Welcome to the Hsieh Lab!
Stem cells in the adult mammalian brain maintain tissue homeostasis, represent an extraordinary example of brain plasticity, and may contribute to repair and regeneration after brain injury, such as epilepsy and stroke. Moreover, as putative cancer stem cells, neural stem cells are suspected to be the root of brain malignancies like glioblastoma multiforme. The persistence of neurogenesis in the postnatal hippocampus suggests that stem cells might contribute to learning and memory formation, in a multistep process that involves cell proliferation, cell cycle exit, a choice between survival and death, and cell fate decisions, including neurons versus glial. Many factors can modulate 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 largely 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, histone deacetylases (HDACs), and MEF2 in adult neural stem cells. We have also taken a chemical biology approach to identify novel small-molecules to study self-renewal and differentiation of glioma stem cells.