The general goal of our research is to understand genetic and molecular mechanisms underlying specification of cell fates. We are particularly interested in the process of neurogenesis mediated by small non-coding RNA molecules, microRNAs that control the activity of chromatin remodeling complexes during neural development. In addition, we recently discovered that two brain-enriched microRNAs, miR-9/9* and miR-124, are neurogenic molecules that could promote direct conversion (reprogramming) of human fibroblasts into neurons when ectopically expressed.
We currently aim to:
1) devise cell-fate reprogramming strategies to generate human neurons of specific subtypes by directly converting human skin fibroblasts. Our reprogramming paradigm is based on the neurogenic cellular state provided by miR-9/9* and miR-124, and transcription factors that guide the neuronal conversion towards specific subtypes.
2) develop tissue culture models of neurological diseases using patient-specific neurons to study cell autonomous properties associated with the disease state in induced human neurons. We are currently developing human cell culture models of neuronal aging and Huntington’s disease using patient-specific neurons generated by neuronal reprogramming.
3) identify molecular mechanisms underlying the neurogenic activity of miR-9/9* and miR-124. We use interdisciplinary approaches (molecular genetics, genomics and biochemistry) to delineate how these microRNAs promote neuronal fate. Specifically, we are interested in understanding changes in chromatin remodeling complex activities and changes in chromatin/epigenetic landscape mediated by miR-9/9* and miR-124.