Department of Pharmacology and Toxicology
Ion channel kinetics and structure; Molecular and Cellular Biology; Neurobiology; Neuropharmacology
Our research program focuses on brain development, studying the development of the oligodendroglial and astroglial cell lineages in the central nervous system in normal, mutant and transgenic mice. The primary focus in the laboratory is on ion channels that regulate specification, migration and differentiation of these glial cells.
The oligodendrocyte generates CNS myelin, which is essential for normal nervous system function. Thus, investigating the regulatory and signaling mechanisms that control its differentiation and the production of myelin is relevant to our understanding of brain development and of adult pathologies such as multiple sclerosis. We have recently discovered that voltage-gated Ca++ channels are necessary for normal myelination acting at multiple steps during oligodendrocyte progenitor cells (OPCs) development, however nothing is known about its role in demyelination or remyelination events. Our research aims to determine if voltage-gated Ca++ channels plays a functional role in myelin repair. Using transgenic mice and new imaging techniques we are testing the hypothesis that voltage-gated Ca++ entry promotes OPC survival and proliferation in the remyelinating adult brain. Therefore, this work is relevant to developing means to induce remyelination in myelin degenerative diseases and for myelin repair in damaged nervous tissue.
Astrocytes are the most abundant cell of the human brain. They perform many functions, including biochemical support of endothelial cells that form the blood brain barrier, provision of nutrients to the nervous tissue and a role in the repair and scarring process of the brain and spinal cord following traumatic injuries. Our lab has made the novel finding of voltage-gated Ca++ channels function in astrocyte Ca++ homeostasis, and this has implications for plasticity in astrocyte development and for Ca++ regulation in general. We are testing the hypothesis that voltage-gated Ca++ entry plays a key role in astrocyte function and glial-neuronal interactions. We have generated a conditional knockout mice for voltage-gated Ca++ channels in astrocytes, these conditional knockout mice will allow the functional analysis of voltage-gated Ca++ channels in astroglia of the postnatal and adult brain. Analyzing such mice using a combination of behavioral, electrophysiological, imaging, and immunohistochemical techniques will provide new insights in our understanding of astroglial contribution to brain function.
These projects have been supported for many years by grants from the NIH and the National Multiple Sclerosis Society.