The Grant lab is focused on the area of diabetic microvascular complications and stem cell biology. The team has been advancing the field of hematopoietic progenitor biology and the role of progenitors in physiological and pathological vascular repair in the retina for the last 15 years. We showed that healthy self-renewing adult hematopoietic stem cells (HSCs) have functional hemangioblast activity, that is, they can clonally differentiate into all hematopoietic cell lineages as well as endothelial cells that can revascularize the adult retina. Ocular diseases including retinopathy of prematurity (ROP), the leading cause of blindness in the young; diabetic retinopathy (DR), the leading cause of blindness in working age adults; and age-related macular degeneration (AMD), the leading cause of blindness in the elderly are associated with damaged vascular networks within the retina. Therefore, the ability to repair vascular damage could have a profound impact on these vision threatening conditions.
The Grant lab is interested in understanding the pathways of differentiation of HSCs. To this end, we have pre-programmed adult stem cells utilizing cell type-specific genes to confer differentiation specificity and enhance cell-specific repair. In particular, we expressed a retinal pigment epithelial (RPE) cell-specific transgene in HSC and examined stem cell homing, differentiation and function following RPE injury. We conclude that overexpression of cell-specific genes such as RPE65 and MITF are sufficient to drive differentiation of HSCs, facilitate homing to injured tissue and target repair. This type of targeted gene expression to force selective differentiation of adult stem cells offers novel therapeutic possibilities for tissue repair throughout the body.
