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Department of Pathology
University of Pittsburgh
School of Medicine
S-417 BST
200 Lothrop Street
Pittsburgh, PA 15261
(412) 648-9550


v-line

 Department of Pathology
 Division of Experiemental Pathology



HEPATIC PATHOPHYSIOLOGY LABORATORY

PRINCIPAL INVESTIGATOR:


Satdarshan (Paul) Singh Monga, M.D.

- Professor of Pathology
- Associate Professor of Medicine







Office:

S421-BST, 200 Lothrop Street
Pittsburgh, PA 15261
Email: smonga@pitt.edu
       or: bowserlv@upmc.edu
Tel: 412-648-9966
Fax: 412-648-1916

Assistant:

Shari L. Tipton
Tel: 412-624-3507
Email: tiptonsl@upmc.edu

Lab 1:

S427-BST, 200 Lothrop Street
Pittsburgh PA 15261
Tel: 412-648-8146

Lab 2:

S433-BST, 200 Lothrop Street
Pittsburgh PA 15261
Tel: 412-383-7820

Mission Statement: Discerning the molecular mechanisms of liver health and disease, one pathway at a time!

RESEARCH:

About the Principal Investigator:

Dr. MONGA obtained his Medical Degree from Dayanand Medical College & Hospital, Ludhiana, Punjab, India in 1993. He did his postdoctoral fellowship in the laboratory of Dr. Lopa Mishra at the Department of Veterans Affairs Medical Center, Washington, D.C. in the laboratory of Gastroenterology, Molecular Biology and Development from 1996-1999, which was affiliated with Georgetown University, Washington, D.C., and later with Fels Cancer Institute, Temple University Hospital, Philadelphia.

Dr. Monga moved to the department of Pathology as a Research Associate in with Dr. George Michalopoulos in 1999 and was promoted to Research Assistant Professor in 2001 and to an Assistant Professor of Pathology in the tenure stream in 2003. Dr. Monga was promoted to an Associate Professor in 2007 and was tenured in 2009. He also became the director of the division of Experimental Pathology in 2008.

Dr. Monga is also Associate Professor of Medicine in the division of Gastroenterology. He is also a member of the McGowan Institute of Regenerative Medicine (MIRM) and has played an active role in CATER program and in directing the McGowan Trainee Career Advancement Program (MTCAP). He is also a member of the Molecular and Cellular Biology Program at the University of Pittsburgh Cancer Institute (UPCI). Dr. Monga is also an active training faculty in Interdisciplinary Biomedical Graduate Program in the Cellular and Molecular Pathology program. Other than being on many committees, Dr. Monga is the course director for the graduate courses entitled 'Stem Cells' (3.0) and 'Research Seminars in Regenerative Medicine' (1.0).

Ongoing Research:

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/β-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 β-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.

Thus Monga lab is focused on understanding the molecular and cellular basis of normal liver characteristics such as development, regeneration, metabolism and growth as well as of liver pathologies such as neoplasms (HCC and hepatoblastoma), fibrosis, cirrhosis, alcoholic liver disease, non-alcoholic fatty liver disease and others. This incorporates studies on cell proliferation, adhesion, differentiation, invasion, apoptosis, metabolism and on stem cells in adult, fetal and embryonic livers.

Dr. Monga's research is and has been funded by the NIH (NIDDK, NCI, NHLBI), American Cancer Society and private pharmaceutical companies.

ONLINE RESOURCES:

Dr. Monga's CV
Dr. Monga's NIH BIOGRAPHICAL SKETCH
Dr. Monga's trainee's worksheet

MEMBERS:

More Photos - 1,  2,  3,  4,  5,  6

Assistant Professor:
Jaideep Behari, M.D., Ph.D. (K08, NIH-NIAAA)
Assistant Professor of Medicine (GI)

Fellows:
Gang Zeng, M.D., Ph.D.

Graduate Students:

Lab Manager:
Sucha Singh

Others:
Tzu-Hsuan Yeh (Staff for Dr. Behari)
Prince Awuah (Rotation student)
Sneha Vivekanandhan (Undergraduate trainee)

PUBLICATIONS:

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/ -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 -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 -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 -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.

Dai C, Stolz DB, Kiss LP, Monga SP, Holzman LB, Liu Y. Wnt/{beta}-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

Copyright 1995-2009, Department of Pathology
University of Pittsburgh School of Medicine