Effective functioning of the body’s tissues and organs depends upon innate regenerative processes that maintain proper cell numbers (homeostasis) and replace damaged cells after injury (repair). In many tissues, regenerative potential is determined by the presence and functionality of a dedicated population of stem and progenitor cells, which respond to exogenous cues to produce replacement cells when needed. Understanding how these unspecialized precursors are maintained and regulated is essential for understanding the fundamental biology of tissues. In addition, this knowledge has practical implications, as the regenerative potential of tissue-specific stem and progenitor cells can be exploited therapeutically by transplantation (to replenish the stem cell pool) or by endogenous manipulation (to boost the repair activity of cells already present in the tissue).
Work in my laboratory focuses on uncovering the intrinsic and extrinsic regulators of stem cell function, and revealing how changes in stem cell activity impact tissue regeneration throughout life. Our studies have identified novel regulators of stem cell trafficking, including the transcription factor EGR1, which uniquely co-ordinates the migration and proliferation of blood stem cells in order to maintain appropriate stem cell number in the bone marrow and to support peripheral immune and inflammatory responses. We also developed and applied marker-based cell sorting approaches to analyze precursor cells in skeletal muscle, and identified a subset of satellite cells (mononuclear cells found beneath the basal lamina surrounding mature muscle fibers) that act as muscle stem cells. We demonstrated that these unique stem cells exhibit robust self-renewal and myogenic differentiation activity, and can restore muscle function when transplanted into injured or diseased muscle.
We now are exploiting these systems to uncover the cellular and molecular processes that underlie the stem cell dysfunction that typically arises with advancing age and that can promote tumor development. Exciting new data from our studies suggests that stem cell aging is controlled at least in part by blood-borne mediators, which change with age and can be manipulated to reverse age-associated dysfunction. Our future work will use the new insights gained from these studies to enable novel interventions to delay or reverse the onset of age-related disease and extend the healthful life of aging individuals.
Fall 2012. SCRB 190. Understanding Aging: Degeneration, Regeneration, and the Scientific Search for the Fountain of Youth
with Lee Rubin
This lecture and discussion course will explore the fundamental molecular and cellular mechanisms that govern organismal aging and contemporary strategies to delay or reverse this process.