ERIC VERDIN, MD

		Role of HDAC in Human Stem Cells Pluripotentiality and Differentiation Stem cells are able to develop into most of the specialized cells and tissues of the body and therefore have the potential to replace diseased cells with healthy functioning ones. It is the hope of the scientific and medical communities that the use of stem cell based therapies to treat diseases such as Alzheimerís disease, diabetes, heart disease and other degenerative conditions will one day be routine. Because this research field is still in its infancy, a number of scientific challenges must be overcome before promise of stem cells can be harnessed. In particular, we need to increase our understanding of the growth conditions, cellular biology and genetic events involved in stem cell survival and differentiation are key.
While more than 100 distinct stem cell lines have been derived, less than 20 are available in sufficient quantities for research purposes and of these, only a very limited number have studied with respect to understanding how stem cells grow and develop into target cells. Clearly there is a great need to study more cell lines to allow comparative analysis of growth conditions, signaling and gene expression processes. These studies will help clarify how these cells can be grown to sufficient quantities to be used clinically and will also help determine at stage these cells have maximum therapeutic potential. We are interested in understanding in molecular details two key properties of stem cells. First, self renewal is defined as the ability of stem cells to divide indefinitely, in contrast to non-stem cells which are limited in their ability to divide. Second, pluripotentiality refers to the ability of stem cells to differentiate in all cell types that are present in an adult organism. There is growing evidence that these two properties of stem cells are controlled at the central level via the interplay of cellular factors that control the transfer of DNA into RNA. Several key transcription factors have been identified that are unique to stem cells. Our laboratory has specialized during the last 20 years in the study of a family of proteins called histone deacetylases that control the activity of many transcription factors. However, no data exist on the possible role of these proteins in the self renewal and pluripotentiality of stem cells. We propose a series of experiments that will explore the role of histone deacetylases in these critical properties of stem cells. This information will ultimately advance our efforts at generating stem cells with therapeutic potential for use in the clinic

 
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