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Research Expertise and Interest
Degenerative diseases, exemplified by Parkinson’s, Alzheimer’s, metabolic disorders, osteoporosis, and muscle atrophy, in which the bodies capacity to regenerate new tissue can no longer keep up with tissue death invariably accompany human aging. These disorders are debilitating for individuals and represent a major problem for society. One intriguing possibility is that stem cells residing in aged organs retain their intrinsic ability to regenerate but are not properly triggered in the aged environment and that rejuvenation of the aged niches is actually required for the organ repair by any stem cell: endogenous or transplanted, including the iPSC-derived. Specifically, productive responses of aged stem cells and repair of old tissues can be rescued, when young and old mice share blood circulation (Conboy et al., 2005) and by deliberate youthful calibration of Notch, TGF-beta or MAPK pathways (Conboy et al. Science, 2003; Conboy lab: Nature 2008, Aging Cell, 2009, Nature Communications, 2014, Stem cells, 2015, Oncotarget, 2015). These findings, as well as their recent extrapolation in our laboratory, strongly suggest that the development of effective stem cell based therapies for age-specific degenerative diseases critically requires much improved understanding of why endogenous stem cells in older tissue are not “working properly” even when they have the capacity to do so. The interconnected research venues pursued in my lab help to understand how the process of tissue repair is controlled, why the injured tissues are not productively repaired as we age; and to establish approaches that restore the regenerative potential both to the aged organ stem cells and transplanted cells exposed to the aged organ environments. Currently, we use the regeneration of skeletal muscle and hippocampal neurogenesis as our main experimental systems, but hope to identify fundamental mechanisms of aging within stem cell niches, that apply to broadly to all organs and tissues.