Stem cells have two fundamental properties: self-renewal and multipotency. During development, stem cells and resulting progenitor cells are responsible for generating all the tissues and cells of an organism. In adult, stem cells exist in many tissues throughout life and may play critical roles in physiological functions and tissue regeneration. The maintenance of their “stemness” state and commitment to differentiation are tightly controlled by intrinsic genetic and epigenetic program and extrinsic environment.
Neural stem cells in the postnatal brains could have significant roles in both normal brain functions, such as learning, memory and response to injuries. We are investigating how neural stem cells behave both under normal conditions and in response to brain injuries and the underlying molecular mechanisms. Our long-term goal is to establish a molecular basis for utilizing postnatal neurogenesis and neural stem cells in brain repair.
Epigenetic mechanisms, including DNA methylation, chromatin remodeling and the noncoding RNA-mediated process, have profound regulatory roles in mammalian gene expression. Disturbance in one or another of these interacting systems can lead to inappropriate expression or silencing of genes, causing an array of multi-system disorders.
Neurodevelopmental disorders are highly heterogeneous constellations of disorders, both in terms of etiology and clinical manifestations. We are investigating how epigenetic mechanisms regulate postnatal neurogenesis and neuronal maturation, and its implication in human neurodevelopmental disorders and mental disorders, such as Rett Syndrome, Autism, Fragile X syndrome, fetal alcohol spectrum disorder, and depression disorder (for an upcoming Keystone Symposia with this focus, click here).
Techniques used in our lab include isolation of neural stem cells from adult or developing mammalian brains; in vitro and in vivo analyses of neural stem cell self renewal, fate specification, cell migration, and neuronal maturation; isolation and analyses of primary neurons; recombinant lentivirus and onco-retrovirus-mediated gene delivery and gene knockdown; noncoding small RNA functional assays; Multi-color fluorescent in situ hybridization, fluorescent imaging and quantification; unbiased stereology; chromatin immuoprecipitation, DNA methylation analyses, laser capture microdissection, Genome-wide expression analysis, and real time quantitative PCR analysis.
Funding for our projects is provided by NIH, International Rett Syndrome Foundation (IRSF), Autism Speaks, American Heart Association, and University of New Mexico School of Medicine.
