Shashi K. Ramaiah, DVM, PhD, DACVP, DABT
Adjunct Associate Professor
Department of Pathobiology
College of Veterinary Medicine
Texas A&M University
College Station, TX 77843-4467The research theme in this laboratory is centered on "Liver Pathogenesis". The current research focus is on "Liver Inflammation". The participation of Polymorphonuclear neutrophils (PMN) in the inflammatory response provides a first line of defense against invading organisms and liver toxic chemicals. However, inflammation has been called "double edged sword" as PMN can cause damage to surrounding tissues and a prolonged inflammatory response can contribute to a variety of pathological conditions. Inflammation is a complex reaction to injurious agents such as microbes and damaged, usually necrotic cells that consists of vascular responses, migration and activation of leukocytes and systemic reactions. The unique feature of the inflammatory process is the reaction of blood vessels leading to the accumulation of fluid and leukocytes in extravascular tissue.
The liver owing to its anatomic location and dual blood supply provides the first line of defense against microbes and toxins crossing the intestinal barrier. Although Kupffer cells (resident macrophages) are highly phagocytic and are able to remove microorganisms, they are also responsible for orchestrating an inflammatory response leading to effective recruitment of inflammatory cells (mostly neutrophils, monocytes, and T and B lymphocytes) to the liver. Inflammatory mediators such as tumor necrosis factor alpha, interleukins (IL-1, and IL-6), chemokines and reactive oxygen species (ROS) are considered to be major culprits for inflammatory cell recruitement into liver. These inflammatory mediators will prime and activate neutrophils in the hepatic microvasculature (sinusoids and postsinusoidal venules) leading to events in a sequential fashion culminating in hepatocyte death mostly by oncotic necrosis.
Although these mechanisms have been well investigated in other neutrophil-mediated liver injury models such as with hepatic ischemia-reperfusion and obstructive cholestasis, the mechanisms behind inflammatory cell recruitment in alcoholic liver injury (ALI) during alcoholic steatohepatitis (ASH) and non alcoholic steatohepatitis (NASH) has not been thoroughly studied. Currently, the research in our laboratory is aimed at identifying precise mechanisms by which inflammatory cells infiltrate the liver during ASH and NASH which are important life-style related metabolic diseases involving the liver. Our laboratory was the first to identify the relationship between matricellular protein Osteopontin (OPN) induction and hepatic neutrophil infiltration during ALI. Similar induction of OPN has since been reported in human alcoholic hepatitis patients. Osteopontin, is a secreted phosphoprotein induced within hepatocytes, Kupffer cells and biliary epithelium. The role of OPN mediated regulation of neutrophil and lymphocyte integrins, mechanisms of hepatic OPN upregulation and the role of ethanol metabolism on OPN induction are few of the ongoing projects in the laboratory.
In addition to research, I am a veterinary pathologist with roles in teaching and professional service. As a clinical pathologist, I teach veterinary students, interns and residents in clinical pathologic-related topics, and also participate in professional diagnostic service for the Texas Veterinary Medical Center. I am dedicated to performing high-quality research and diagnostic service to benefit animal and human patients.
Last Updated: August, 25th 2007
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