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.
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.