School of Biomedical Sciences cordially invites you to join the following seminar:

Speaker: Professor Paul Monga, Senior Vice Chancellor Chair in Organ Pathobiology and Therapeutics, Director of Organ Pathobiology and Therapeutics Institute, Director of Pittsburgh Liver Research Center, Associate Dean of Research of Pitt School of Medicine, Professor of Pharmacology and Medicine, University of Pittsburgh and University of Pittsburgh Medical Center
Talk Title: Targeting beta-catenin for personalized treatment of HCC

Date: 18 December 2024 (Wednesday)
Time: 4:00 pm – 5:00 pm
Venue: HKJC-S3, G/F, Room G-05, The HKJC Bldg for Interdisciplinary Research, 5 Sassoon Road
Host: Professor Stephanie Ma

Biography

Prof. Paul Monga completed his medical training and internship in India, and his post-doctoral training in Gastroenterology, Hepatology & Molecular Biology at Washington D.C., learning about liver development and signal transduction. He joined the University of Pittsburgh in the Department of Pathology in 1999 for his second postdoctoral fellowship where he trained in the areas of liver regeneration and liver tumors. In 2001 he became faculty head and was appointed on tenure stream in 2003. He currently is the Senior Vice Chancellor Endowed Chair in Organ Pathobiology, and Professor of Pharmacology and Medicine. He is also the inaugural director of the Organ Pathobiology and Therapeutics Institute (OPTIn) and is also the founding director of the Pittsburgh Liver Research Center (PLRC). whose members study liver injury, repair and transformation. For the last 25 years, Prof. Monga’s lab has been focused on elucidating the cellular and molecular underpinnings of hepatic pathophysiology especially of liver development, regeneration, transdifferentiation, and tumorigenesis focusing on innovations in regenerative therapies, cellular reprogramming and precision medicine-based cancer treatments.

Abstract

The Wnt-b-catenin pathway plays key role in liver pathobiology. It is critical in liver development, liver regeneration after partial hepatectomy as well toxicant-induced liver injury, as well as in regulating the process of metabolic zonation of the liver lobule. However, its aberrant activation is observed in a notable subset of hepatocellular cancers including in 25-35% which exhibit gain-of-function missense mutations in CTNNB1 and another 5-10% which show loss-of-function mutations in AXIN1/2 or APC. Various molecular subclasses of HCC have now been defined through WGS and WES. HCC with Wnt-b-catenin activation represent one of these subclasses in each classification and these tumors usually show unique phenotype of being immune cold, better prognosis and more differentiated HCCs. Our group has generated multiple animal models using sleeping beauty transposon/transposase and/or crispr/cas9 that represent such subclass of tumors. These models have lent us well to describe the molecular underpinnings of the unique features of this subgroup of HCCs. This has not only helped us understand unique role of b-catenin in tumor metabolism but also in tumor microenvironment. These studies have revealed unique vulnerabilities for these subsets of tumors which has led to novel therapeutic strategies all the way from preclinical to now clinical settings. Among intriguing findings are the ones that b-catenin mutated HCCs are unique zonated in their gene expression and that b-catenin modulation impacts such zonation specific changes to reprogram tumor cells and nodules. These models have also allowed us to test the ability to directly target b-catenin itself to treat this molecular subclass of HCC for personalized treatment. Indeed, our recent studies have shown siRNA-based treatment strategies that allow successful control of the disease in preclinical models as well as opportunities to synergize these treatments with the current standard of care for even improved responses. Several of these preclinical studies are now leading to planned clinical trials in HCC space.

ALL ARE WELCOME.