The Michael Smith Foundation for Health Research (MSFHR) announced its 2021 scholar and research training awards, with four Centre for Blood Research (CBR) scientists among its 54 MSFHR Research Trainee award recipients. From investigating hematopoietic stem cells to engineering platelets using mRNA, these CBR researchers will take the lead in advancing science, addressing health priorities, and improving the health of British Columbians.
Congratulations to Drs. Anna Herrmann (Kizhakkedathu Lab), Grace Cole (Karsan Lab), Julyanne Brassard, and Katherine Badior (Kastrup Lab) for their awards!
Multifunctional immunomodulating conjugates for targeting and treating glycocalyx dysfunction in inflammatory conditions
Principal investigator: Dr. Anna Herrmann
Supervisors: Dr. Jayachandran Kizhakkedathu
Dr. Anna Herrmann
Diseases that involve the heart or blood vessels, autoimmune diseases (e.g. diabetes, multiple sclerosis), or the rejection of transplanted organs affect about 1 in 3 Canadians and constitute a significant cost to the Canadian economy. In the perpetuation of these diseases glycocalyx shedding plays a key role. The glycocalyx (literally meaning “sugar coat”) is a sugar polymer-based structure that covers the surface of the cells, which are lining all organs and blood vessels. It lies at the interface between bloodstream and organ tissue and represents the protective front line against inflammatory and immune-mediated diseases. Thus, we aim to specifically target and treat glycocalyx dysfunction by rapidly rebuilding it through a new cell surface engineering approach, which should enable organs to maintain or reestablish their function. To do so, we will develop polymer conjugates which can selectively bind and retain on the endothelial cell surface. The conjugates will present sugar moieties which resemble the natural glycocalyx layer. We anticipate to realize a novel approach with significant therapeutic potential to improve treatment for diverse disease conditions where glycocalyx dysfunction is contributing to the pathology.
Role of SASH1 in generation of hematopoietic stem cells
Principal investigator: Dr. Grace Cole
Supervisors: Dr. Aly Karsan
Dr. Grace Cole
For many patients with a serious blood disorder or malignancy the primary treatment option is a stem cell transplant (SCT), which involves destroying the unhealthy blood cells of the patient and replacing them with healthy donor stem cells. Unfortunately, a large number of patients are unable to find a suitable donor, and die as a result. Thus, there is an urgent need to identify new sources of healthy blood stem cells for these patients. One promising solution is to harvest other types of cells from the patient and reprogram them to become blood stem cells, which can then be reintroduced later. Key to the success of this approach is placing the cells in an environment which mimics how the first blood cells are generated during embryonic development (called endothelial to hematopoietic transition [EHT]). To date little research has focused on the external cues needed for EHT, and this presents a bottleneck to producing stem cells for SCT. Therefore, our project will use models of EHT to identify external drivers of EHT, and the mechanisms by which they program cells to transition into blood cells. The knowledge from this project will help to create protocols to reproducibly reprogram patient-derived cells into blood cells for SCT.
The influence of podocalyxin expression on immune response to ovarian cancer and the efficacy of an antibody-drug conjugate in immunotherapy
Principal investigator: Dr. Julyanne Brassard
Supervisors: Dr. Kelly McNagny
Dr. Julyanne Brassard
Despite significant advances in the treatment of many cancers, ovarian cancer still claims hundreds of lives in Canada every year. A molecule called podocalyxin is “switched on” by a high percentage of tumors from various cancer types including ovarian cancer and its expression is associated with poor prognosis. Since the immune system has a key influence in the control of tumor growth, one of my objectives will be to study how podocalyxin influences the immune response against tumors. In addition, Dr. McNagny’s team recently developed an antibody, called PODO447, which recognizes an exquisitely tumor-specific form of podocalyxin. Accordingly, my second objective will be to explore the use of this antibody as a method to either attract immune cells to cancer cells and kill them or as a tool to deliver toxins and chemotherapeutic agents specifically to tumor cells while sparing normal tissue. Preliminary experiments in animal models already are suggesting the efficacy of the latter approach. In conclusion, the results obtained in this project will allow us to take one more step toward the objective of ultimately treating ovarian cancer patients with the podocalyxin targeting therapies.
Engineering Platelets using therapeutic mRNA
Principal investigator: Dr. Katherine Badior
Supervisors: Dr. Christian Kastrup
Co-supervisors: Eric Jan
Dr. Katherine Badior
Platelet cells are routinely transfused during treatment of a range of conditions, due to their specialized roles in hemostasis. Despite the significant potential to enhance the efficacy and applicability of platelet transfusions, no techniques have yet been developed to engineer modified platelets. mRNA therapeutics is a promising novel class of nanomedicine with broad clinical applicability, capable of enhancing the physiological function of target cells by modifying cellular protein expression. The therapeutic potential of mRNA editing is particularly relevant to transfusion science, where the mechanisms of delivery to patients are well established. By engineering platelets using gold standard mRNA transfection strategies, their therapeutic potential can be maximized for diverse applications. Engineered platelets will be created using cutting-edge mRNA lipid nanoparticles. Successful mRNA editing will create platelets with enhanced biochemistry and improved hemostatic function. Results generated from this project will address knowledge gaps in platelet translation mechanism, and guide forthcoming research on the next generation of blood products, improving current standards of care in blood transfusion.
As MSFHR’s flagship funding opportunities, the Scholar and Research Trainee Programs support BC’s next generation of health researchers in developing their leading-edge research programs and helps them attract additional funding, hire and train highly-qualified personnel, create knowledge to inform policy, and advance research for the benefit of British Columbians.
The MSFHR Scholar Program supports early-career health researchers who are building leading-edge health research programs, training the next generation of scientists and expanding their potential to make significant contributions to their field. The MSFHR Research Trainee Program supports health researchers in the training phase of their research career to enable career development and enrich BC’s health research talent.