Satdarshan P. Singh Monga, Associate Professor
M. D., Dayanand Medical College and Hospital, India, 1993
S421-BST, 200 Lothrop St.
Pittsburgh, PA 15261
Phone: (412) 648-9966
Email: smonga@pitt.edu
Dr. Monga's laboratory is focused on understanding the molecular mechanisms of liver growth and development in health and disease especially trying to address the molecular basis of liver development, growth, regeneration and cancer. Several signaling pathways have been identified to direct such events including the Wnt/ -catenin, HGF/Met, PDGFR and others.
Liver development in mice is initiated at around E8-8.5 stages of gestational development. Once foregut endoderm gains 'competence', hepatic signatures are initiated during the process of 'induction'. The primitive liver bud contains bipotential stem cells or progenitors, which undergo expansion and regulated differentiation into hepatocytes and biliary epithelial cells during the process of 'morphogenesis'. One of the major focuses of Monga laboratory is to identify the molecular basis of hepatic morphogenesis. More specifically how does the hepatic progenitor or the bipotential stem cell undergo self-renewal (symmetric division), lineage specification and differentiate further towards primitive bile duct cells or immature hepatocytes (asymmetric division) and then to fully differentiated cells. Using conditional null mice, embryonic liver cultures and other modalities, the lab is investigating the roles, regulation and interactions of various pathways, which will not only further our understanding of this fundamental process of biology, but might also provide insight into the molecular basis of disease that recapitulates development in adulthood-hepatocellular cancer (HCC).
HCC is the third leading cause of death due to cancers and remains a disease with poor treatment options. A significant focus in Dr. Monga's laboratory is towards targeting this pathway and others, which are normally upregulated during liver development at the time of peak proliferation and stem cell renewal, as a novel therapeutic measure.
In addition, various animal models have been generated in Dr. Monga's laboratory, which conditionally overexpress or show lack of expression of important genes such as -catenin and others, which are in the process of being studied for the role of canonical Wnt signaling in additional liver diseases such as alcoholic liver disease, nonalcoholic fatty liver disease, glucose metabolism and others.
Dr. Monga's research is funded by the NIH (NIDDK and NCI), American Cancer Society and private pharmaceutical companies. In addition, Dr. Monga has trained numerous fellows, graduate students and others. Short-term rotational opportunities for students are available. Dr. Monga's team has been very productive as is reflected by publications in many high impact journals. Dr. Monga is also member of the University of Pittsburgh Cancer Institute and part of their Molecular and Cellular Oncology Program. He is also a member of McGowan Institute of Regenerative Medicine (MIRM), where is directs the McGowan Trainee Career Advancement Program (MTCAP). He is also CATER faculty and directs graduate courses on 'Stem Cells' and 'CATER' seminar series.
Recent Publication
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, IN PRESS
Wickline E, Awuah PK, Behari J, Ross M, Stolz DB, Monga SP. Hepatocyte Gamma-Catenin Compensates for Conditionally deleted Beta-Catenin at Adherens Junctions. Journal of Hepatology. IN PRESS.
Wagh PK, Gray JK, Zinser GM, Vasiliauskas J, James L, Monga SP, Waltz SE. beta-Catenin is required for Ron receptor-induced mammary tumorigenesis. Oncogene. 2011 Mar 21.
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 -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 and hepatocarcinogenesis in mice overexpressing serine-45 mutant beta-catenin. Hepatology, 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 -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. -Catenin activation promotes liver regeneration after acetaminophen-induced liver injury. Am J Pathol. 2009 Sep;175(3):1056-65.
