Our goal is to create normal and disease-specific induced pluripotent stem cells (iPSC) to study mechanisms of neurogenesis and to model diseases of the human nervous system. As part of the NIMH Stem Cell Center together with RUCDR Infinite Biologics®, we have made iPSC from Ataxia-telangiectasia, Schizophrenia, nicotine addiction disorders, Alzheimer's Disease, and autism. These projects involve many collaborators, mostly at Rutgers and UMDNJ. Our own laboratory will be using iPSC to determine how to program stem cells directly into specific neuronal subtypes for use in modeling disease and in therapeutic transplant.
We also study the role of microRNAs in neurogenesis. The recently-described class of genes encoding microRNAs provides a new level of regulatory control over gene expression. MicroRNAs, short, non-coding RNAs found in the RISC complex, are believed to inhibit translation or to destabilize target mRNAs. Using deep-sequencing technologies we recently identified 146 new human microRNAs expressed early in stem cell development. We predict that these largely human- or primate-specific microRNAs will function to stabilize differentiation pathways during early embryonic development and that they may be exploited to help program stem cells towards a desired cell type for therapeutic transplant. In collaboration with colleagues at the Broad Institute, we were awarded an NIH Challenge Grant to study small RNAs as regulators of epigenetic marking of chromatin.