University of Vermont

The University of Vermont Cancer Center

Bio for Steven Lidofsky, M.D., Ph.D.
Steven Lidofsky, M.D., Ph.D.

Steven Lidofsky, M.D., Ph.D.

Professor of Medicine, Gastroenterology and Hepatology Medicine
Department of Medicine
Professor of Pharmacology


Contact Information
E-mail: steven.lidofsky@uvm.edu
Office Location:
111 Colchester Ave, Smith 251, Burlington, VT 05401

Research Interests

The Role of Ion Channels in Liver Cell Function

Dr. Lidofsky’s research concerns how hepatocytes respond to metabolic and osmotic stress, a process that is critical to protection against a variety of conditions that produce liver injury. The liver plays a critical role in the metabolic processing and elimination of a variety of potentially injurious foreign compounds. Liver cells undergo dynamic changes in volume in response to nutrient uptake and metabolism, and irreversible cell swelling is a precursor to liver necrosis. Thus, an understanding of cell volume regulation is highly relevant to an understanding of liver cytoprotection during toxic exposure. It is known that in response to swelling, restoration of cell volume is achieved through reorganization of the cytoskeleton and fluid and electrolyte efflux through plasma membrane potassium and chloride channels, but the responsible volume sensors and signaling pathways are not well understood. We have found evidence that implicates the tyrosine kinase Src as a key regulator of these processes. In response to swelling, Src activates: 1) Vav, which drives Rho family GTPase cytoskeletal regulatory proteins, and 2) phospholipase C gamma, which regulates volume-sensitive potassium and chloride channels. Our current goals are to define how Src is activated upon swelling, how Vav effectors mediate actin reorganization, and how effectors of phospholipase C gamma regulate volume-sensitive ion channels. We anticipate that signaling proteins that we find to be critical for liver cell volume regulation will influence cytoprotection in pathological states and thus provide new insights into host susceptibility factors during toxic liver injury

Manuscripts:

1. Barfod ET, Moore AL, and Lidofsky SD: Cloning and functional expression of a liver isoform of the small conductance Ca2+-activated K+ channel SK3. Am J Physiol Cell Physiol 280:C836-C842, 2001

2. Roe MW, Moore AL, and Lidofsky SD: Purinergic-independent calcium signaling mediates recovery from hepatocellular swelling: implications for volume regulation. J Biol Chem 276:30871-30877, 2001
3. Moore AL, Roe MW, Melnick RF, and Lidofsky SD: Calcium mobilization evoked by hepatocellular swelling is linked to activation of phospholipase C?. J Biol Chem 277:34030-34035, 2002

4. Barfod ET, Moore AL, Melnick RF, and Lidofsky SD: Src regulates distinct pathways for cell volume control through Vav and phospholipase C?. J Biol Chem 280:25548-25557, 2005 

5. Barfod ET, Moore AL, Roe MW, and Lidofsky SD: Ca2+-activated IK1 channels associate with lipid rafts upon cell swelling and mediate volume recovery. J Biol Chem 282:8984-8993, 2007 

Publications

Barfod ET, Moore AL, Roe MW, Lidofsky SD. 2007. Ca2+-activated IK1 channels associate with lipid rafts upon cell swelling and mediate volume recovery. J Biol Chem 282:8984-8993. Pub Med ID: 17264085

Lidofsky SD. 2008. Nonalcoholic fatty liver disease -- diagnosis, relation to metabolic syndrome and approach to treatment. Current Diabetes Reports 8:25-30. Pub Med ID: 18366995

Lidofsky SD. 2010. Jaundice. In Feldman M, Friedman LS, Brandt LJ. (eds.) Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 9th ed., pp. 323-335.

Barfod ET, Moore AL, Van de Graaf BG, Lidofsky SD. 2011. Myosin light chain kinase and Src control membrane dynamics in volume recovery from cell swelling. Mol Biol Cell 22:634-650. Pub Med ID: 21209319

Zubarik R, Gordon SR, Lidofsky SD, Anderson SR, Pipas JM, Badger G, Ganguly E, Vecchio J. 2011. Screening for pancreatic cancer in a high-risk population with serum CA 19-9 and targeted EUS: a feasibility study. Gastrointest Endosc. 74:87-95. Pub Med ID: 21704809