The COVID-19 pandemic caused by the virus SARS-CoV-2 is the deadliest pandemic of the 21st century. Despite well-documented evidence that COVID-19 vaccines are safe and effective, the exact ways through which the contents of the vaccine are carried from the muscle where they are injected to the lymph nodes where a protective immune response is generated, is not fully understood. COVID-19 vaccines contain a genetic sequence from the virus called mRNA, contained in small lipid particles. We will use cutting-edge techniques to visualize the specific cells in muscle tissue that take up these mRNA-containing particles and their migratory pathway to lymph nodes, which is still unclear. Additionally, we will determine the genes they express at each stage, and identify the immune cells they interact with. Finally, we will assess new mRNA vaccine formulations to determine the most effective formulation that provides protection against SARS-CoV-2. We will start in animal models of disease and establish the necessary groundwork prior to clinical trials with human patients. This research will help us improve the effectiveness of current COVID-19 vaccines and inform development of all mRNA-based vaccines for the future.
Research Location: UBC Biomedical Research Centre
Role of TAK1 in resident fibro/adipogenic progenitors. A Key modulator of the inflammatory milieu and a therapeuthic target in chronic diseases
In our aging society, degenerative complications of chronic diseases are on the rise and account for a significant percentage of deaths. Among these, fibrosis is the most common, and yet no therapy capable of mitigating its effects is available. Investigating and understanding the signaling pathways that influence fibrogenic progenitor (FAP) fate will not only elucidate a key component of the regenerative process but may reveal pathways that could be targeted therapeutically to prevent inflammation, fibrosis, and enhance regeneration or maintain muscle homeostasis.
Here, we will focus on the ability of these progenitors to attract to damaged tissues specific inflammatory cells (eosinophils) that have been linked to fibrosis, with the goal of learning how to prevent their excessive accumulation and thus prevent this prevalent complication of muscular dystrophies and other chronic diseases.
Generating tissue capable of forming blood-progenitor cells at clinical scales
Chronic diseases consume 67% of direct healthcare costs in Canada. Regenerative medicine (RM) is a powerful strategy to address chronic diseases. The next generation of RM therapeutics targets development of living cells and tissues to treat specific indications. Availability of stable progenitor stem cell bio-banks that can be differentiated to desired phenotypes is a crucial pre-requisite. My overarching goal is to understand how complex tissues emerge from pluripotent stem cells and use that knowledge to develop protocols to generate blood progenitor-forming tissues at clinical scales.
My approach rests on three complementary thrusts.
First, I will develop a computational model connecting the genetic code of the cells to their microenvironment to understand how interactions between the two govern cell fate.
Second, I will make pluripotent organoids to validate key parameters influencing earliest stages of stem-cell based blood development.
Finally, promising findings regarding parameters governing emergence of blood forming tissue will be tested in vitro via assays developed by the host lab, yielding pre-clinical data suitable for further technology development.
My work will reveal fundamental rules that govern the emergence of blood-forming tissues and generate new strategies for RM application. My computational approach will yield a new drug design & optimisation paradigm. The proposal will, thus, add to and reinforce BC's position as a leader in Regenerative Medicine.