skin. Hence, secondary objectives of this proposal are: Generation/isolation of macrophages and T cells which will then be incorporated into organ (disease) models aiming for the establishment of  immunocompetent  human-based  organ  models  to  study (1)(patho)physiology  and/or (2)novel therapeutic approaches/drugs in vitro.We  usually  order  buffy  coats,  from  which  we  isolate  PBMCs  and/or  T  cells.  We  have successfully run first studies with T cell competent human-based organ models and first results indicate their suitability for the development of new anti-inflammatory drugs for the treatment of atopic diseases. We also have successfully implemented them in microfluidic organ-on-chip culture. The main challenge so far is to keep the immune cells alive for up to 7 days in a co-culture of 2 organ models. However, we are confident that we can solve this problem. Once we have established a stable co-culture for up to 7 days, we aremuch closer to developing a human-based model for atopic diseases which would be a significant advancement over the current state-of-the art. 

Project ID: 2019.028b4r

Title: Non-invasive tumour mutation profiling using circulating tumour DNA from blood 

Project Approval Date: 2019-10-22 

City: Vancouver

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transfusion medicine

Summary: Each year, >190,000 Canadians are diagnosed with cancer, and ~77,000 die from the disease. Genetic testing of archival tissue or freshly biopsied tumor tissue is required for most types of cancer to aid in diagnosis and treatment. While genetic testing is currently performed in tumor tissue, rapidly evolving technology will allow the majority of assays to be performed on circulating tumor DNA found in the blood. The advantages of a blood test (aka. Liquid biopsy) include reduced cost, reduced invasiveness and the ability to repeatedly test tumors as they evolve throughout the course of therapy. This project will develop a liquid biopsy assay to look for cancer mutations in the blood, as a diagnostic assay as well as a means to monitor patient response to treatment or cancer reoccurrence. We expect the assay will serve several provinces and research groups through our clinical testing laboratory, and help improve the management of cancer patients, and potentially reduce blood utilization.

Project ID: 2019.029b4r

Title: Red blood cell donor and storage study 

Project Approval Date: 2019-12-11 

City: Vancouver

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transfusion medicine

Summary: Red blood cells circulate in the bloodstream for approximately 120 days, delivering oxygen to all tissues in the body. A key property of red blood cells is their ability to squeeze into capillary blood vessels that are many times smaller than their own diameter. Donated red blood cells, collected by the Canadian Blood Service for use in blood transfusions, can be stored for up to 42 days. During this time, the deformability of these cellsis degraded, impairing their ability to circulate in capillary blood vessels. As a result, the viability of these cells in transfusion recipients is reduced from 120 days to, in some cases, hours or minutes. Currently, there are no simple methods to measure the quality of donated blood units, as defined by how long they will circulate in transfusion recipients. Additionally, there appears to be significant differences between donors, where some donors could provide blood that circulate longer in recipientsthan other donors.Our research team have developed a method to analyze red blood cell deformability by sorting these cells based on their deformability in order to determine if the more deformable red blood cells circulate for longer in recipients than less deformable cells. Using an accelerated aging model of RBCs stored in plastic tubes, we found that donor RBCs had degradation profiles that were highly variable between donors, but consistent for each donor. Importantly, some donors showed significant loss of RBC deformability during storage, while other donors showed little or no storage induced loss of RBC deformability. We show that, in most cases, blood bags preserved RBC deformability during the 42-day storage window, while the degradation of RBC deformability in the subsequent 14 days were highly variable. This trend was mirrored in blood unit segments (attached to the same blood bag unit) with a strong correlation to the blood bag data. Strong correlations were also observed between blood bag and segment for MCV, MCHC and MCH, but not for hemolysis. Our results confirm that RBC deformability provides a potentially useful approach for donor-level screening to identify donors for whom the storage expiration window could potentially be lengthened. 

Project ID: 2019.030b4r

Title: Characterizing the interactions between primary human macrophages and engineered biomaterials 

Project Approval Date: 2019-10-09 

City: Toronto

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transplantation medicine

Summary: Macrophages and T cells are immune cells whose behavior can be altered by a wide range of biochemical cues presented by tissues and other cells. Both the presence and treatment of disease, in addition to transplantation procedures can alter macrophage and T cell behavior to worsen or improve patient recovery and prognosis. Traditionally, biomaterials including water-swollen hydrogels composed of natural sugars and proteins have been used as implants and vehicles for drug delivery. More recently, biomaterials themselves have been shown to have effects on immune cell recruitment and macrophage phenotype, raising the question of what is the ideal material to study these cells. Primary human macrophage and Tcell behaviour is not previously been studied in materials that represent the diseased extracellular matrix, which could reveal relevant behaviour that could support treatment of disease. We have developed a material called a cryogel, which is a hydrogel that is formed using a freezing technique to introduce pores. This new material is made from gelatin and hyaluronan, two components that are upregulated in a variety of disease microenvironments. The pore size and stiffness of the material can be modulated using chemistry that is used to covalently bind the components together. We used buffy coats from CBS donors to isolate monocytes which we then differentiate to macrophages and seed on our cryo gels. We showed that the cryogel properties can influence cell migration, and we also show that the mechanism of migration through our gels is the same as that through in vivo tumour environments. We show that treatment with different proteins affects the migration capacity, which shows that we can use our cryogel to study relevant biological phenomenon. The first phase of this project has been published in Advanced Functional Materials. Our next stage of the project to be completed within one year will be co-culture with macrophages/T cells and diseased cells, to see the effects of cell-cell interactions on macrophage and T cell behaviour. This information could reveal drug targets, help us develop better disease models, and even discover insights to immune cell behaviour that could provide insights for transplantation research.

Project ID: 2020.003

Title: High circulating LDL causes inflammation contributing to heart disease 

Project Approval Date: 2020-03-20 

City: Ottawa

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: In heart disease, LDL accumulate in the arteries, where they become modified, aggregated and retained. Such deposits of aggregated LDL (agLDL) can be recognized by macrophages, which initiate the inflammation in the arteries. This will lead to recruitment of blood cells, create lesions in the arteries, which eventually blocks blood flow. We propose to research and understand the process, thereby exploring the options to prevent inflammation in the arteries to decrease heart diseases. This study is entirely in vitro. We are using mouse macrophages to provide novel information on how atherosclerosis is initiated. There is no patient involvement. To study this project, we need to use LDL to make agLDL. LDL is isolated from human plasma, which we obtain from Canada Blood Service. The results will provide new insight for the development of plaque in the arteries, which leads to heart attaches. By understanding the process, medical interventions could be developed to lessen the effect of agLDL. 

Project ID: 2020.005

Title: Donor characteristics and the quality of red cell concentrates 

Project Approval Date: 2020-02-26 

City: Edmonton

Type of Organization: Canadian Blood Services 

Use of Animals: No

Canadian Blood Services Mandate: Transfusion medicine

Summary: Red cell concentrates (RCCs) contain subpopulations of red blood cells (RBCs) at each stage of their 120-day lifespan. The age distribution of these cells is influenced by donor characteristics; a better understanding of donor effects on RBC subpopulations can help improve the quality of stored red blood cell products. As RBCs age, they become denser from cell membrane loss and dehydration. Differences in RBC subpopulation age/density allows cells to be separated into young (less dense) and old (more dense) using density gradient separation methods.This study will select donors based on age (< 30 years or > 60 years) and sex (male or female). The pre-donation hemoglobin levels (low or high) and donation frequency (> 3 or 1) of the donors will also be collected for further characterization of the samples. Cells will be separated using density gradient separation (Percoll) for quality analysis. It is suspected that young, female donors who donate more frequently and have lower hemoglobin levels will have a larger subpopulation of young, less dense RBCs. Results of this study will improve our understanding of the effect of donor characteristics on blood product quality and may result in changes to how blood components are produced and transfused. 

Project ID: 2020.010

Title: Understanding the invasion of red blood cells by malaria parasites 

Project Approval Date: 2020-02-20 

City: Quebec

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transfusion medicine

Summary: Malaria is one of the world’s most common infectious diseases, with approximately 274 million cases each year and 470000 deaths, and thus represents one of the most devastating global public health problems. The lack of an effective vaccine, resistance to all commercial antimalarial drugs, combined with the small number of suitable new drugs against the malaria parasite demonstrate the urgent need for the development and implementation of novel intervention strategies in the form of drugs, vector control measures and an effective vaccine. Indeed, it is expected that if the trend in malaria prevalence stays on its current upwards course, the death rate could double in the next twenty years. Invasion of a red blood cell by Plasmodium falciparumparasites is anessential step in the malaria lifecycle and host response to parasite antigens are an important component of human malarial immunity. Consequently, the molecular players involved in erythrocyte invasion are key targets for both therapeutic and vaccine-based strategies to block parasite development. Several of these invasion proteins are stored in the apical complex of the parasite, a structure containing secretory organelles called dense granules, micronemes and rhoptries, and are released at different times during invasion. Because of its essential role, interfering with the generation of the apical complex represents a very attractive target for the design of a new kind of antimalarial. Our studies will focus on trying to understand how the parasite directs proteins to the different structures of the apical complex. Understanding this complex process will likely provide a wealth of new targets for the development of strategies to block apical complex generation and preventing malaria pathogenesis. This could also lead to the development of antibody-based rapid diagnostic tests for the detection of malaria.

Project ID: 2020.018

Title: Modeling HIV spread between blood cells 

Project Approval Date: 2020-06-22 

City: Manitoba

Type of Organization: Academic 

Use of Animals: Yes

Canadian Blood Services Mandate: Transplantation medicine

Summary: The objective of this research project is to generate a “humanized” mouse model to study the early phases of HIV infection. Specifically, we will determine whether the biology of human white blood cells (e.g. T cells, B cells and monocytes) can be studied within a more physiological environment using a mouse model. The rationale is that the experimental conditions by which we study human white blood cells have an impact on their biology. Therefore, it is important to develop an animal model to study their behaviors within complex biological systems that closely recapitulates their natural setting. The goal is to understand how HIV infection alters the behavior and numbers of human white blood cells in blood, and to uncover new mechanisms that can be therapeutically targeted to suppress HIV replication. Our studies also have implications on understanding how HIV can impact transplantation of mice with human blood cells. To accomplish this, we will transplant 50 million human white cells from healthy blood donors (from buffy coats) and monitor their numbers in mice (e.g. blood, lymphoid organs). We will phenotypically characterize human white blood cells in blood for up to 4 weeks. After HIV infection of the animals, we will determine whether this mouse model can recapitulate many of the hallmarks of HIV infection in humans, such as profound T cell infection and death in the blood. We will also use this model to understand how HIV spreads from one part of the body to another. Taken together, we will develop a white blood cell transplantation mouse model to study the biology of human white blood cells, and how these behaviors are altered during HIV infection. In future studies, we will further develop these animal models to study other blood-borne pathogens.

Project ID: 2020.019

Title: Immune responses against cytomegalovirus 

Project Approval Date: 2020-03-31 

City: Windsor

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transplantation medicine

Summary: In this project we study the innate immune responses against cytomegalovirus (CMV) infection in healthy humans. Approximately, 40-70 of the population is latently infected with CMV. However, this virus can cause severe disease and complications in immunocompromised patients. The immune system of a healthy individual is very effective in preventing CMV disease. A type of white blood cell called the natural kill (NK) cells are particularly important in immunity against this virus. NK cells seek out and destroy virus infected cells. This is performed with the help of proteins called receptors found on the surface of the NK cells. Depending on the type of receptors present on the surface of NK cells, they can either provide immunity against CMV or be inhibited by the virus. CMV infection also causes changes in NK cell receptor composition to influence its activity. We seek to understand how receptors are modulated during CMV infection and which receptors are important for NK cell function to provide immunity against this virus. For this project we analyze NK cells isolated from blood of healthy donors. NK cell receptors and their activity will be compared between CMV-positive (latent infection) and CMV-negative (uninfected) individual. These studies will advance our understanding of how NK cells provide immunity against CMV and which receptors are important for this function of NK cells.

Project ID: 2020.031

Title: Internal validation studies for Serological Assays For anti-SARS-Cov2 antibodies 

Project Approval Date: 2020-06-23 

City: Richmond

Type of Organization: Industry 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: Pro-Lab is developing a blood test to determine if people have been exposed to Covid-19 by detecting antibodies that have developed to the virus in patient/donor blood. The donor samples will be used throughout the internal validation and quality control studies on Latex agglutination, ELISA and Lateral flow assays to ensure assay performance optimization.

Project ID: 2020.032

Title: Design and testing of new cellular therapies for cancer 

Project Approval Date: 2020-07-23 

City: Vancouver

Type of Organization: Academic 

Use of Animals: Yes

Canadian Blood Services Mandate: Transplantation medicine

Summary: Adoptive immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, is a new treatment approach that has been shown to induce deep remission in patients with a variety of blood cancers.  These therapies are manufactured by isolating patient immune cells, genetically modifying them to recognize the tumour cells, expanding them to high numbers, then infusing them back into the patient to achieve deep cancer remissions. This study aims to 1) aid in the development of new immune cellular therapies and 2) determine the optimal timing and manufacturing processes used to produce highly effective and safe cell therapies.  As these therapies are manufactured using human immune (blood) cells, donated blood products are essential for the development of these therapies. So far the study has focused on testing new CAR-T cell therapy products for multiple myeloma and the results will soon be presented at an upcoming international myeloma society (IMS) meeting.  The study is also exploring ways of making more durable (persistent) CAR-T cell therapy products through more sophisticated manufacturing processes. It is expected that new, more effective, CAR-T cell therapies will be identified in this study and these new cell therapy products will improve patient outcomes across a variety of blood cancers.

Project ID: 2020.038

Title: Regulation of immune responses in transplantation and autoimmunity 

Project Approval Date: 2020-09-08 

City: Vancouver

Use of Animals: Yes

Canadian Blood Services Mandate: Transplantation medicine

Summary: Transplantation is used to treat end-stage organ failure, as well as cancers or other deficiencies of the immune system. In order for bodies to accept transplanted cells or organs, patients must take powerful immunosuppressive drugs for the rest of their lives. These drugs have many side effects and often do not effectively stop the immune responses that lead to transplant failure. Our lab is studying how a specialized type of white blood cell known as a T regulatory cell, or Treg, turns the immune system off. The normal function of Tregs is to prevent autoimmunity. We aim to learn how to harness the protective properties of Tregs so that they can be used as a therapy to prevent the undesired immune responses that cause transplant failure and/or autoimmunity. The goal is to find ways to track and manipulate Tregs therapeutically so that the need for transplants would be reduced (i.e. by decreasing autoimmunity which leads to end stage organ failure) as well as the need for life-long immunosuppressive drugs in patients who received a transplant. Overall the research will lead to the development of improved outcomes for patients who need, or who have had, a transplant.In the past year, discoveries which were made possible by the use of CBS blood products included:-Discovered that removal of a signalling protein known as PTEN can increase the effectiveness of Treg therapy -Found that assessing expression of a protein known as Helios is important for determining the purity of a Treg cell therapy product -Published our method on how to measure the ability of Tregs to suppress antigen presenting cells so that other investigators can easily use this assay in their studies.

Project ID: 2020.044

Title: Image based cell separation 

Project Approval Date: 2020-09-09 

City: Vancouver

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transplantation medicine

Summary: The purpose of this study is to develop methods for cell separation based on microscopy images. Immunophenotyping is an expensive and error-prone process, despite significant efforts in standardizing staining, data collection and automation of analysis. Also, morphological differences between cells may not need to be apparent to the naked eye in order to be sufficient for cell classification. Consequently, we will develop an approach for using disaggregated cells, similar to the preparation employed in standard laboratory flow cytometry, to establish rapid and robust image-based cell phenotyping of cells. With this capability, it might be possible to develop a model for the 200+ known cell types in the human body in order to detect previously unknown phenotypes or detect phenotypic shifts that occur because of disease or treatment. Immune cells will be separated from whole blood and stained with a variety of fluorescent markers. We will assess the cell images and develop tools in order to predict cell phenotype and function. Finally, cells will be separated based on their phenotype and function from the microscopy images. We have developed a technology to separate cells based on microscopy using micropatterning of photo-reactive hydrogels to selectively retain unwanted cells in a microwell plate, which enable the extraction of target cells by simple pipetting. Our process is high-throughput and insensitive to cell type. 

Project ID: 2020.047

Title: Harnessing immune cells to improve stem cell transplant outcomes 

Project Approval Date: 2020-10-01

City: Toronto

Type of Organization: Academic 

Use of Animals: Yes

Canadian Blood Services Mandate: Transplantation medicine

Summary: Graft-versus host disease (GVHD) following stem cell transplant is often a major limitation to the success of this therapy for treating blood cancers. Stem cell transplant can be curative, but 30-80% of patients develop acute GVHD within the first 100 days of transplant.1 While 30% of patients fail to respond to the current therapies, this study addresses discovering new therapeutic options for acute GVHD patients.

Project ID: 2020.051

Title: T cell isolation from CBS products 

Project Approval Date: 2020-11-04 

City: Vancouver

Type or Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transplantation medicine

Summary: We investigate human embryonic and T cells in culture, for research purposes only and with no humans involved (besides the Canadian Blood Services source of the blood cells and the embryonic stem cell derivations that were done by other labs a long time ago). Our work is mainly on developing the best ways to culture these cells, to produce desired therapeutic cell types.

Project ID: 2020.052

Title: Optimization of Regulatory NK cell expansion for therapy of cGvHD

Project Approval Date: 2020-12-15 

City: Vancouver

Type of Organization: Academic 

Use of Animals: Yes

Canadian Blood Services Mandate: Transfusion and Transplantation medicine

Summary: Hematopoietic Stem Cell Transplantation (HSCT), the infusion of a donors immune system into a recipient, is an important immune-based therapy for patients with high-risk and recurring blood cancers. However, HSCT is attributed to an increased risk of health complications, the most severe being chronic graft-versus-host-disease (cGvHD), in which foreign donor immune cells attack the recipient’s tissues. cGvHD occurs in 25% of pediatric and 60% of adult HSCT survivors. It is known to cause long-term, and often irreversible organ damage and has a 10-25% mortality rate. Our team has identified an increased number of a rare peripheral immune cell population, known as regulatory Natural Killer cells (NKreg), in transplant patients who failed to develop cGvHD. Further, other researchers have found that the transfer of expanded NK cells potentially decreases blood cancer relapse with no increase in GvHD. Thus, we hypothesize that the transfer of expanded NKreg cells after transplant represents a significant strategy to decrease cGvHD without increasing blood cancer relapse.To address our hypothesis, we have been pursuing three aims. First, we have been determiningthe function of NKreg cells associated with successful and failed suppression of cGvHD. Second, we have been optimizing the expansion of functional NKreg cells appropriate forhuman clinical trial. Third, we will evaluate the effect of expanded NKreg cells on cGvHD immune populations in both culture and mouse models.

Project ID: 2020.057

Title: Studying the genes controlled by MTF2 in blood cells 

Project Approval Date: 2021-01-13 

City: Ottawa

Type of Organization: Academic 

Use of Animals: Yes

Canadian Blood Services Mandate: Transplantation medicine

Summary: The goal of our research is to understand the role of MTF2 in blood cells. MTF2 is part of a protein complex that controls whether of some genes are turned on of off in blood cells. When MTF2 is not properly functioning in leukemia cells, we discovered that it is not able to properly control the expression certain genes. This results in  genes being abnormally turned on, which in turn prevents the leukemia cells from responding to chemotherapy treatment. Using cord blood cells obtained from CBS, we demonstrated that using drugs to block a gene called MDM2, which is abnormally turned on, can help leukemia cells respond to chemotherapy. This idea is being tested in a clinical trial to help leukemia patients respond better to standard chemotherapy. We will continue to characterize the genes controlled by MTF2 to understand the function of the genes in blood cell development and leukemia. The results of these studies will advance our knowledge about the normal and abnormal development of blood cells that may be applied to developing new effective therapies to treat leukemia.

Project ID: 2020.058

Title: Medical Laboratory Technology Science Diploma Program College of New Caledonia 

Project Approval Date: 2020-12-17 

City: Prince George

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transplantation medicine

Summary: This project supports the training of medical lab technologists in the field of transfusion science by providing experience for students in the Medical Laboratory Technology Science Program at the College of New Caledonia. Each student interacts with the blood and blood products from CBS during laboratory training and practice activities. These interactions help students to develop a foundation of skills, behaviours and attitudes that are essential for student progress to clinical training in hospital laboratories and transfusion departments. This experiential learning is essential to student development and is superior to the study of images and theoretical knowledge alone. The MLTS program orders packed red blood cells and occasionally frozen plasma to stock the CNC MLTS laboratory each semester.

Project ID: 2020.059

Title: Epigenome-wide CRISPR Screen in Primary Human CD8+ T Cells

Project Approval Date: 2020-12-11 

City: Toronto

Type of Organization: Academic 

Use of Animals: Yes

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: Objective: To identify novel epigenetic modulators of human CD8+ T cell function.

Current progress: Through pooled lentiviral CRISPR screen in primary human CD8+ T Cells, we have identified novel regulators of T cell function. Our immediate steps are to validate these targets that positively regulate CD8+ T cell proliferation, activation and cytolytic function.

Significance: Results obtained in this study will identify new therapeutic avenues to enhance T cell function through epigenetic modulation. Given that studies are performed in human T cells, the results have the potential to be incorporated into adoptive transfer of engineered T cells into patients. In addition, to fostering scientific collaborations in Toronto, Ontario; scientific discoveries generated from this study have the potential in to be used as treatment for hematological and solid cancers by harnessing the immune system.

Project ID: 2021.003

Title: New method of kidney preservation with blood at room temperature to improve transplant success 

Project Approval Date: 2020-12-11 

City: London

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transplantation Medicine

Summary: Transplantation improves the quality of life and survival of patients at a much lower cost than dialysis. However, only 40% of patients receive functional kidneys due to a lack of living organ donors. To increase the number of kidneys available for transplantation, surgeons are accepting organs from deceased donors. These kidneys are commonly stored in cold solution without oxygen. As a result, organs suffer injuries. Therefore, we need to develop a new method to preserve donated kidneys that address these issues. Our objective is to study the effects of a blood on storing human donor kidneys for long periods of time (16 hours) at room temperature. We will also evaluate if certain drugs can maximize the preservation of these organs. Our main goal is to properly preserve kidneys coming from dead donors, to extend their lifetime after transplantation and to improve the quality of life of patients while reducing the cost of transplantation worldwide. 

Project ID: 2021.005 

Title: UCAN CAN-DU: Canada-Netherlands Personalized Medicine Network in Childhood Arthritis and Rheumatic Diseases 

Project Approval Date: 2021-02-02 

City: Toronto 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: Childhood arthritis describes a group of diseases that commonly present as pain, stiffness and swelling of the joints and other supporting structures of the body. Providing timely and effective interventions is crucial for improving health outcomes for children living with this disease.One of the challenges when it comes to treating childhood arthritis is providing the correct treatment at the opportune time. While advanced biologic therapies can be highly effective, we’re currently unable to accurately predict which children should start biologic therapies and which can discontinue treatment without having disease flares. The overarching goal of the UCAN CAN-DU study is to address this gap in treatment approaches and support translational research for all children with juvenile arthritis.

We propose to combine multiple data types – clinical and biologic data - to identify biomarkers that can provide diagnostic and prognostic information to caregivers at the bedside. We will develop separate profiles of biomarkers to predict disease course, treatment response and risk of disease relapse. Biomarker profiling will be done on circulating white blood cells  isolated from whole blood, as well as from serum and plasma from patients.  Circulating white blood cells, plasma and serum derived from healthy donors will be used as reference/control. 

Project ID: 2021.007

Title: Using molecular biology to increase the lifespan of platelets 

Project Approval Date: 2021-03-09 

City: Vancouver

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transfusion Medicine

Summary: Platelets are an integral part of blood clotting, and used clinically to manage bleeding in patients suffering from a number of diseases. The short shelf life of platelets remains a major challenge in the management of platelet products. This project asks whether new tools for delivering non-native proteins and genetic material to platelets using state-of-the-art-lipid particles will lead to a new understanding of the processes that affect platelet activity during storage, and whether these tools can lead to modified platelet products. The long-term objective of this project is to improve the therapeutic capabilities and shelf life of existing platelet products by treatment with our lipid particles, reducing the demand on the current platelet product supply. This goal is directly in line with the Canadian Blood Services mandate to advance transfusion science.

Project ID: 2021.008

Title: Better understanding Osteoarthritis 

Project Approval Date: 2021-02-19 

City: Toronto

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: Osteoarthritis is a condition that affects millions of Canadians and that is a slow, gradual wearing down of tissue and bone that affects the movement and flexibility in your joints. As you get older, it is possible to develop osteoarthritis in your knees and other parts of your body. Presently, it can be difficult to determine how severe the condition is or how it will progress simply by evaluating symptoms and medical imaging alone. Currently, there is no highly effective clinical treatments or cures for this disease.The purpose of this study is to discover the effects of arthritis on the biology of cells, and the role of inflammation in osteoarthritis. Healthy samples are needed to be used as a ‘control’ or comparison with the arthritis samples in this study.We also want to find out if these blood cells can increase the effectiveness of cells found in the bone marrow (mesenchymal stromal cells) because these bone marrow cells can be used as a treatment for arthritis.

Project ID: 2021.013

Title: Deep Supercooling of Red Blood Cells 

Project Approval Date: 2021-03-24 

City: Edmonton

Type of Organization: Academic and Canadian Blood Services 

Use of Animals: No

Canadian Blood Services Mandate: Transfusion and Transplantation Medicine

Summary: Red blood cells (RBCs) are possibly the most transfused blood component and the most widely stored cell type. While cold storage (+4 C) of RBCs has been vastly improved in the last few decades with a standard storage time of 42 days in clinical settings, recent clinical retrospective as well as laboratory studies indicate that storage in excess of 14 days may alter the biochemical properties of RBCs and lead to inferior outcomes in patients. Here, we propose to develop an RBC preservation method based on our recent breakthrough in deep supercooling of aqueous solutions where we can achieve seemingly stable supercooling for large volumes stored at low temperatures (down to -20 C) for long periods of time. Our eventual goal, by combining our deep supercooling approach with other advances in RBC storage, is to extend the acceptable storage period to a minimum of 100 days. This would relieve logistical constraints, reduce waste of donated blood, and alleviate concerns related to use of aged cold-stored RBCs. 

Project ID: 2021.014

Title: Amplification and Enrichment Platforms for Liquid Biopsy-based Cancer Detection 

Project Approval Date: 2021-04-15 

City: Edmonton

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: There is an urgent unmet need for non-invasive, simple, but reliable tests to not only detect cancer at an early stage but to also estimate how aggressive the cancer may be. Such early prognostication would provide doctors important information to balance watch-and-wait paradigms with aggressive treatment strategies that may carry risks. Biopsies and pathology are the gold-standard but biopsies cannot be done too often, and there is considerable patient resistance to such procedures. As such,we aim to develop novel strategies for early prognostication of cancer from liquid biopsies. Blood tests have been widely researched but few blood biomarkers have early prognostic value. Circulating tumor cells (CTCs) have considerable prognostic value but are extremely sparse. We propose early prognostication using strategies to significantly amplify blood biomarker levels to enrich CTCs and other blood bourne markers such as mRNAs for analysis.We would like to acquire blood samples from CBS to identify baseline expression levels of various bloodbourne biomarkers to assess their relative utility in our liquid biopsy assays. 

Project ID: 2021.017

Title: Translational study of the Pyoderma gangrenosum biomarkers 

Project Approval Date: 2021-05-06 

City: Toronto

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: Neutrophilic dermatosis are typically painful, acute-on-chronic inflammatory skin diseases presentingwith recurrent pustules and abscesses, leading to scarring and permanent disfigurement. The quality of life in the patients with such diseases, like Hidredinitis Supparitiva (HS) and Pyoderma Gangrenosum (PG) are severely impacted as result of the chronic pain, odorous discharge and disfigurement. The underlying etiology of of these inflammatory diseases are presently unknown and current treatment is often inadequate or ineffective. It is critical to our understanding of pathogenesis of disease progression of neutrophilic dermatoses to identify biomarkers in both skin and blood, in order to develop targeted treatments, and ultimately a cure. Currently, there are drugs being developed to interfere with the hypothesised immunological mechanism underlying HS and PG. We will evaluate the effect of the newly generated drug family of IRAK4 degraders, as well as other therapeutic interventions, as a novel targeted therapeutic for the treatment for these diseases. The finding of this study will enable us to identify the biomarkers in HS disease and the efficacy of therapeutic intervention and ultimately find a cure. 

Project ID: 2021.019

Title: Developing methods to standardize blood tests for neurological diseases 

Project Approval Date: 2021-07-07 

City: Vancouver

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: Early disease diagnosis is important for effective treatment, and for determining who can take part in trials for new treatments. This has been a major challenge in the field of neurological disease, notably for cases of dementia, brain injury, and spinal cord injury, where most clinical ​procedures involve using expensive imaging techniques. Emerging tools for early disease diagnosis include the use of “biomarkers”, which are disease-specific molecules in the body that can be detected in blood. Biomarkers are the focus of many research groups in developing simple and low-cost blood tests for disease diagnosis. However, there is a challenge in not only determining which biomarkers reflect these diseases best, but also determining how to measure them accurately so that they can be used in the future as diagnostic tools in the clinic. This project will prepare pooled blood samples from individual donors, collected by Canadian Blood Services, to create reference materials. These materials will be sent out to other laboratories to check specificity and reproducibility of new blood tests being developed for dementia, brain injury, and spinal cord injury, before they enter the clinic, and will become part of an international quality control program for neurological blood biomarkers.

Project ID: 2021.030

Title: Development of human antibodies against SARS-CoV-2 using human B-cells 

Project Approval Date: 2021-09-09 

City: Ralston

Type of Organization: Government 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: The impact of COVID-19 pandemic is horrifying and unprecedented. It is likely that the pandemic might not end any time soon due to the emergence of more and more SARS-CoV-2 variants all over the world. It is therefore imperative to rapidly develop, in parallel to vaccines, therapeutics against SARS-CoV-2 and its variants to fight the pandemic. Human monoclonal antibodies (mAbs) are safe and ideal therapeutics and most importantly, human mAbs can be rapidly developed to treat infectious diseases from the blood of convalescent or vaccinated donors. Current antibody therapies are usually administered intravenously due to the large amount of antibody required. The high dosage results in high cost and intravenous infusion, which requires hospital settings, making the mAb therapy hard be accessible by the developing countries. To solve this issue, it is desirable to develop highly potent human mAbs with lower dosages required, which will lead to cost reduction and being deliverable via intramuscular or subcutaneous injections. To this end, in this proposal, single memory B cells, which have undergone somatic mutations so as to secrete high-affinity SARS-CoV-2 spike protein-specific antibodies, in human blood samples from SARS- CoV-2 convalescent or vaccinated donors will be isolated through a series of separation steps, including memory B-cells enrichment, single memory B-cell sorting, selection of single memory B-cells secreting highly potent anti-SARS-CoV-2 antibodies by neutralization assay, PCR amplification of antibody genes from the selected single memory B cells. Lastly the amplified antibody genes will be expressed in mammalian expression system and then the recombinant human antibodies characterized.

Project ID: 2021.033

Title: Identification of plasma exosomal biomarkers in normal regenerated liver 

Project Approval Date: 2021-10-06 

City: Toronto

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transplantation Medicine

Summary: The liver is the only visceral organ in the body with a rapid regenerative capacity. Understanding the mechanisms that help regenerate the liver is critical to repairing the damaged liver in patients with liver failure. To better understand how normal liver regeneration occurs and how we can distinguish normal versus abnormal regeneration, we will examine in this study both liver and plasma samples undergoing regeneration. We have selected liver biopsy specimens identified as normal regeneration within the 3 first months following liver transplant, and we will request the retrieval of plasma samples that are matched or unmatched with these liver biopsies from the UHN Biobank. Liver biopsies have been used to characterize different cell types in the regeneration process and their molecular signatures, while the plasma will be used to extract exosomes, and identify particular circulating gene markers. We will process to the comparison of circulating markers of normal regeneration, defective regeneration (plasma from cirrhotic liver patients), and healthy controls (plasma of blood donors from Canadian Blood Services). In the prospective study, we will collect blood from both liver donors and liver transplant recipients to investigate the regeneration activity following hepatectomy and liver transplant. 

Project ID: 2021.037

Title: Understanding the role of extracellular vesicles released from naive and malaria infected red blood cells 

Project Approval Date: 2022-04-01 

City: Ste. Anne de Bellevue

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Transfusion Medicine

Summary: The blood stages of Plasmodium falciparum parasites cause the pathology associated with malaria. Extracellular vesicles (EVs) are small, membrane-bound particles that have been implicated in the biomolecular mechanisms by which P. falciparum potentiates malaria pathology and may also use EVs to promote its survival within the human host. Naïve and P. falciparum-infected erythrocytes release different EV subpopulations depending on the age of the erythrocytes and the intraerythrocytic life stage of the parasite. These subpopulations may further comprise different EV subtypes according to their size (small, medium, large) and/or biogenesis. Functional studies have shown that different EV subpopulations and subtypes target different host cells and effect specific functions within these target cells, which include immune cells, endothelial cells, and other erythrocytes. As with all EVs, P. falciparum-infected erythrocyte-derived EVs mediate intercellular communication through their biomolecular cargo that includes nucleic acids, proteins, and lipids. We hypothesize that the target cell specificity of EV subpopulations and subtypes is determined by their biochemical cargo. This study will identify the biochemical distinctions and/or commonalities of EVs released from naïve, and ring, trophozoite and schizont-infected erythrocytes. These findings will provide insights into the biogenesis, target cell specificity and functions of the different EV subpopulations and subtypes.

Project ID: 2021.041

Title: Release of already collected plasma from donors infected with COVID-19 

Project Approval Date: 2023-09-18

City: Vancouver

Type of Organization: Government 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: The COVID-19 pandemic continues to be a public health emergency in Canada and around the world. The emergence of novel COVID-19 variants means that researchers must continue to develop novel assays for the detection and quantification of SARS-CoV-2, the virus that causes COVID-19. The overall goal of this project is to source convalescent plasma from donors infected with SARS-CoV-2 variants of concern (VOCs), variants of interest (VOIs), and other variant strains of importance. The convalescent plasma will be used to to support a global program to construct standards and panels for serologic assays and especially assays designed to look at differentiation and quantitation of, as well as antibody response to, SARS-CoV-2 variants.  This study is conducted in collaboration with public health officials at the BC Center for Disease Control, Vitalant Research Institute, and Duke Human Vaccine Institute.

Project ID: 2021.046

Title: Modified Platelet Storage Devices to Improve Quality During Storage 

Project Approval Date: 2022-03-09 

City: Vancouver

Type of Organization: Academic and Canadian Blood Services 

Use of Animals: No

Canadian Blood Services Mandate: Transfusion Medicine

Summary: Platelets are the blood cells which are responsible for forming blood clots. Platelet transfusion is a lifesaving treatment for bleeding, such as on the battlefield or on automobile accidents, and is an important therapy for certain blood disorders and chemotherapy. Platelets have short shelf-lives because their current storage bags tend to activate them, leading to rapid clearance and poor transfusion outcomes. Furthermore, the stored cells can be easily contaminated by bacteria, which leads to severe sickness and platelet wastage. This project aims to develop platelet storage bags which extend the shelf-life of these cells and prevents bacterial colonization. We will screen a list of different coating materials to devise a formulation which most optimally extends platelet shelf life while being hostile to bacteria. We will then implement this coating into our bags and assess the short- and long-term effects of storage on the cells. Successfully extending the viability and protecting the quality of platelets will improve the outcome of their transfusion, directly saving the lives of recipients. This project may also save millions of tax payer dollars in the long run by limiting wastage of platelets due to expiration and contamination.

Project ID: 2021.047

Title: Natural killer cells in cancer and immune homeostasis: a focus on diverse function 

Project Approval Date: 2022-02-03 

City: Halifax

Type of Organization: Academic 

Use of Animals: Yes

Canadian Blood Services Mandate: Transplantation Medicine

Summary: NK cells can be directed to control cancer and other diseases.Our research focuses on a type of white blood cell, called natural killer (NK) cells. NK cells are poorly understood because they are complicated, and the genes that control their function are variable between people. Still, it is known that NK cells can directly detect and kill cancer cells, or infected cells, while also directing other immune cells to help. For these reasons, we think it is important to better understand both the genetics and functions of NK cells.  

NK cells are already being targeted or used in clinical trials. They can be expanded virtually limitlessly and adoptively transferred between people without causing damage to healthy tissues, or they can be guided by antibody and other therapies that control their function. Still, studies have not yet considered how the different features of NK cells factor into their activity against each person’s disease. Likely as a result, the outcomes of clinical trials have been variable. Our research goals are to understand how the genetics and phenotypes of NK cells predict their functions for direct killing and polarizing immune responses. Understood, this will inform how NK cells can be directed to control cancer and other diseases. 

In particular, we are interested in two gene families that have the most control over NK cell function: the Killer Immunoglobulin-like receptors (KIR) and their ligands, groups of human leukocyte antigens (HLA). NK cells use these KIR proteins to engage with conserved ligands that are found on groups of HLA molecules, so we measure only these ligands (not specific HLA alleles). In patients undergoing bone marrow transplantation or hematopoietic stem cell transplantation, where HLA alleles are matched between donors and recipients, it is already known that the donor’s KIR genes (which are on a separate chromosome from HLA and need not be matched) predict for cancer relapse or control. We think that NK cells’ KIR genes likewise have impacts on NK cell function in adoptive transfer of mature cells. Hence, our work is important to Canadian Blood Services in that it may inform immunotherapies, including stem cell transplantation and in the future, adoptive cell therapies. 

Project ID: 2022.003

Title: Effect of HIV drugs on Immune Response 

Project Approval Date: 2022-02-25 

City: Vancouver

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: People who have HIV require lifelong treatment with HIV medications, and although of these are good at controlling the virus, but have side effects that may hurt the cells in our body. We believe that some HIV medications can impede the immune system, and its ability to respond to pathogens. We want to study HIV medications to see if they prevent our immune cells from doing their job. It is important to know this, as HIV treatment is lifelong, and choosing the safer medications is important for people’s health and for vaccines to work. To do this research, we require a large quantity of blood cells, because we need to test the effects of five different HIV medications, daily, over 12 days. We will use the donated blood from Canadian Blood Services to isolate the immune cells, and treat them with HIV medications . Afterwards, we will look for any damage the cells have sustained, and any delay in their immune response. This is only possible with the help of Canadian Blood Services because all drugs must be tested on the same donor, and this requires a high blood volume. This research will benefit all people living with HIV.

Project ID: 2022.006 

Title: Characterization leukemia interactions with the immune system to identify novel therapies for relapsed/refractory disease 

Project Approval Date: 2023-06-16 

City: Toronto 

Type of Organization: Academic 

Use of Animals: Yes 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: Leukemia is a common and devastating pediatric and adult malignancy. Novel treatments for a subset of patients with relapsed/refractory T cell disease are almost non-existant. Unlike patients with B cell leukemia who have benefitted from immune system targeted therapies, these treatments are still unavailable to patients with T cell leukemia. We hypothesize that, similar to other cancers, leukemic T cells suppress anti-tumor immune responses in diseased tissue, including the bone marrow, the tissue that generates healthy blood and immune cells. Our lab is performing single-cell RNA-sequencing of healthy and diseased bone marrow to identify how T cell leukemia interacts with immune cells in this tissue. We found that immune cells from diseased, but not healthy, bone marrow express markers of immune exhaustion suggesting that leukemic cells are suppressing an anti-tumor immune response. Additionally, we identified several immunosuppressive ligands upregulated on leukemic cells that are known immunotherapy targets in other cancers. Next, we plan to interrogate expression of T cell exhaustion markers, such as LAG3 and CTLA4, on T cells from healthy donor and primary T-ALL blood samples, as well as immunosuppressive ligands on healthy donor blood and CD34+ hematopoietic stem cells. This analysis will allow us to determine if markers of immune exhaustion are found on circulating immune cells from leukemia patients. Furthermore, analysis of immunosuppressive ligand expression on CD34+ hematopoietic stem cells will allow us to identify the potential for on-target off-cancer effects of immunotherapies. Identification of markers of immune exhaustion on blood immune cells from leukemia patients but not CBS donor healthy immune cells could provide valuable diagnostic information concerning the immunosuppressive landscape of the bone marrow in leukemia patients.This study will characterize the leukemia immune microenvironment and identify targets for immunotherapeutic intervention for patients with treatment refractory leukemia to improve outcomes. 
Our research seeks to identify new immune cell therapies for children and adults with leukemia. Our work is in line with the blood products for research goal of providing primary samples for investigators to promote advances in the field of cellular therapy. 

Project ID: 2022.007 

Title: Development of novel methods to detect immune responses to viral infections and vaccination 

Project Approval Date: 2022-07-18 

City: Toronto 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: We recently described a method to detect antibodies against SARS-CoV-2 by monitoring COVID-19 antigens in human plasma samples from Canadian health care workers and COVID-19 vulnerable populations prior to and following vaccination. Development of such a humoral immune profiling platform helps to ensure that Canadians have the ability to rapidly detect newly acquired infections caused by novel pathogens like SARS-CoV-2. To date, this method has been used to measure antibody levels in >120,000 unique plasma, serum, or dried blood samples from multiple studies. This methodology relies on controls to help set and calibrate positivity thresholds thus enabling the measurement of antibody levels against Spike, its receptor binding domain (RBD), and the Nucleocapsid (N) protein. To mitigate concerns regarding sensitivity and specificity of the assay and enable standardization we must use control samples with known antibody levels as reference and we need high volumes of plasma to standardize the assay across studies. We hypothesize that by using convalescent plasma from Canadian Blood Services (CBS) donors who have recovered from a recent bona fide infection (with high levels of all three Spike, RBD, and N antibodies), we will be able to calibrate our assays for measuring unknown sample antibody levels. CBS blood for research program is a promising resource for high volumes of such rare samples. A robust quality control platform will help us to produce better quality data and ensure the highest quality knowledge is used to form health policy guidance. We have previously worked with Steve Drews at Canadian Blood Services on a seroprevalence study of CBS donors.  Similar to CBS, we are actively working on large national studies with the Canadian COVID-19 Immunity Task Force (CITF).  By having access to high volume samples for quality control, we can provide higher quality data to CITF which can be used to compare and cross-validate seroprevalence estimates from CBS.  It will also help inform CBS on the overall SARS-CoV-2 antibody levels in the general Canadian population including from those who may donate blood. 

Project ID: 2022.009

Title: Control Sample Preparation for Quality Assurance of Specimen Analysis for the Provincial Newborn Screening Program

Project Approval Date: 2022-03-04 

City: Winnipeg

Type of Organization: Government 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: The request for packed red blood cells and whole blood is not being made with the intent of conducting research, but rather, to use the material in the preparation of an artificial whole blood matrix resembling that of the newborn infant. This will facilitate the preparation of control blood specimens to be used in validating the analytical results of all testing procedures used to screen newborn infants for inherited metabolic diseases, endocrine dysfunction, and SCIDS (Severe Combined Immunodeficiency Syndrome). The Manitoba Newborn Screening program has been in operation for over 50 years improving the lives of newborn infants and continues to be one of the best programs in the country. We request the help of your organization and that of your generous donors, to allow our program to continue to provide high quality service for the newborns of Manitoba by supplying red blood cells and whole blood. Since the current approval for study REB 2017.004 is expiring April 3, 2022, this application is being submitted to allow for continuation of our current Newborn Screening program quality assurance and improvement practices of making the blood control specimens.

Project ID: 2022.014

Title: Effect of blood transfusions in the oxygen affinity of cord blood 

Project Approval Date: 2022-05-18 

City: Calgary

Type of Organization: Academic and Government 

Use of Animals: No

Canadian Blood Services Mandate: Transfusion Medicine

Summary: 

What question are you trying to answer?

Exposure to high oxygen levels is harmful to the preterm infant and contributes to retinopathy of prematurity (ROP), a retinal disease that can result in blindness. ROP affects approximately 120 babies per year in Calgary. Several studies have found a marked increase in the occurrence of ROP following blood transfusions though the cause is not clear.

Adult packed red blood cells (pRBC) in transfused blood bind oxygen less tightly than fetal red blood cells present in the preterm infant.

Therefore, a newborn maintained at the same oxygen saturation, which reflects bound oxygen, would be expected to have more unbound oxygen (PaO2) following a pRBC transfusion.

In clinical practice, we use continuous oxygen saturation (SaO2) as a surrogate marker of oxygenation. However, the PaO2 is the more physiologically relevant variable as it reflects the oxygen that is freely available to the cells.

How will the answer to your question help your research field?

Quantifying the shift in oxygen binding following red blood cell transfusions is an important first step in eventually customizing SaO2 targets for each infant based on their blood’s oxygen binding properties and transfusion needs. We will use information from this study to design a future randomized control trial examining the effects of adjusting SaO2 targets following blood transfusions on reducing the incidence and severity of ROP. 

Project ID: 2022.020

Title: Immune Sensing of RNA Formulations using Human PBMCs 

Project Approval Date: 2023-02-27 

City: Vancouver

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: With the successful development of messenger ribonucleic acid (mRNA) vaccines against COVID-19, the field of RNA therapeutics has evolved. Due to the instability of RNA, these molecules require a vehicle for delivery to the cells in the human body and the current leading candidates for such deliveries include polymeric vehicles, lipid-nanoparticles, and nanoemulsions. In the context of vaccine development, there is evidence that these vehicles provoke an immune response but the exact mechanisms are unknown. This project will use human peripheral blood mononuclear cells (PBMC) from whole blood to explore the human immune responses to these delivery systems. We hypothesize that using human PBMCs as a model system to study innate immune cellular pathways involved in recognizing and processing the vehicle-RNA-loading complexes would lead to improved formulations of the current RNA-based vaccines, improved clinical translatability of RNA delivery vehicles and eventually the development of RNA delivery vehicles based on therapeutic needs. The specific objective of this project is to gain a preliminary understanding of cellular pathways involved in recognizing and processing vehicle-RNA-loading complexes in immune cells. Once we have gained some understanding of the relevant pathways, we will begin altering our formulations to allow more effective delivery of therapeutic RNAs.

Project ID: 2022.021

Title: Designing better materials for the body 

Project Approval Date: 2022-07-214

City: Edmonton 

Type of Organization: Academic

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: Molecular self-assembly of peptides is proving to be a powerful technique for forming novel materials that allow the incorporation of biofunctional motifs into complex nanostructures that are formed using benign assembly processes. In particular, the ion-complementary self-assembling peptide RADARADARADARADA (RADA4, type 1: -+;II:--++) has been shown to self-assemble into nanofibers that subsequently develop into a viscoelastic 3D matrix in aqueous solution. Recent work indicates that RADA4 may provide a robust nanomedicine platform, with traits ideal for soft-tissue applications: peptide sequence programmability, non-cytotoxic, elicit a minimal inflammatory response (mechanism unknown), applicable to non-invasive therapies, in situ gelation, 3-D cellular activities, localized drug delivery, and an internal hydration of up to 99.5% w/v water. Plasma protein interactions with foreign surfaces is the fate determining step that dictates the application of implant biomaterials, no previous work could be found that discussed the interaction between peptide self-assembled materials and plasma proteins. Moreover, there are very few studies that have attempted to correlate the physicochemical properties of peptide based materials to protein adsorption (denaturation, activation) that is so critical to a myriad of deleterious host responses (thrombosis, inflammation, etc.).Therefore, this research program will focus upon elucidating the fundamental effects of the amino acid content of self-assembling peptides on plasma protein interactions (adsorption, denaturation, activation) as well as platelet responses. It is thought that this information is of fundamental importance for understanding the molecular level mechanisms responsible for initiation of deleterious host responses to foreign materials, and may provide the 'design criteria' required for further advances in biomaterial development. 

Project ID: 2022.025 

Title: Receptor of activated protein C kinase 1 regulates proteasome activity 

Project Approval Date: 2022-07-26 

City: Halifax 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: Balancing protein production and degradation is crucial for cellular health. Disruption of such balance is connected to many diseases, including autoimmune, neurodegenerative diseases, cardiac dysfunction, cancer, and viral infections. Proteasome is one of the main protein complexes driving protein degradation in cells. Therefore, alteration of proteasome function has great therapeutic potential for treating multiple diseases. The development of such approaches requires a thorough understanding of how the proteasome functions in cells. Our lab discovered that a protein called RACK1 binds to the proteasome and alters its activity. The goal of this research is to determine how RACK1 controls proteasome function via their interaction. Red blood cells have been used as a proteasome source in several studies. Therefore, proteasomes will be purified from human red blood cells obtained via Canadian Blood Services. RACK1 will be expressed and purified from bacteria. The purified proteasome and RACK1 will be subjected to cryogenic-electron-microscopy to determine where the two proteins interact. This information is essential for determining how proteasome function changes with or without RACK1 binding in cells. The outcome of this study is to provide new mechanistic insight to help guide the future development of therapies that alter proteasome activity to treat different diseases. 

Project ID: 2022.028 

Title: Engineering Immune Cell-Based Cancer Therapy 

Project Approval Date: 2022-09-09 

City: Toronto 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: Immune-based adoptive cellular therapies are a promising treatment modality for cancer patients. In its current form, blood-derived T cells are isolated, genetically modified with cancer targeting receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs) and reinfused into patients for treatment. Development of these therapies have relied on the use of human blood from healthy donors who provide the immune cells for genetic modification and testing. The Canadian Blood Services through their Blood4Research program can be a reliable source of human blood for further development of these therapies. Though adoptive cellular therapy against blood cancers has been established, the development of successful therapies targeting solid tumors remains a major obstacle, particularly because highly specific and safe anti-cancer receptors have yet to be found. Recently, we have developed innovative approaches to identify cancer targeting TCRs and CARs. Using these approaches, our proposal seeks to test the ability of these receptors to kill cancer cells using blood derived T cells from healthy donor immune cells. It is hoped that upon completion of this proposal, we will have identified candidate anti-cancer receptors suitable for safe and effective adoptive cellular therapies against cancer. 

Project ID: 2022.032

Title: Understanding how metabolism and immunity control heart disease 

Project Approval Date: 2022-11-28 

City: Ottawa

Type of Organization: Academic 

Use of Animals: No

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services

Summary: Heart disease remains one biggest causes of death and hospitalization in Canada. The build up of plaque in arteries is called atherosclerosis, which occurs over time and is closely linked to risk factors such as obesity, high cholesterol, high blood pressure and smoking. Our research focuses on the cells that form the arterial plaque and how changes in cellular metabolism can cause and potentially help limit the size and severity of the plaque. To study this, we expose cells in a petri dish to the types of factors that they would be exposed to in the body, mainly cholesterol. To do this, we isolate cholesterol from human donor blood and use it to mimic the conditions that lead to atherosclerosis and heart disease. This ability lets us test the importance and potential therapeutic value of different metabolic and immune pathways in cells. 

Project ID: 2022.034 

Title: Factors influencing the survival of red blood cells in circulation 

Project Approval Date: 2022-11-07 

City: Oshawa 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transfusion Medicine 

Summary: Red blood cells (RBCs) are the most numerous cells in our body. However, we now know that they have a specialized cellular machinery that regulates a wide range of their functions. During this period, they are constantly exposed to a variety of environmental challenges such as oxidative stress, which affect their physiological homeostasis. When RBCs fail to counter these stressors, they are injured and are captured by specialized phagocytic cells in the spleen and liver. This feature becomes more prominent in RBCs stored in the blood bank wherein they are increasingly primed to undergo cell death.  The molecular mechanisms underpinning these observations remain unclear. Using a wide array of cellular and molecular biology tools as well as systems biology approaches, our research will examine different signaling networks in RBCs. We will test this by studying their patterns of survival during storage under blood bank as well as in vitro conditions. The basic science knowledge gained from this work will improve our understanding of how RBCs thrive and adapt under different environmental challenges. The results from these studies may have future applications in improving RBC product quality in blood banking.

Project ID: 2022.038 

Title: Neutrophils’ engagement in cancer cells killing 

Project Approval Date: 2022-11-10 

City: Richmond 

Type of Organization: Private Industry 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: Neutrophils-the most abundant leukocytes in the circulation system- are the key players in the modulation of the immune response. The role of neutrophils in the tumour microenvironment (TME) is multifactorial and largely depends on the context. The tumour and other resident immune cells can affect neutrophil polarization towards a pro (N2)- or anti (N1)-tumorigenic role. Thus, the characterization of the neutrophil population within TME and the discovery of the compounds that can engage neutrophils in tumour killing will be beneficial for the broad spectrum of cancer patients. This study aims to obtain a characterization profile of the neutrophil population in the context of various in vitro tumour models. Acquired data can help us develop new therapeutic targets that will provide engagement of neutrophils in anti-tumour response. 

Project ID: 2022.039 

Title: Red Blood Cells for Drug Delivery 

Project Approval Date: 2023-01-10 

City: Hamilton 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: 

In this project we utilize red blood cells to deliver drugs more efficiently and more sustainably to patients. We have already demonstrated the high potential of functionalized red blood cells in several pilot studies. Fighting bacterial contamination and or immunization against Covid-19 were successfully demonstrated and we have developed a suite of advanced methods to manipulate the red blood cells membrane on the nanoscale. We can sensitize red blood cells to specific targets in the human body and produce hybrid cells that can carry different pharmaceutical loads. In the next step, we will expand the application portfolio by incorporating nutrients, anti-cancer drugs and neurological drugs in three projects. Each project goes along with extensive characterization and testing of the synthesized functionalized red blood cells. The donated blood helps to: 

1. optimize our methods to ensure a rapid and personalized synthesis of functionalized red blood cells.  
2. characterize of functionalized erythrocytes to verify size, shape, structure and affinity.  
3. verify the compatibility of different blood groups. 
4. test the synthesized red blood cells using cell-lines.  

The study’s outcomes will benefit the Canadian Blood Services by investigating novel cellular therapies. 

Project ID: 2022.040 

Title: Blood cells surface engineering for cell-based therapies 

Project Approval Date: 2023-01-16 

City: Vancouver 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transfusion Medicine 

Summary: The purpose of the current research proposal is to use chemistry and biomedical engineering tools to develop novel chemical products and methods to address current clinical issues in blood transfusion. To address these needs, we hypothesize that the prevention of immunological rejection of donor blood is of critical importance in transfusion medicine, as unintentional mismatching of red blood cells (RBC) remains one of the most common causes of serious and sometimes fatal adverse reactions. In addition, shortage of blood supply in rare blood transfusion remains a major challenge to our blood bank system as well as for platelets. Also, we are are working on developing new chemical molecules which could prevent rejection of transplanted organs so that patients can survive longer as well as on developing novel polymers coatings with antibacterial and antithrombotic properties for blood bags and catheters.To perform this research, we need fresh human blood and its components so that we can test our new drug molecules and methods before being tested in animals and in humans directly.  

Project ID: 2022.045 

Title: Intra-operative Cell Savage for Pediatric Bone Cancer Surgery 

Project Approval Date: 2023-03-06 

City: Vancouver 

Type of Organization: Academic and BC Children’s Hospital 

Use of Animals: No 

Canadian Blood Services Mandate: Transfusion Medicine 

Summary: This study is about intra-operative cell salvage which is a well-established technique that reduces the need for blood transfusion during surgery. Instead, any blood lost from patients during surgery is collected, washed and returned back to the same patient. Because this technique is not currently standard practice for cancer surgery in children, before we start doing this we want to make sure that it is very safe. To do this, we are doing a study to look at the effectiveness of a special filter at removing cancer cells from the collected blood The first step in the study is to determine how good a test called flow cytometry is at detecting tumour cells in the blood. We will need to use blood from the Canadian Blood Service to do this. We will add specific tumour cells to the blood and then perform a number of the flow cytometry tests to work out the smallest number of cells that can be detected. After we have done this, we will move on to collecting blood from real patients and looking at whether the special filter is able to remove all the cancer cells from the blood. We hope that in the future, after we have proven it is safe, we will be able to use this technique to reduce or eliminate the need for donor blood transfusion. 

Project ID: 2022.046 

Title: Virus-Dependent Changes to Blood Cells and Proteins 

Project Approval Date: 2023-02-03 

City: Vancouver 

Type of Organization: Academic and Canadian Blood Services 

Use of Animals: Yes 

Canadian Blood Services Mandate: Transfusion Medicine 

Summary: Virus-mediated outcomes involve an intricate sequence of events that ultimately culminate in the alteration of host cell processes. Cellular activation is a well-known contributor to disease progression which may be explained in the context of direct virus-cell interactions or virusdependent manipulation of host cell factors. The aim of this study is to therefore answer questions surrounding what happens when a virus encounters circulating blood cells and proteins. This study will help generate knowledge in three key areas. The anticipated results may: (1) help in the understanding of how viruses infect cells; (2) provide insight and ideas into how to maintain blood product safety; and (3) lead to new ways of predicting or treating virus induced pathology. 

Project ID: 2022.048 

Title: Determining Novel Functions of Blood Proteins 

Project Approval Date: 2023-02-03 

City: Vancouver 

Type of Organization: Academic and Canadian Blood Services 

Use of Animals: Yes 

Canadian Blood Services Mandate: Transfusion Medicine 

Summary: The aim of this study is to answer questions surrounding three unique areas of interest. The first project focuses on identifying new roles and uses for well-known molecules involved in blood clot formation that also help to dissolve the clot after it is no longer needed. The second project is working toward understanding how common viruses can use certain clotting molecules to help infect cells. The third project endeavors to learn about normal blood clotting by identifying the specific differences that exist in patients with known blood clotting abnormalities. These studies may lead to new ways of predicting, diagnosing or treating heart disease, help in the understanding of how viruses infect cells, and identify novel genetic alterations that underline coagulation disorders.

Project ID: 2022.049 

Title: Ex Vivo Assessment and Repair of Liver Grafts 

Project Approval Date: 2023-02-21 

City: Toronto 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: Liver transplantation is life-saving for patients with end-stage liver disease or advanced liver cancer. Unfortunately, there are not enough organ donors to meet the demand. Currently, strict criteria are applied to select donor livers. In donors with risk factors for poor liver graft function, the liver is often rejected for transplantation. Being able to assess liver function before the organ is transplanted might allow us to safely use livers which are currently rejected for transplantation. Ex vivo (meaning “outside the body”) assessment of donor livers is a new method to estimate function before exposing patients to excessive risks. In an ex vivo circuit, warm, oxygenated blood and nutrients are circulated through the donor liver for several hours. This is known as ex vivo perfusion. This allows the organ function to be monitored but also may offer the possibility of repairing injured grafts. This basic research study aims to develop a model of ex vivo human liver perfusion, to compare ex vivo liver perfusion with standard cold preservation, and to explore repairing poor or injured livers during ex vivo perfusion. Organs included in this study will have been turned down for transplantation according to current standard criteria and made available for research. None of the organs utilized in this study will be transplanted.

Project ID: 2023.003 

Title: Testing Background Metal and Biomarker Levels in Serum Separator Tubes 

Project Approval Date: 2023-03-15 

City: Calgary 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: Serum separator tubes (SSTs) are used for collection of prenatal blood samples at the Provincial Public Health Laboratory (ProvLab) in Edmonton, Alberta. These samples were sequestered for use in two phases of the Alberta Biomonitoring Program (ABM) and were tested for a suite of environmental chemicals, including metals and cannabis, tobacco, and alcohol biomarkers. These tubes are not recommended for collection of blood to be used for trace metals analysis. The concentrations of metals, cannabis, tobacco, and alcohol biomarkers may have been elevated or reduced because of the use of SSTs. Therefore, it is necessary to evaluate the background levels of the metals and cannabis, tobacco, and alcohol biomarkers in SSTs to determine how the measured concentrations may have been affected. Other tube types recommended by reference labs for collection of blood to be used for these analyses will be used as control tubes. The primary goal is to determine these background levels and determine if the concentrations previously measured in the ABM may need to be adjusted due to the use of these SSTs. The information gained from this study will also be useful for planning future biomonitoring studies that may use blood collected in SSTs. 

Project ID: 2023.005 

Title: To Study Immune Response Against Intracellular Pathogenic Organisms

Project Approval Date: 2023-05-31 

City: Vancouver 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: The Reiner Laboratory studies innate and adaptive immune responses and how these contribute to host resistance to infection.  Macrophages (white blood cells) are the main cells which participate in innate and adaptive immune responses to intracellular pathogens. Ironically, these cells are also target of certain pathogens like TB, HIV and leishmania to find safe haven and responsible for sever morbidity and mortality worldwide. We want to understand their strategies to regulate host cell biology to promote their survival. Understanding these strategies will help us designing novel therapeutics. Currently, we found that intracellular pathogen Leishmania (our model organism) exploits small RNAs of host macrophages to regulate cell biology to their favor. Human white blood cells are needed as host for these intracellular organisms. In addition, this work has direct relevance to transfusion and transplantation medicine where infections are responsible for major morbidities and mortality. This work also focuses on how white blood cells are activated and manipulated, which has implications for tissue rejection in transplant medicine, and autoimmune disorders.

Project ID: 2023.006 

Title: Antitumor immune responses in colorectal cancer 

Project Approval Date: 2023-04-06 

City: Edmonton 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transfusion Medicine 

Summary: Colorectal cancers arise due to the accumulation of different kinds of mutations in their DNA. The type of mutation that occurs most frequently within a tumor is determined by which DNA maintenance pathways are disrupted during tumor growth. This mutational pattern confers specific growth properties to the tumor cells and can change how the tumor is seen by the body’s immune system. Three of the key immune cell types for detecting tumors are dendritic cells, macrophages and T cells. We hypothesize that cancers with more mutations are better at activating all three of the cell types and that those cells types work together to coordinate immune detection and destruction of the cancer. The primary goal of the proposed studies is to uncover the underlying mechanisms that govern these interactions. Doing so will identify promising new therapeutic targets to boost immune detection in cancer patients with any mutation pattern. The benefit of this project to Canadian Blood Services is that cancer patients often require blood products during their treatment and decreasing the overall burden of cancer will ease demand on the Canadian blood supply and free up blood products for use in other needy patients.

Project ID: 2023.007 

Title: Isolation of RNA from Peripheral Blood Monocytes 

Project Approval Date: 2023-03-20 

City: Winnipeg 

Type of Organization: Government 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: Latent tuberculosis represents a health concern to the Canadian population as ~10% of those infected reactivate and have the potential to infect others.  Although tests exist for identifying LTBI-positive individuals, there is currently no way to predict which individuals are at risk of reactivating.  We hypothesize that an RNA signature in the host PBMCs may permit this differentiation.  This proposal is to identify the optimal protocol for RNA isolation from PBMCs for future work on latent tuberculosis. 

Project ID: 2023.010 

Title: Identification of mechanisms that reduce immune cell activity against cancer 

Project Approval Date: 2023-06-18 

City: Ottawa 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: In addition to fighting infections, our immune system is also very well equipped to eliminate cancer cells. However, immune cells can get tired when they try to kill tumor cells for a prolonged time; something we call, quite literally, “exhaustion”. When they are exhausted, immune cells lose their ability to effectively kill tumor cells or to interact with each other. Unfortunately, the molecular mechanisms that underlie the establishment of immune exhaustion are not clear, and it is therefore hard to therapeutically revert immune exhaustion. In this study, we developed an unbiased approach to discover new molecular targets that will help immune cells regain stamina, exit the exhausted state and start killing cancer cells again. Discoveries from this project will help to design more effective cancer immunotherapies that will allow our immune system to better fight cancer. 

Project ID: 2023.013 

Title: Medical Laboratory Science Diploma Program at BCIT 

Project Approval Date: 2023-05-31 

City: Burnaby 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: The Medical Laboratory Science Program at BCIT uses donated blood products from NetCAD to make simulated samples for students to test. These samples (red cells and plasma) are used in the Transfusion Science labs and provide students with authentic testing experience. The courses, MLSC 1320, 2320 & 3320 Transfusion Science, are heavily lab based and providing real blood simulates the clinical environment and contributes to robust experiential learning. The samples are used for a variety of tests such as, but not limited to: ABO/Rh, DAT, Antibody screens, Antibody panels (3-5%, 0.8% gel, and enzyme), eluates,and phenotyping. Without the samples provided by NetCAD, the program and courses could not operate and would rely heavily on theoretical knowledge rather than the application within the lab setting. This would significantly compromise the learning experience.The BCIT Medical Laboratory Science program enrolls 96 students per year and prides itself on being the largest national program graduating certified Medical Laboratory Technologists (CSMLS certication) and can only do with cooperative established partnerships with our clinical colleagues including NetCAD.

Project ID: 2023.014 

Title: Research in leukemia mechanisms to discover novel therapies 

Project Approval Date: 2023-05-31 

City: Toronto 

Type of Organization: Academic 

Use of Animals: Yes 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: Survival rates for pediatric acute lymphoblastic leukemia (ALL) patients have greatly improved due to central nervous system (CNS) prophylaxis and risk-adapted multi-agent chemotherapy. Prior to the introduction of  CNS-prophylaxis  ~80% of children relapsed in the CNS; however even with contemporary ALL treatment protocols, 30-40% of relapses involve the CNS. Improved survival rates of pediatric patients have come at the expense of treatment-associated endocrine disorders, secondary brain tumors and irreversible neurocognitive late effects. Our research address knowledge gaps that continue to impede improved outcomes in pediatric ALL: 1) the molecular mechanisms by which ALL cells invade the CNS.  2) Biological evidence of targeted therapies that may prevent and treat CNS leukemia.  3) Identification of biomarkers predictive of CNS leukemia.Our objectives are: 1) evidence to support clinical evaluation of targeted agents to prevent CNS relapse and, 2) discovery and characterization of biomarkers predictive of CNS involvement and relapse risk in pediatric ALL.Relevance of this study to Canadian Blood Services: Almost all patients with leukemia require one or more transfusions during their care. Thus the products and services provided by CBS directly benefit leukemia patients. Our study aims to improve leukemia treatments, benefiting these patients and in so doing will also benefit CBS by reducing need for transfusions. 

Project ID: 2023.019 

Title: Understanding immune cell behaviour and interactions with engineering tissues in the context of fibrosis, obesity, and cancer 

Project Approval Date: 2023-06-15 

City: Toronto 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: Immune cells such as macrophages are present in all tissues of the human body and remain the main regulator of tissue health.  However, multiple diseases like fibrosis, obesity and cancer, can corrupt tissue macrophages to influence overall tissue microenvironment, promote disease progression, and ultimately affect disease outcomes. Unfortunately, the current understanding of the molecular mechanisms that underlie macrophage behaviours in fibrosis, obesity, and cancer remains limited.  These mechanisms may be tissue and context dependent, affected also by macrophage origin and state.  In this project, we propose using 3D disease models to fill in the current knowledge gap and understand macrophage behaviours and the means by which they interact with other cell types in disease. Identifying such molecular mechanisms would provide the grounds for novel therapeutic approaches to target macrophages to modulate onset, progression, and resolution of fibrosis, obesity, and cancer. 

Project ID: 2023.024 

Title: The Molecular Profile of Cachexia in Patients with Cancer 

Project Approval Date: 2023-10-24 

City: Edmonton 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: People with cancer lose weight and muscle which is poorly prognostic for survival. We are conducting research to understand how this muscle loss happens.  Using a piece of muscle taken from people who are having surgery for cancer, we can take it to the lab for examination of its characteristics. For this study we are hoping to understand the ability of the stem cells to become muscle cells.  To do this we have developed primary culture models of muscle that can be applied to understanding the role of tumor derived factors and chemotherapy in the repair and function of muscle cells. Use of human plasma is required to make our experimental conditions as close to the in body conditions as possible. 

Project ID: 2023.025 

Title: Investigating human immune tolerance in humanized mouse model 

Project Approval Date: 2023-08-01 

City: Toronto 

Type of Organization: Academic 

Use of Animals: Yes 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: For the patients who need the organ or therapeutic cell transplantation, immune rejection following the transplantations means the host immune system recognize the transplant as non-self and start to attack the transplant. Immune rejection threatens patients’ life and in clinics, immunosuppressive drugs can help inhibit the immune system and increase the transplants survival rate. However, there are many long-term side effects, such as toxicity of immunosuppressive drugs, higher infection risk and graft verse host disease (GVHD).We aim to explore how to induce the local immune tolerance in recipient to donor’s organ/tissues/cells after organ transplantation for better organ survival and life quality without immune suppressive drugs. Considering the ability of human pluripotent stem cells to differentiate into different mature lineages, such as neurons, insulin-producing cells, cardiac muscle cells, etc. Our approach is to genetically modify human pluripotent stem cells and screen the candidate immunomodulatory genes that have potential functionalities to regulate the immune rejection to non-self organs/tissues/cells. By combining our engineered cell technologies, we envision the development of cell lines that can generate allo-accepted, off-the-shelf therapeutic cell products, as well as immune privileged artificial tissues to host cell transplants for treating or preventing disease.We hope that all findings can be used in the transplantation medicine. 

Project ID: 2023.026 

Title: Engineered Cellular Immunotherapies for Organ Transplantation 

Project Approval Date: 2023-07-21 

City: Toronto 

Type of Organization: Academic 

Use of Animals: Yes 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: Lung transplantation – where a person’s diseased lungs are replaced with healthy donor lungs– is the only life-prolonging treatment option for severe lung disease. Unfortunately, the recipient’s immune system recognizes the donor tissue as foreign and, despite powerful yet toxic anti-rejection drugs, causes rejection of the organ, leading to only a ~50% chance of surviving 6 years after transplant. Better approaches are needed. Regulatory T cells (Tregs) are a type of immune cell that can block the function of cells causing rejection. Our ultimate goal is to harness the power of Tregs to prevent lung transplant rejection by giving them directly to the organ before transplant. In this study, we will be isolating Tregs from blood of healthy donors, modifying them and expanding them in culture for testing as a potential treatment for donor lungs – in order to halt the rejection process before it starts. In addition, other cells in the organ, both before and after transplant, are potential therapeutic targets; we have identified key blood cells in lung transplant recipients. Cells obtained from donor blood will also be studied in comparison to these lung-resident cells.  This work will lay the foundation for the development of a lung-directed cellular therapy to promote long-term survival after lung transplantation. Increasing the longevity of transplanted organs will improve the lives of many Canadians who need a transplant.We will use the isolated and expanded cells in the following studies:-Testing their potential  them as a cell therapy for discarded human lungs-Studying their gene expression (RNA sequencing)-Gene modification of Tregs (CRISPR)-Testing them in special mice that won’t reject human cells 

Project ID: 2023.031 

Title: Studying how sugar molecules regulate the immune system 

Project Approval Date: 2023-10-13 

City: Vancouver 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: My group studies how cellular carbohydrates called glycans regulate the activity of our immune system. The long-term goal of this research is to discover new molecules that can be therapeutically targeted to enhance the immune response to cancer cells (immunotherapy). In order to achieve this goal, we need to be able to isolate primary human immune cells from healthy blood donors, manipulate their carbohydrate structures and study how this affects immune cell activation.

Project ID: 2023.033 

Title: Mechanisms of Lipid Metabolism and Lipophagy in Vascular Disease 

Project Approval Date: 2023-10-13 

City: Ottawa 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: Our research focuses on understanding how fat turnover is regulated by autophagy and combines new scientific methodologies to address major gaps in our knowledge and to provide fundamental insights on how lipophagy regulates fat breakdown and inflammation in plaques. Lipophagy is a recently discovered cellular process, but the molecular components of this pathway are unknown. Identifying the lipophagy machinery and defining the role of lipophagy in atherosclerosis is the first step toward designing new therapeutic tools to promote reverse cholesterol transport from the artery wall. For this, we purify low density lipoproteins (LDL) from human plasma and modify these to generate foam cells, mimicking the lipid-loaded cells that aberrantly accumulate in the vascular wall during atherosclerosis, the major underlying cause of heart disease. We are employing human LDL to generate these foam cells in a dish in order to study the mechanisms of cholesterol removal from these cells. Researchers and pharmaceutical companies have been trying to develop drugs to increase reverse cholesterol transport for decades. As such, lipophagy would represent an extremely promising therapeutic strategy to treat heart disease. Simultaneous targeting of fatty deposit breakdown and dampening plaque inflammation would represent an important breakthrough for the treatment of cardiovascular diseases. 

Project ID: 2023.037 

Title: Understanding why some anticoagulated plasma units clot 

Project Approval Date: 2023-10-13 

City: Hamilton 

Type of Organization: Academic 

Use of Animals: No 

Canadian Blood Services Mandate: Transfusion Medicine 

Summary: A natural chemical called an anticoagulant is added to whole blood donations so they do not clot. Unclotted blood can be processed into different products that can help different patients. These products are plasma, platelet concentrates, and red blood cell concentrates. Most plasma units manufactured by Canadian Blood Services are frozen, thawed, and transfused without incident. Some are returned, however, when hospital staff detect visible particles in the bag. These are typically clots containing fibrin. The clots should not form in anticoagulated plasma. We hypothesize that donor-specific factors contribute to the clot. To test this idea, we will add increasing amounts of different substances that could be present in some donor samples. The substances will be tissue factor (a clot promoter found in skin that should not end up in the bag, but which might), polyphosphate (released from activated platelets), and two activated coagulation factors not ordinarily present in significant amounts. Our results will provide new information about sporadic clots in plasma units that could lead to new ways to avoid these rare but substandard products. 

Project ID: 2023.038 

Title: RCMP Police Dog Services Human Remains Detection Training 

Project Approval Date: 2023-10-11 

City: Innisfail 

Type of Organization: Government 

Use of Animals: Yes 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: The RCMP Police Dog Service Training Centre is the National training centre for the RCMP and the agencies they serve.  The training centre currently has a Human Remains (Cadaver) Detection profile that utilizes service dogs to detect human remains in various states of decomposition throughout various terrains.  The RCMP currently trains police dog teams across the country trained in this profile that support police and public agencies with both criminal and missing person investigations.  To aid in the training we currently work with the provincial Corner’s Service in Nova Scotia to obtain true source material from donors and families who realize the value in having valuable tool available to police and search and rescue groups.At this time our program is looking for a source of expired or surplus blood to train the dogs to detect its’s presence in or on such items such as fabric, soils, carpet and tools to name a few. 

Project ID: 2023.039 

Title: Design of an innovative immunoassay for blood glucose & hCG test 

Project Approval Date: 2023-12-22 

City: Delta 

Type of Organization: Industry 

Use of Animals: No 

Canadian Blood Services Mandate: Does not benefit Canadian Blood Services 

Summary: The objective of this study is to create a novel immunoassay tailored for home use, enabling users to accurately detect levels of human glucose and hCG (human chorionic gonadotropin). This innovative design serves a dual purpose: first, it facilitates the monitoring of Gestational Diabetes Mellitus, and second, it aids in identifying abnormal pregnancies. By combining these two widely tested biomarkers for pregnancy, the burden on the healthcare system is alleviated, and the convenience for pregnant women is significantly enhanced. 

Project ID: 2023.043 

Title: New method for identifying cell types in whole blood 

Project Approval Date: 2024-02-02 

City: Markham 

Type of Organization: Industry 

Use of Animals: No 

Canadian Blood Services Mandate: Transplantation Medicine 

Summary: Standard BioTools Canada (formerly Fluidigm Canada) is advancing the development of a product that may be used to automate comprehensive single cell analysis of human samples, in particular whole blood, on the mass cytometry instrument. The product is being co-developed with an automated data analysis solution for the rapid study of cell populations in human whole blood samples. The current technology enables the identification of at least thirty cellular biomarkers in a single white blood cell. We are actively developing products that can simplify and advance the quality of these results. In our research program, we have increased the number of biological targets that our technology can detect and expanded the number of biomarkers detected on a single white blood cell. Identification of white blood cell types is necessary for understanding disease biology, early detection and treatment blood disorders and other diseases that may be monitored. To create these products, healthy donor research participant blood is used. The ability to identify, enumerate and characterize all types of immune cells in a very small volume of blood will help not only adult patients, but greatly support pediatric hematology patients, where standard blood volumes cannot be collected from infants and young children. 

Project ID: 2024.002

Title: Exploring the Safety and Efficacy of New Gene Therapies

City: Edmonton

Type of Organization: Academic

Use of Animals: No

Canadian Blood Services Mandate: Transfusion Medicine

Summary: We want to determine blood compatibility of in-house prepared nanoparticles that are investigated for gene-based therapy. The nanoparticles will bear nucleic acids such as short interfering RNA (siRNA), plasmid DNA (pDNA) and messenger RNA (mRNA). The compatibility of these nanoparticles with blood is important in determining their safety and therapeutic efficacy. We want to see if the nanoparticles will remain intact in pooled blood and if there will be interactions between the nucleic acid cargo and the cells in blood. We plan to inspect cytokine secretion from the blood cells as a measure of biocompatibility, and to explore if changes in gene expression occur as a result of exposure to the nanoparticles. We will inspect gene silencing and gene expression enabled by the designed nanoparticles. A stable nanoparticle carrier for gene-based therapeutic agents will be developed upon successful completion of this project. We hope to show that our nanoparticles will not aggregate, will display controlled interactions with the cells of the blood component, elicit minimal cytokine response and minimal changes in gene expression, and deliver their cargo effectively to the cells. We plan to fine tune nanoparticle formulations so that nanoparticles that display the desired response with blood cells.

Project ID: 2024.006

Title: Cold Storage as an Alternative to Irradiation of Red Cells

City: Edmonton

Type of Organization: Canadian Blood Services/Academic

Use of Animals: No

Canadian Blood Services Mandate: Transfusion Medicine

Summary: To prevent transfusion-related deaths that are a direct result of activation of the recipient’s immune system, Canadian Blood Services eliminates white blood cells (WBCs) from red blood cell (RBC) products using two industry-standard approaches: filtration followed by irradiation if clinically indicated. However, in addition to logistical challenges, irradiation has been shown to affect RBC quality thereby these irradiated products also possess a shorter shelf-life. Previous work by our group has demonstrated that extended cold storage may be nearly as effective as irradiation in reducing the number and viability of any WBCs that remain post-filtration.

The objective of this study is to compare stored RCCs to units irradiated either a day or a week prior to transfusion in the context of 1) the number and functionality of their residual WBCs and 2) the quality of their RBCs. This will allow us to further characterize WBCs and RBCs in irradiated and cold stored products. These results will inform blood product management by potentially eliminating the need for irradiation, particularly when access is limited.