Cell differentiation is accompanied by massive epigenetic alterations necessary to produce desired cell types. Epigenetic editing can be exploited to better understand the role of epigenetics in differentiation. There have been many attempts to generate different cell types in vitro for regenerative medicine purposes. We will employ epigenetic editing to improve the quality of produced cells for cell therapy. Our main model will be the in vitro differentiation of hepatocytes for replacement therapy of injured liver.
Tumorigenesis is driven by genetic mutations and by alteration of epigenetic programs. We will employ epigenetic editing to better understand the role of specific DNA methylation patterns in tumor development and aggressiveness. Our findings may serve as a foundation for new approaches to cancer therapy.
Changes in DNA methylation occurring with aging, can accurately predict life expectancy. Higher mortality rates have been observed among individuals with DNA methylation age exceeding their chronological age. We will use a mouse liver transplantation assay and implant old hepatocytes in young animals and vice versa. Using this approach, we will examine whether the DNA methylation clock can be reversed in fully differentiated cells. This will deepen our understanding of the mechanisms governing the DNA methylation clock rate and its impact on aging.