Hematopoietic stem cells (HSCs) are the only cells within the bone marrow that possess the ability to both differentiate to all blood lineages, and to self-renew for life. These properties, along with the remarkable ability of HSCs to engraft conditioned recipients upon intravenous transplantation, have established the clinical paradigm for stem cell use in regenerative medicine. However, despite the enormous clinical potential of HSCs, surprisingly little is known about the mechanisms that regulate their fundamental properties of self-renewal and multi-potency. Our lab has a profound interest in understanding the mechanisms enabling self-renewal and multi-potency in HSCs, which we study using cellular, molecular, genetic and epigenetic approaches.
Our lab is also interested in understanding the extent to which the aging of the stem cell compartment contributes to the pathophysiological conditions arising in the aged hematopoietic system. To address this we are evaluating HSCs in the context of aging in order to elucidate the mechanistic basis for HSC decline. In particular we are exploring the contribution of epigenetic dysregulation to HSC aging. We are also studying the mechanisms through which stem cells maintain genomic integrity, and examining how age-dependent DNA damage accrual impacts stem cell functional capacity.
Numerous studies have shown that it is possible to experimentally reprogram the cellular identity of one cell type to another. One approach to effect cellular reprogramming involves enforcing expression of defined transcriptional regulators important for specifying one cell type in a different cell type in order to convert its fate. This methodology is perhaps best exemplified by the generation of induced pluripotent stem (iPS) cells from a variety of differentiated cell types by the ectopic expression of a small number of defined factors. This approach is also proving to be a viable method to reprogram a variety of cell types to alternative fates. Our lab is pursuing several lines of investigation aimed at reprogramming the cellular identity of a number of cell types into clinically useful cell types, including HSCs, by using various approaches including the use of powerful technologies developed in the lab.