Udayan Apte, PhD
PhD, University of Louisiana at Monroe, 2003
Postdoctoral Fellowship, University of Pittsburgh, 2008
Pathogenesis of Hepatocellular Carcinoma (HCC), Regulation of Hepatocyte Proliferation during Liver Regeneration
Mechanisms of Liver Regeneration, Regeneration Associated Molecular Patterns (RMAPs), Pathogenesis of Hepatocellular Carcinoma (HCC), Hepatic Progenitor Cell Biology
Liver is known for its remarkable capacity to regenerate following partial hepatectomy (PH) or after drug-induced liver injury. Our lab is focused on understanding the mechanisms behind liver regeneration following acetaminophen-induced acute liver failure, a condition that affects over 25,000 people each year and has very limited treatment options. Other aspect of this project is to identify and validate biomarkers of Liver regeneration also called as Regeneration Associated Molecular Patterns (RMAPs), which will aid the clinicians to determine the status of innate liver regeneration in acute liver failure patients. Along with cell culture and animal models to study liver regeneration after acute liver failure, we have developed clinical collaborations, which allow us to confirm our findings in patient samples of acute liver failure.
The second project in the lab is focused at determining the mechanism of liver size regulation. 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. Termination of liver regeneration is studied using two models, postnatal liver growth and liver regeneration after PH. The underlying hypothesis behind this project 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.
We are studying role of three signaling pathways including HNF-4alpha-mediated signaling, Wnt/beta-catenin pathway and Hippo Kinase pathway in liver regeneration after acute liver failure and in the termination of regeneration.
Huck I, Gunewardena S, Espanol-Suner R, Willenbring H, Apte U. Hepatocyte Nuclear Factor 4 alpha (HNF4a) activation in essential for termination of liver regeneration. Hepatology (In Press) doi: 10.1002/hep.30405. [Epub ahead of print] 2018
Huck I, Beggs K and Apte U. Paradoxical Protective Effect of Perfluorooctanesulfonic Acid Against High Fat Diet Induced Hepatic Steatosis in Mice. Internat J of Toxicol 37:383-392 2018
Bird TG, Müller M, Boulter L, Vincent DF, Ridgway RA, Lopez-Guadamillas E, Lu WY, Jamieson T, Govaere O, Campbell AD, Ferreira-Gonzalez S, Cole AM, Hay T, Simpson KJ, Clark W, Hedley A, Clarke M, Gentaz P, Nixon C, Bryce S, Kiourtis C, Sprangers J, Nibbs RJB, Van Rooijen N, Bartholin L, McGreal SR, Apte U, Barry ST, Iredale JP, Clarke AR, Serrano M, Roskams TA, Sansom OJ, Forbes SJ. TGFβ inhibition restores a regenerative response in acute liver injury by suppressing paracrine senescence. Sci Transl Med. 10(454). pii: eaan1230. doi: 10.1126/scitranslmed.aan1230, 2018
Borude P, Bhushan B, Gunewardena S, Akakpo J, Jaeschke H, and Apte U. Pleiotropic Role of p53 in Injury and Liver Regeneration after Acetaminophen Overdose. AM J Pathol 188(6):1406-1418, 2018, PMID: 29654721
McGreal SR, Bhushan B, Walesky C, McGill MR, Lebofsky M, Kandel SE, Winefield RD, Jaeschke H, Zachara NE, Zhang Z, Tan EP, Slawson C, Apte U. Modulation of O-GlcNAc levels in the liver impacts acetaminophen-induced liver injury by affecting protein adduct formation and glutathione synthesis. Toxicol Sci. 162(2):599-610, 2018, PMID: 29325178
Bhushan B, Poudel S, Manley MW, Roy N, and Apte U. Inhibition of glycogen synthase kinase 3 (GSK3) accelerated liver regeneration after acetaminophen-induced hepatotoxicity in mice. Am J Pathol 187(3):543-552, 2017, PMID: 28068511, PMID: 28068511
Jiang L, Fang P, Weemhoff JL, Apte U, Pritchard MT. Evidence for a "Pathogenic Triumvirate" in Congenital Hepatic Fibrosis in Autosomal Recessive Polycystic Kidney Disease. Biomed Res Int. 2016:4918798, 2016, PMID: 27891514
Sun L, Beggs K, Borude P, Edwards G, Bhushan B, Walesky C, Roy N, Manley MW, Gunewardena S, O'Neil M, Li H, Apte U. Bile Acids Promote Diethylnitrosamine-induced Hepatocellular Carcinoma via Increased Inflammatory Signaling. Am J Physiol Gastrointest Liver Physiol. 311(1): G91-G104, 2016, PMID: 27151938