Satdarshan (Paul) Singh Monga, MD
Professor of Pathology
Endowed Chair in Experimental Pathology
Dr. Monga is the Director of the Division of Experimental Pathology.
200 Lothrop Street
Pittsburgh PA 15261
Office Telephone: 412-648-9966
- MD - Dayanand Medical College & Hospital, Ludhiana, India, 1993
- Postdoctoral Fellowship - Georgetown University, 1997
- Postdoctoral Fellowship - Temple University, 1999
Research ExpertiseDr. Monga's laboratory is engaged in elucidating the cellular and molecular basis of liver development, regeneration, cancer and injury. Specifically his lab is responsible for elucidating the many roles of the Wnt/ β-catenin signaling in liver physiology and pathology in governing an array of biological events like stem cell lineage specification and hepatocyte and cholangiocyte proliferation, apoptosis and differentiation. He has done this through generation of a variety of mouse models and through sophisticated in vitro assays. His lab has identified the activation of Wnt/ β-catenin signaling to be critical for normal liver regeneration in rats, mice and patients.
These key observations are currently being exploited for translational applications such as assessing activation of this pathway as a biomarker for regeneration in end stage liver disease, or modulating the pathway to induce hepatocyte proliferation. His laboratory has demonstrated an indispensable role of β-catenin signaling during liver development. More recently, they have identified a cleaved species of β-catenin that is temporally present during hepatic development and may be guiding the process of hepatocyte maturation. He went on to also show a key role of this pathway in adult hepatic progenitor expansion. Thus, his group for the first time demonstrated key roles of β-catenin in hepatic bipotential progenitor or hepatoblast expansion, lineage specification of hepatoblasts in biliary specification and eventually in hepatocyte maturation.
How β-catenin can have such pleiotropic roles continues to be a subject of active investigation in his laboratory. Clearly, such studies will have widespread implications in stem cell biology, hepatic tissue engineering and regenerative medicine.
Dr. Monga's lab has actively pursed the mechanisms leading to liver cancer. His lab has characterized phenotype of hepatocellular cancers (HCC) carrying β-catenin gene mutations. They have also generated transgenic mice carrying such mutations will employ this model to test novel drugs targeting this pathway that are being identified through computational and structural biology approaches. More recent work from his lab has challenged the dogma of absolute oncogene or tumor suppressor genes. They demonstrated loss of β-catenin, a traditional oncogene, to make mice more susceptible to HCC. In fact, β-catenin was demonstrated to have a cytoprotective and anti-oxidant role and its deletion in hepatocytes followed by administration of a chemical carcinogen led to chronic injury, inflammation, fibrosis and regeneration, a scenario commonly observed in a significant subset of HCC patients.
Interactions of β-catenin with additional transcription factors other than TCF/LEF such as NF- B, HIF, FOXO, and others may be responsible for a wide array of targets that may in turn define a variety of biological responses that are mediated by this pathway. The implications of these various interactions especially in HCC may be that while a subset of HCC patients with "bad" β-catenin activation will truly be candidates for its inhibition, others with "good" activation of this pathway will need to be excluded and thus will form an important basis of "personalized medicine" for HCC treatment. There are other important signaling pathways such as tyrosine phosphatases, and PDGFR/PI3K signaling that are being pursued actively in his lab for their roles in the liver.
Selected PublicationsView Dr. Monga's publications on PubMed
Awuah P, Monga SP. Cell cycle-related Kinase links androgen receptor & β-catenin signaling in HCC: Why men are at a loss? (Hepatology Elsewhere) Hepatology. 2012 Mar;55(3):970-4.
Yan W, Chang Y, Liang X, Cardinal JS, Huang H, Thorne SH, Monga SP, Geller DA, Lotze MT, Tsung A. High mobility group box 1 activates caspase-1 and promotes hepatocellular carcinoma invasiveness and metastases. Hepatology. 2012 Jan 11
Liu S, Yeh TH, Singh VP, Shiva S, Krauland L, Li H, Zhang P, Kharbanda K, Ritov V, Monga SP, Scott DK, Eagon PK, Behari J. β-catenin is essential for ethanol metabolism and protection against alcohol-mediated liver steatosis in mice. Hepatology. 2011 Oct 26.
Thompson MD, Wickline ED, Bowen WB, Lu A, Singh S, Misse A, Monga SP. Spontaneous repopulation of -catenin null livers with -catenin-positive hepatocytes after chronic murine liver injury. Hepatology. 2011 Oct;54(4):1333-43
Wickline E, Awuah PK, Behari J, Ross M, Stolz DB, Monga SP. Hepatocyte Gamma-Catenin Compensates for Conditionally deleted Beta-Catenin at Adherens Junctions. J Hepatol. 2011 Dec;55(6):1256-62. Epub 2011 Apr 13.
Wagh PK, Gray JK, Zinser GM, Vasiliauskas J, James L, Monga SP, Waltz SE. β-catenin is required for Ron receptor-induced mammary tumorigenesis. Oncogene. 2011 Aug 25;30(34):3694-704.
Lade AG, Monga SP. Beta-catenin signaling in hepatic development and progenitors: Which way does the WNT blow? Dev Dyn. 2011 Mar;240(3):486-500.
Nejak-Bowen K, Monga SP. Beta-catenin signaling, liver regeneration and hepatocellular cancer: Sorting the good from the bad. Semin Cancer Biol. 2011 Feb;21(1):44-58. Epub 2010 Dec 21.
Monga SP. Role of Wnt/β-catenin signaling in liver metabolism and cancer. Int J Biochem Cell Biol. 2009 Sep 9.
Thompson MD, Dar MJ, Monga SP. Pegylated interferon-alpha targets Wnt signaling by inducing nuclear export of beta-catenin. J Hepatol. 2011 Mar;54(3):506-12. Epub 2010 Oct 29 (Epub ahead of print).
Yeh TH, Krauland L, Singh V, Zou B, Devaraj P, Stolz DB, Franks J, Monga SP, Sasatomi E, Behari J. Liver-specific beta-catenin knockout mice have bile canalicular abnormalities, bile secretory defect, and intrahepatic cholestasis. Hepatology. 2010 Oct;52(4):1410-9.
Thompson MD, Awuah P, Singh S, Monga SP. Disparate cellular basis of improved liver repair in beta-catenin overexpressing mice after long-term DDC exposure. American Journal of Pathology, 2010 Oct;177(4):1812-22.
Zhang X, Tan X, Zeng G, Misse A, Singh S, Kim Y, Klaunig J, Monga SP. Conditional β-catenin loss in mice promotes chemical hepatocarcinogenesis: role of oxidative stress and PDGFR /PIK3CA signaling. Hepatology, 2010 Sep;52(3):954-65.
Nejak-Bowen KN, Thompson MD, Singh S, Bowen WC, Dar MJ, Khillan J, Dai C, Monga SP. Accelerated liver regeneration & hepatocarcinogenesis in mice overexpressing serine-45 mutant β-catenin. Hepatology, 2010 May;51(5):1603-13.
Behari J, Yeh TH, Krauland L, Otruba W, Cieply B, Hauth B, Apte U, Wu T, Evans R, Monga SP. Liver specific β-catenin knockout mice exhibit defective bile acid and cholesterol homeostasis and increased susceptibility to diet-induced steatohepatitis. Am J Pathol. 2010 Feb;176(2):744-53. Epub 2009 Dec 17.
Prince JM, Vodovotz Y, Baun MJ, Monga SP, Billiar TR, Gerlach JC. The Nitric Oxide Donor S-nitrosoglutathione (GSNO) Reduces Apoptotic Primary Liver Cell Loss in a 3D Perfusion Bioreactor Culture Model Developed for Liver Support. Tissue Eng Part A. 2010 Mar;16(3):861-6.
Nejak-Bowen KN, Zeng G, Tan X, Cieply B, Monga SP. Beta-catenin regulates vitamin C biosynthesis and cell survival in murine liver. J Biol Chem. 2009 Aug 18.
Apte UA, Singh S, Zeng G, Cieply B, Virji M, Wu T and Monga SP. β-Catenin activation promotes liver regeneration after acetaminophen-induced liver injury. Am J Pathol. 2009 Sep;175(3):1056-65.
Dai C, Stolz DB, Kiss LP, Monga SP, Holzman LB, Liu Y. Wnt/β-Catenin Signaling Promotes Podocyte Dysfunction and Albuminuria. J Am Soc Nephrol. 2009 Sep;20(9):1997-2008.
Apte U, Gkretsi V, Bowen WC, Mars WM, Luo JH, Donthamsetty S, Orr A, Monga SP, Wu C, Michalopoulos GK. Enhanced LR following changes induced by hepatocyte-specific genetic ablation of ILK. Hepatology. 2009 Sep;50(3):844-51.
He W, Dai C, Li Y, Zeng G, Monga SP, Liu Y Wnt/beta-catenin signaling promotes renal interstitial fibrosis. J Am Soc Nephrol. 2009 Apr;20(4):765-76.
Cieply B, Zeng G, Singh T-P, Geller DA, Monga SP. Unique phenotype of hepatocellular cancers with exon-3 mutations in beta-catenin gene. Hepatology 2009 Mar;49(3):821-31