Research Interests
Termination of Liver Regeneration, Pathogenesis of Hepatocellular Carcinoma (HCC), Regulation of Cell Proliferation
Liver is known for its remarkable capacity to regenerate following partial hepatectomy (PH) or after drug-induced liver injury. Following PH, the remnant liver lobes undergo extensive proliferation and liver mass is restored precisely to its pre-hepatectomy mass within 7-10 days after PH. Whereas the mechanisms of initiation of liver regeneration have been extensively studied, the mechanisms of termination of liver regeneration are not completely known. The precise size regulation and control of hepatic growth observed in during liver regeneration is fascinating and provides insights into the central mechanisms involved in cell cycle control in the organism. Studying these mechanisms are of immense importance because they not only provide understanding of basic mechanisms that regulate cell growth but also provide an opportunity to study cell cycle control mechanisms that could be deregulated in liver cancers. The underlying hypothesis behind the research in my laboratory is that the mechanisms that terminate cell proliferation and regulate organ size following liver regeneration are dysfunction in HCC and play a role in pathogenesis of liver cancers.
Termination of liver regeneration is studied using two models, postnatal liver growth and liver regeneration after PH. We are studying role of various factors/pathways involved in the termination of regeneration including Extracellular Matrix (ECM) proteins, HNF-4alpha, Wnt/beta-catenin pathway and Hippo Kinase pathway. We also study the role of these pathways in pathogenesis of HCC using variety of human, rat and mouse hepatoma cell lines as well as chemical carcinogenesis and tumor xenograft models.
Apte U, Gkretsi V, Bowen WC, Mars WM, Luo JH, Donhamsetty S, Orr A, Monga SP, Wu WC and Michalopoulos GK. Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase. Hepatology (May 6-Epub ahead of print) 2009.
Apte U, Thompson M, Cui S, Liu B, Zeng G, Cieply B, Monga SP. Wnt/beta-catenin signaling mediates oval cell response in rodents. Hepatology 47:288-95, 2008.
Apte U, Zeng G, Thompson M, Muller P, Micsenyi A, Cieply B, Kaestner KH, Monga SP. Beta-Catenin is critical for early postnatal liver growth. Am J Physiol Gastrointest Liver Physiol 292:G1578-85, 2007.
Zeng G, Apte U, Cieply B, Singh S, Monga SP. siRNA-mediated beta-catenin knockdown in human hepatoma cells results in decreased growth and survival. Neoplasia.9:951-959, 2007.
Apte U M, Zeng G, Muller P, Tan X, Micsenyi A, Cipley B, Dai C, Liu Y, Kaestner KH, Monga SP. Activation of Wnt/beta-Catenin Pathway During Hepatocyte Growth Factor-Induced. Hepatology 44:992-1002, 2006.
Apte UM, Banerjee A, McRee R, Wellberg E, and Ramaiah SK. Role of osteopontin in hepatic neutrophil infiltration during alcoholic steatohepatitis. Toxicol Appl Pharmacol. 207:25-38, 2005.
Corton JC*, Apte U*, Anderson SP, Limaye P, Yoon L, Latendresse J, Dunn C, Everitt JI, Voss KA, Swanson C, Kimbrough C, Wong JS, Gill SS, Chandraratna RA, Kwak MK, Kensler TW, Stulnig TM, Steffensen KR, Gustafsson JA, and Mehendale HM. Mimetics of caloric restriction include agonists of lipid-activated nuclear receptor. J. Biol. Chem. 279:46204-12, 2004. (* Contributed equally to this work)
Apte UM, Limaye PB, Ramaiah SK, Vaidya VS, Bucci TJ, Warbritton A, and Mehendale HM. Upregulated promitogenic signaling via cytokines and growth factors: potential mechanism of robust liver tissue repair in caloric restricted rats upon toxic challenge. Toxicol. Sci. 69:448-459, 2002.
Contact Information
Udayan Apte, Ph.D.
Assistant Professor
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
MS 1018
3901 Rainbow Blvd.
Kansas City, Kansas 66160
Phone: 913-588-9247
Fax: 913- 588-7501
Email: uapte@kumc.edu
Updated 8/24/09
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The University of Kansas Medical Center