Stem cells in the adult mammalian brain are important for maintaining cellular homeostasis, and represent an exciting source of regenerative potential after brain injury, such as epilepsy and stroke. Moreover, as potential cancer stem cells, neural stem cells are suspected to be the root of brain malignancies like glioblastoma multiforme. The persistence of neurogenesis in the hippocampus suggests that stem cells might contribute to learning and memory formation, in a multi-step process that involves cell proliferation, cell cycle exit, a choice between survival and death, and cell fate decisions, including neuron versus glia. Many factors can regulate adult neurogenesis, such as seizure activity, stress, hormones, and aging, but how these cell-extrinsic signals transduce their fate-directing effects to the stem cell genome is completely unknown.
A major focus of our lab is to understand the signaling circuitry and transcriptional regulatory mechanisms that govern neural stem cell fate decisions in both normal and disease states. Current projects are aimed at defining the roles of transcriptional/epigenetic regulatory proteins such as NRSF/REST, NeuroD, and histone deacetylases (HDACs) in adult neural stem cells. We have also taken a chemical biology approach to identify novel small-molecules to study neural stem cell differentiation.
RESEARCH INTERESTS
Stem cell biology
Neurogenesis and regeneration
Chromatin remodeling
Epigenetic mechanisms
Epilepsy and seizure disorders
RECENT PUBLICATIONS
Hsieh, J., Nakashima K., Kuwabara T., Mejia E., and Gage F.H., "Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells" Proc Natl Acad Sci USA, 101:16659-16664, November 2004
Kuwabara T., Hsieh J., Nakashima K., Taira K., and Gage F.H., "A small modulatory dsRNA specifies the fate of adult neural stem cells" Cell, 116:779-793, March 2004
Hsieh, J. and Gage F.H., "Epigenetic control of neural stem cell fate" Current Opinion in Genetics and Development, 14:461-469, Spring 2004
SIGNIFICANT PUBLICATIONS
Jay W Schneider, Zhengliang Gao, Shijie Lie, Midhat Farooi, Tie-Shan Tang, Ilya Bezprozvanny, Doug E Frantz, Jenny Hsieh, "Small-molecule activation of neuronal cell fate" Nature Chemical Biology, 4:408-410, July 2008
Hesham Sadek, Britta Hannack et al., Eric Olson, Jenny Hsieh, Jay W Schneider, "Cardiogenic small molecules that enhance myocardial repair by stem cells" PNAS, 105:6063-6068, April 2008
Sebastian Jessberger, Kinichi Nakashima, Gregory Clemenson, Eunice Mejia, Emily Mathews, Kerstin Ure, Shiori Ogawa, Christopher M. Sinton, Fred H. Gage, Jenny Hsieh, "Epigenetic modulation of seizure-induced neurogenesis and cognitive decline" Journal of Neuroscience, 27:5967-75, 2007
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