Michael Koval, PhD
Professor of Medicine
Department of Medicine
Office: Whitehead Bldg 205
Michael Koval, Ph.D. has a long standing interest and expertise in studying cell membranes, with a particular emphasis in understanding the molecular basis for formation and remodeling of intercellular junctions. Dr. Koval received his Ph.D. in Cell Biology from Johns Hopkins University and was a Postdoctoral Fellow at Washington University. From there he became a faculty member in the Department of Physiology at the University of Pennsylvania with a jloint appointment at the Institute for Environmental Medicine. About a decade ago he joined the Department of Medicine and Emory Alcohol and Lung Biology Center at Emory University. Dr. Koval also has a joint appointment in the Department of Cell Biology.
As a postdoctoral fellow, Dr. Koval became interested in the trafficking and assembly of gap junctions, which his lab continues to study. The Koval lab has identified several steps in the quality control pathways which regulate assembly of gap junction proteins (connexins) into intercellular channels. This includes defining connexins involved in intercellular communication between type I and type II alveolar epithelial cells and identifying the first chaperone protein with the capacity to regulate connexin oligomerization, a thioredoxin fold protein known as ERp29.
Another major research direction in the Koval lab is to understand how tight junctions regulate the pulmonary air/liquid barrier. Molecular and cell biological approaches are used to define roles for several tight junction proteins (claudins, occludin, ZO-1, ZO-2) in normal lung barrier function and in pathologic conditions such as acute respiratory distress syndrome (ARDS). The Koval lab was the first to characterize claudin expression by lung epithelial cells and to identify specific claudin extracellular loop motifs which regulate the ability of different lung claudins to heterotypically interact which enables them fine tune paracellular permeability.
A long term goal of research in the Koval lab is to identify control points which augment barrier function as a means to improve the outcome of patients with ARDS and other forms of lung injury.
ResearchKoval Lab - http://kovallab.org/
Smith T.D., Mohankumar A., Minogue P.J., Beyer E.C., Berthoud V.M., Koval M. Cytoplasmic amino acids within the membrane interface region influence connexin oligomerization. 2012. J Membr Biol. 245(5-6):221-230.
Mitchell L.A., Overgaard C.E., Ward C., Margulies S.S., Koval M. Differential effects of claudin-3 and claudin-4 on alveolar epithelial barrier function. 2011. Am J Physiol Lung Cell Mol Physiol., 301:L40-L49
Das, S., J. Das Sarma, J. D. Ritzenthaler, T. Smith, J. Maza, B. E. Kaplan, L. A. Cunningham, L. Suaud, R. C. Rubenstein, M. Koval. 2009. Regulation of connexin43 oligomerization and trafficking by ERp29, Mol. Biol. Cell, 20:2593-2604