Satdarshan (Paul) Singh Monga, MD
Professor of Pathology
Endowed Chair in Experimental Pathology
Dr. Monga is Endowed Chair for Experimental Pathology, Vice Chair of Experimental Pathology, Professor of Pathology (Division of Experimental Pathology) Professor of Medicine (Division of Gastroenterology, Hepatology & Nutrition), Director of the Cellular Approaches to Tissue Engineering and Regeneration (CATER) Program
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
- Hirohisa Okabe, Evan Delgado, Jung Min Lee, Jing Yang, Hiroki Kinoshita, Hiromitsu Hayashi, Allan Tsung, Jaideep Behari, Toru Beppu, Hideo Baba, Monga SP. Monga. Role of leukocyte cell-derived chemotaxin 2 as a biomarker in hepatocellular carcinoma. PLOS ONE 2014 Jun 3;9(6):e98817.
- Junyan Tao, Diego F. Calvisi, Sarangarajan Ranganathan, Antonio Cigliano, Lili Zhou, Sucha Singh, Lijie Jiang, Biao Fan, Luigi Terracciano, Sorin Armeanu-Ebinger, Silvia Ribback, Frank Dombrowski, Matthias Evert, Xin Chen, Monga SP. Wnt/β-catenin and Yap pathways synergize to promote hepatoblastoma development in mice and men. Gastroenterology, 2014 May 14. pii: S0016-5085(14)00610-6. doi: 10.1053/
- Evan Delgado, Jing Yang, Juhoon So, Stephanie Leimgruber, Michael Kahn, Tohru Ishitani, Donghun Shin, Gabriela Mustata Wilson, Monga SP. Identification and characterization of a novel small molecule inhibitor of beta-catenin signaling. American Journal of Pathology, 2014 May 9. (In Press).
- Jing Yang, Laura E. Mowry, Kari Nichole Nejak-Bowen, Hirohisa Okabe, Cassandra R. Diegel, Richard A. Lang, Bart O. Williams, Monga SP. Beta-catenin signaling in murine liver zonation and regeneration: A Wnt-Wnt situation. Hepatology 2014 Feb 20.
- Fanti M, Singh S, Ledda-Columbano GM, Columbano M, Monga SP. Triiodothyronine induces hepatocyte proliferation by protein kinase A-dependent β-catenin activation in rodents. Hepatology 2013, Oct. 07.
- Lee JM, Yang J, Newell PN, Singh S, Parwani A, Friedman SL, Nejak-Bowen KN, Monga SP. Beta-catenin signaling in hepatocellular cancer. Implications in inflammation, fibrosis and proliferation. Cancer Letters, 2013, Sep. 23.
- Delgado E, Bahal R, Yang J, Lee JM, Ly DH, Monga SP. β-Catenin Knockdown in Liver Tumor Cells by a Cell Permeable Gamma Guanidine-based Peptide Nucleic Acid. Curr Cancer Drug Targets. 2013 Oct;13(8):867-78
- Criscimanna A, Duan D, Rhodes JA, Fendrich V, Wickline ED, Hartman DJ, Monga SP, Lotze M, Gittes GK, Fong GH, Esni F. PanIN-specific regulation of Wnt signaling by HIF2. Cancer Res. 2013 Aug 1;73(15):4781-90.
- Nakamura I, Fernandez-Barrena MG, Ortiz-Ruiz MC, Almada LL, Hu C, Elsawa SF, Mills LD, Romecin PA, Gulaid KH, Moser CD, Han JJ, Vrabel A, Hanse EA, Akogyeram NA, Albrecht JH, Monga SP, Sanderson SO, Prieto J, Roberts LR, Fernandez-Zapico ME. Activation of the Transcription Factor GLI1 by WNT Signaling Underlies the Role of SULFATASE 2 as a Regulator of Tissue Regeneration. J Biol Chem. 2013 Jul 19;288(29):21389-98.
- Wickline E, Du Y, Stolz DB, Kahn M, Monga SP. β-Catenin at adherens junctions: Mechanism and biological implications in hepatocellular cancer after -catenin knockdown. Neoplasia. 2013 Apr;15(4):421-34.
- Awuah P, Nejak-Bowen KN, Monga SP. Role and regulation of PDGFR in liver development and regeneration. Am J Pathol. 2013 May;182(5):1648-58
- Pullara F, Guerrero-Santoro J, Calero M, Zhang Q, Peng Y, Spahr H, Kornberg GL, Cusimano A, Stevenson HP, Santamaria H, Reynolds SL, Brown IS, Monga SP, Houten BV, Rapic-Otrin V, Calero G, Levine AS. A general path for large-scale solubilization of cellular proteins: From membrane receptors to multiprotein complexes. Protein Expr Purif. 2013 Feb;87(2):111-9.
- Nejak-Bowen KN, Kikuchi A, Monga SP. β-Catenin-NF- B interactions in murine hepatocytes: A complex to die for. Hepatology 2013 Feb;57(2):763-74.
- Awuah PK, Rhieu BH, Singh S, Misse A, Monga SP. β-Catenin Loss in Hepatocytes Promotes Hepatocellular Cancer after Diethylnitrosamine and Phenobarbital Administration to Mice. PLoS One. 2012;7(6):e39771.
- Lade A, Ranganathan S, Luo J, Monga SP. Calpain Induces N-terminal Truncation of β-Catenin in Normal Murine Liver Development: Diagnostic implications in hepatoblastomas. J Biol Chem. 2012 Jun 29;287(27):22789-98.
- 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. Hepatology. 2012 Jun;55(6):1863-75.
- 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. 2012 Mar;55(3):931-40.