Student Profile: Larissa DePamphilis

Research Summary
Late stage blindness and visual impairment (BVI) caused by photoreceptor degeneration affects over 400 million adults worldwide. The World Health Organization (WHO) projects the prevalence of BVI to more than double by the year 2050. There is no effective cure for photoreceptor degeneration as they lack the ability to self-repair. Cell replacement therapy offers a new promise for vision restoration. In this therapy, stem or progenitor cells are transplanted into the host retina via the subretinal space, where they must 1) migrate to areas of damage, 2) achieve proper positioning, and 3) form functional synaptic connections with healthy, native cells to restore vision. However, transplantation studies have illustrated mixed success as biological mechanisms underlying the neuronal processes are incompletely understood. A principal challenge is the limited knowledge of stem cell behaviors and migration mechanisms within adult tissues. Computational modeling is a powerful tool when used in combination with experimental studies to unveil new cellular mechanisms. Agent based modeling (ABM) is a type of computational modeling that describe individual cells as autonomous “agents” that are programs to follow a set of interactions “rules” which are defined by either established molecular mechanism or newly observed behaviors from in vivo data. I investigate agent based computational modeling to define key cellular processes mechanistically and quantitatively, such as migration and differentiation. Related computational models have previously been developed to describe cell migration in adult tissues including cancer invasion, wound healing, development, and bone regeneration. This approach has not been applied to the stem cell transplantation process in the retina and our work aims to develop an experimentally validated model to describe the key mechanisms of replacement cell migration and infiltration into a host photoreceptor network.