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 transcription factors such as REST and co-repressors BRG1/HDACs in adult neural stem cells. We are also perfoming CRISPR/Cas9 mediated gene editing of human iPSC-derived organoids to model neurological diseases-in-a-dish, such as epilepsy and depression.