Himanshu Sharma
B.S. Case Western University, 2011
8th Year MSTP
4th Year Medical Student
Advisor: Holly Colognato, PhD
Department: Pharmacological Sciences, Stony Brook University
Graduate Program: Molecular & Cellular Pharmacology
Title: The Role of Dystroglycan in Mediating the Form and Function of the Subventricular Zone
Abstract:
The generation and maintenance of the brain requires the production of vast numbers of neural cells during development and maturity respectively. The largest population of proliferating cells in adult human, rodent, and primate brains is found in a unique neural stem cell (NSC) niche– the Subventricular Zone (SVZ). The SVZ generates neurons and glial cells at precisely the right time and place to support the generation of the brain, respond to injury, and meet the continuous need for new neural cells. Modulation of the extracellular matrix (ECM) by knocking out components such as laminin alters the production and maturation of cells -such as oligodendrocytes – that arise from the SVZ. Whether this phenotype is related to changes in the SVZ itself remains to be determined. One of our lab’s goals is to test the hypothesis that the extracellular matrix (ECM) plays a major role in regulating the function of this niche.
Dystroglycan is a receptor found on cells in the SVZ that mediates their interactions with ECM proteins such as laminin. Our lab has characterized a major phenotype in neural-specific dystroglycan-knockout mice marked by significant disorganization and dysregulation of neural cells that make up and arise from the SVZ stem cell niche. My research focuses on characterizing dystroglycan signaling in NSCs as well the epithelial-like ependymal cells during postnatal brain development by probing its associated signaling cascades, interaction with other ECM signals, and putative role in cell division. Using conditional dystroglycan knockouts in mice along with expression constructs designed to manipulate specific localization and functional modules on dystroglycan, we are working on understanding how signaling through this pathway mediates the startling phenotype present in dystroglycan null mice.
Awards:
Discussion Leader, Gordon Research Seminar on Neural Development
GSO Distinguished Travel Award
Provost Graduate Student Lecture
PhRMA Foundation Predoctoral Award
Publications:
(MSTP-supported publications indicated with an *)
McClenahan FK*, Sharma H*, Shan X, Eyermann C, Colognato H. Dystroglycan Suppresses Notch to Regulate Stem Cell Niche Structure and Function in the Developing Postnatal Subventricular Zone. In Press, Dev Cell. *Equal Contributions
Sharma H, Lang B, Silver J. (2014) Effects of the glial scar and extracellular matrix molecules on axon regeneration. In Textbook of Neural Repair and Rehabilitation. Edited by Selzer M, Clarke S, Cohen L, Kwakkel G, and Miller, R.; Chapter 27
Sharma H, Alilain WJ, Sadhu A, Silver J. (2012). Treatments to restore respiratory function after spinal cord injury and their implications for regeneration, plasticity and adaptation. Exp Neurol. 235:18-25.
