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.
Gunewardena S, Walesky C, Apte U. Global Gene Expression Changes in Liver Following Hepatocyte Nuclear Factor 4 alpha deletion in Adult Mice. Genom Data. 5:126-128, 2015.
Bhushan B, Walesky C, Manley M, Gallagher T, Borude P, Edwards G, Monga SPS, Apte U. Pro-regenerative Signaling After Acetaminophen-induced Acute Liver Injury in Mice Identified Using a Novel Incremental Dose Model. Am J Pathol. 184:3013-25
Saha SK, Parachoniak CA, Ghanta KS, Fitamant J, Ross K, Najem MS, Gurumurthy S, Akbay EA, Sia D, Cornella H, Miltiadous O, Walesky C, Deshpande A, Zhu AX, Hezel AF, Yen K, Straley K, Travins J, Popovici-Muller J, Gliser C, Ferrone CR, Apte U, Llovet JM, Wong KK, Ramaswamy S, Bardeesy N. Mutant IDH inhibits HNF4α to disrupt hepatocyte differentiation and promote cholangiocarcinoma. Nature 4;513 (7516):110-4, 2014
Manley S, Ni HM, Kong B, Apte U, Guo G, Ding WX. Suppression of Autophagic Flux by Bile Acids in Hepatocytes. Toxicol Sci. 137:478-90, 2014
Bhushan B, Borude P, Edwards G, Walesky C, Cleveland J, Li F, Ma X, Apte U. Role of Bile Acids in Liver Injury and Regeneration following Acetaminophen Overdose. Am J Pathol 183:1518-1526, 2013
Walesky C, Edwards G, Borude P, Gunewardena S, O'Neil M, Yoo B, and Apte U. Hepatocyte Nuclear Factor 4 alpha Deletion Promotes Diethylnitrosamine-induced Hepatocellular Carcinoma in Mice. Hepatology 57:2480-2490, 2013
Walesky C, Gunewardena S, Terwilliger EF, Edwards G, Borude P, Apte U. Hepatocyte-Specific Deletion of Hepatocyte Nuclear Factor 4 alpha in Adult Mice Results in Increased Hepatocyte Proliferation. Am J Physiol Gastrointest Liver Physiol. 304:G26-37, 2013, PMID: 23104559
Borude P, Edwards G, Walesky C, Li F, Ma X, Kong B, Guo GL, Apte U. Hepatocyte specific deletion of farnesoid X receptor delays, but does not inhibit liver regeneration after partial hepatectomy in mice. Hepatology. 56(6):2344-52, 2012, PMID: 22730081
Septer S, Edwards G, Gunewardena S, Wolfe AW, Li H, Daniel J, Apte U. Yes associated protein is involved in proliferation and differentiation in postnatal liver development. Am J Physiol Gastrointest Liver Physiol. 302:G493-G503, 2012, PMID: 22194415
Li H, Wolfe A, Septer S, Edwards G, Zhong X, Bashar Abdulkarim A, Ranganathan S, Apte U. Deregulation of Hippo kinase signaling in Human hepatic malignancies. Liver Int. 32:38-47, 2011, PMID: 22098159
Wolfe A, Thomas A, Edwards G, Jaseja R, Guo GL, Apte U. Increased Activation of Wnt/beta-catenin Pathway in Spontaneous Hepatocellular Carcinoma observed in Farnesoid X Receptor Knockout Mice. J Pharmacol Exp Ther. 338:12-21, 2011, PMID: 21430080
Udayan Apte, PhD
4087 HLSIC; MS-1018
3901 Rainbow Blvd.
Kansas City, Kansas 66160
F: (913) 588-7501