Why do we need neural stem cells in the postnatal and adult brain? Are they an integral part of adaptive responses to new stimuli? Do they respond to and participate in disease processes? Or are they contributors to deadly brain tumors? We are interested in the regulation of postnatal neural stem cells and how they modify brain homeostasis in health and disease. Throughout embryonic and postnatal development, neural stem cells give rise to differentiated neurons, astrocytes, and oligodendrocytes which modulate function of the adult nervous system. While during embryogenesis these progenitor cells are relatively abundant and help to construct the overall CNS architecture, during postnatal and adult periods they become restricted to specialized regions in the brain and produce progeny that participate in the modification of neural circuitry and brain homeostasis. The work in my laboratory centers around the molecular pathways regulating these specialized stem cells. A better understanding of these processes may lead to future therapies for patients suffering from pre/postnatal brain injuries, and brain tumors.
To better understand how stem cells contribute to brain remodeling in health and disease, we focus on the subventricular zone (SVZ) of the lateral ventricles in the postnatal brain, an area (niche) that contains a self-renewing population of neural stem cells. We have developed inducible Cre-transgenic mouse lines, as well as other new tools that can efficiently delete target genes in specific populations of SVZ cells after birth. A major focus in the lab is to elucidate important pathways that regulate stem cell function within the niche architecture - we are particularly interested in how this niche is generated and maintained during the postnatal period, and in pathways controlling stem cell proliferation that can lead to tumor formation. We use a variety of techniques including genetic mouse models, live imaging assays, stem cell cultures, and array analyses to study these processes. We are conducting both in vivo and in vitro-based screens to identify new pathways that regulate SVZ neurogenesis.
