Dr. Rippe devotes his days to illuminating the causes of these pathological liver changes and to exploring targets for potential new therapies that will someday impede or prevent liver disease. Rippe studies the mechanisms of fibrogenesis as well as hepatic stellate cell proliferation (see figure below). Because the behavior of hepatic stellate cells in the human body is similar to that of hepatic stellate cells cultured in a Petri dish, Rippe can do much of his work using in vitro preparations.
Much of Rippe's research is dedicated to gaining a better understanding of the molecular basis of hepatic stellate cell activation. His laboratory has identified nearly 30 genes that are turned on or off during activation of hepatic stellate cells. One of the genes turned on during hepatic stellate cell activation is that for intercellular adhesion molecule-1 (ICAM-1). ICAM-1, a protein residing on the surfaces of cells, is responsible for helping white blood cells migrate from the bloodstream to injured tissue. Rippe's laboratory was the first to show that hepatic stellate cells actively mediate the migration of white blood cells during the inflammatory response, a role that hepatic stellate cells almost certainly fulfill in the inflammation associated with liver disease. In related studies, Rippe and his colleagues found that the gene for a B-crystallin, a protein that appears to protect liver cells from the stressful effects of assault by excessive alcohol and other harmful stimuli, is also turned on following hepatic stellate cell activation.
While much of Rippe's work focuses on increased hepatic stellate cell protein production during ethanol-associated activation, he is also interested in identifying the cellular signals that cause the hepatic stellate cells themselves to proliferate.
Center Line Articles
Click here for a list of publications from PubMed
Hines IN, Rippe RA. Role of hedgehog signalling in bile ductular cells.Gut. 2008 Sep;57(9):1198-9.
Jung Y, Brown KD, Witek RP, Omenetti A, Yang L, Vandongen M, Milton RJ, Hines IN, Rippe RA, Spahr L, Rubbia-Brandt L, Diehl AM. Accumulation of hedgehog-responsive progenitors parallels alcoholic liver disease severity in mice and humans.Gastroenterology. 2008 May;134(5):1532-43.
Kremer M, Perry AW, Milton RJ, Rippe RA, Wheeler MD, Hines IN. Pivotal role of Smad3 in a mouse model of T cell-mediated hepatitis. Hepatology. 2008 Jan;47(1):113-26.
Ivester P, Roberts LJ 2nd, Young T, Stafforini D, Vivian J, Lees C, Young J, Daunais J, Friedman D, Rippe RA, Parsons CJ, Grant KA, Cunningham C. Ethanol self-administration and alterations in the livers of the cynomolgus monkey, Macaca fascicularis. Alcohol Clin Exp Res. 2007 Jan;31(1):144-55.
Isayama F, Hines IN, Kremer M, Milton RJ, Byrd CL, Perry AW, McKim SE, Parsons C, Rippe RA, Wheeler MD. LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in mice. Am J Physiol Gastrointest Liver Physiol. 2006 Jun;290(6):G1318-28.
Yavrom S, Chen L, Xiong S, Wang J, Rippe RA, Tsukamoto H. Peroxisome proliferator-activated receptor gamma suppresses proximal alpha1(I) collagen promoter via inhibition of p300-facilitated NF-I binding to DNA in hepatic stellate cells. J Biol Chem. 2005 Dec 9;280(49):40650-9.
Rippe RA, Stefanovic B. Methods for assessing the molecular mechanisms controlling gene regulation. Methods Mol Med. 2005;117:141-60.
Yang L, Bataller R, Dulyx J, Coffman TM, Gines P, Rippe RA, Brenner DA. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. J Hepatol. 2005 Aug;43(2):317-23.
Yang L, Magness ST, Bataller R, Rippe RA, Brenner DA. NF-kappaB activation in Kupffer cells after partial hepatectomy. Am J Physiol Gastrointest Liver Physiol. 2005 Sep;289(3):G530-8.
Yang L, Bataller R, Dulyx J, Coffman TM, Gines P, Rippe RA, Brenner DA. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. J Hepatol. 2005 Jun 15.