Robert S McCuskey

Professor Emeritus of Cell Biology and Anatomy,Pediatrics, and Physiology

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Research Interests

Our laboratory is studying dynamic biological processes in intact living organs such as the liver, spleen, pancreas, kidney, etc., using a combination of high resolution, light microscopic and electronic imaging techniques. During the past 30 years, such high resolution in vivo microscopic studies have expanded knowledge of dynamic structure-function relationships during health and disease since the methods permit the rate, duration, magnitude and direction of dynamic events to be directly visualized, evaluated, quantified and recorded continuously in life at the light microscopic level. Much of this work has been, and continues to be, focused on the mechanisms that regulate blood flow through small blood vessels in vital organs, such as liver, and how these are affected by drugs and various diseases. Advances in molecular and cellular biology have stimulated our laboratory also to use some of the fluorescence and spectrophotometric methods developed for studying molecular events in cultured individual cells isolated from organs; these techniques are being applied to studies of cells in their native environment within intact organs using the laboratory's unique microscopic techniques. Such studies are imperative in order to understand: (a) how individual cells function and communicate with each other in the intact, living organism; (b) how these functions are modified by disease, toxic substances, or drugs, and (c) how therapy can be developed to combat cellular dysfunction resulting from disease. For example, the results from such studies have tremendous potential for improving knowledge of biological molecular transport processes, cellular responses to drugs and disease, the interaction of tumor cells with host cells of the immune systems interact with foreign and host cells, as well as determining the distribution, interaction and effectiveness of therapeutic substances and novel drug delivery systems, such as liposomes, that are targeted to specific sites in the body, etc.

Current research using the above methodologies is focused on studying Kupffer cells and sinusoidal endothelial cells which are cellular components of the exchange vessels (sinusoids) in the liver. Kupffer cells produce a variety of mediators which are thought to play a key role in regulating blood flow through hepatic sinusoids, participate in host defense mechanisms, and influence liver cellular function. The endothelial cells are an early cellular target for injury by toxic substances altering sinusoidal blood flow and oxygen delivery. We are particularly interested in, not only the mechanisms in health, but also how they are modified by alcohol consumption alone or in combination with other toxicants as well as with viral or bacterial infection. In addition, we are studying the effects of biologically active substances in breast milk on the development of the liver in suckling rats.

Selected Publications

Ito Y Sørensen KK Bethea NW Svistounov D McCuskey MK Smedsrød BH McCuskey RS. Aug 2007. Age-related changes in the hepatic microcirculation in mice. Exp Gerontol, 42:789-97

Hasegawa T Ito Y Wijeweera J Liu J Malle E Farhood A McCuskey RS Jaeschke H. May 2007. Reduced inflammatory response and increased microcirculatory disturbances during hepatic ischemia-reperfusion injury in steatotic livers of ob/ob mice. Am J Physiol Gastrointest Liver Physiol, 292:G1385-95

Ito Y Doelle SM Clark JA Halpern MD McCuskey RS Dvorak B. Feb 2007. Intestinal microcirculatory dysfunction during the development of experimental necrotizing enterocolitis. Pediatr Res, 61:180-4

Ito Y Lugea A Pandol SJ McCuskey RS. Jan 2007. Substance P mediates cerulein-induced pancreatic microcirculatory dysfunction in mice. Pancreas, 34:138-43