Protein That Protects During Stress Sheds Light on How Diabetes Drug Prevents Tumors

Researchers at University of California San Diego School of Medicine have identified a previously unknown mechanism that helps fortify the structure and tight junctions between epithelial cells — a basic cell type that lines various body cavities and organs throughout the body, forming a protective barrier against toxins, pathogens and inflammatory triggers. Breaches of this barrier can provoke organ dysfunction and development of tumors.

The findings, published online in the current issue of eLife by senior author Pradipta Ghosh, MD … Read the Full Story from the UC San Diego Newsroom


Dr. Pradipta Ghosh

Pradipta Ghosh, MD

Pradipta Ghosh, MD, MBBS, is Professor of Medicine in the Division of Gastroenterology.

She is a graduate of the UC San Diego Internal Medicine Residency Training Program, the Gastroenterology Fellowship Training Program and the Department of Medicine Physician-Scientist Training Program.

A Triple Play for Gastroenterology at UC San Diego

Division of Gastroenterology physician-scientists John T. Chang, MD, Pradipta Ghosh, MD, and Bernd Schnabl, MD, all were inducted into the American Society for Clinical Investigation on April 15, 2016.

To become a member of the ASCI, one of North America’s oldest and most respected medical honor societies, outstanding young investigators must be nominated and their nominations reviewed, ranked and scored in a process that selects less than 80 scientists from all areas of medicine each year.

“To have three young investigators from a single institution receive this honor in a single year is remarkable,” said William Sandborn, MD, Professor of Medicine and Chief of the Division of Gastroenterology.

Said Sheila E. Crowe, MD, Director of Research in Gastroenterology, “This is indeed an exceptional achievement for John, Pradipta and Bernd as individuals, and they bring great honor to the Division collectively.”

The three honorees are Associate Professors of Medicine in the Division of Gastroenterology.

Chang-John_120x150

John T. Chang, MD

John T. Chang, MD, investigates fundamental mechanisms underlying lymphocyte fate specification in systemic and mucosal immune responses. This research theme has important relevance to human health and disease, particularly vaccine design for infectious diseases that affect the gastrointestinal tract and in developing new therapeutic approaches for inflammatory bowel disease.

Dr. Chang is principal investigator of several active research grants, including two NIH R01 grants, an NIH Director’s New Innovator Award, and a Crohn’s & Colitis Foundation of America Senior Research Award. These grants fund Dr. Chang’s research to elucidate mechanisms by which regulators of polarity and asymmetric division influence T lymphocyte fate specification and function during microbial infection; the process by which T lymphocytes develop into pathogenic cells that cause intestinal inflammation; and identifying new approaches that enhance the function of regulatory T cells for the treatment of inflammatory bowel disease.

He is also a past recipient of a Howard Hughes Medical Institute Physician-Scientist Early Career Award and a V Foundation V Scholar Award. The latter has supported his work on the role of the cellular degradation machinery in cancer stem cell homeostasis.

Dr. Chang earned his MD from Temple University. He took two years off during medical school as a Howard Hughes Medical Institute-National Institutes of Health Research Scholar to pursue research training. Dr. Chang completed his internship/residency and gastroenterology fellowship training, along with four years of postdoctoral research in immunology, at the University of Pennsylvania. He joined the UC San Diego Division of Gastroenterology faculty in 2009.

Dr. Pradipta Ghosh

Pradipta Ghosh, MD

Pradipta Ghosh, MD, investigates the cell biology of signal transduction to find new ways to understand and block the development and spread of cancer and other diseases. Dr. Ghosh’s work has established a new paradigm in signal transduction by characterizing a new family of proteins which allow diverse receptors to transactivate heterotrimeric G-proteins. She unraveled the molecular mechanisms that govern such activation and established its unique spatiotemporal features. Finally, she demonstrated the relevance of this paradigm to modern medicine by defining the therapeutic potential of key signaling interfaces in diverse pathophysiologic states including diabetes, organ fibrosis, and cancer.

Her research funding includes three NIH R01 research grants, among them two five-year National Cancer Institute research grants that support her projects, “Modulation of G Proteins by Growth Factors” and “Spatial Regulation of G Protein Signaling.”

Among her scholarly awards are an American Gastroenterology Association Research Scholar Award in 2008, a Burroughs Wellcome Fund Career Award for Medical Scientists in 2009, and a Doris Duke Charitable Foundation (DDCF) Clinical Scientist Development Award in 2010.

Dr. Ghosh joined the Division of Gastroenterology faculty as assistant professor of medicine in 2008. She is a graduate of the UC San Diego Internal Medicine Residency Training Program, the Gastroenterology Fellowship Training Program and the Department of Medicine Physician-Scientist Training Program. She earned her MBBS in medicine at Christian Medical College and Hospital, India.

Bernd Schnabl, MD, PhD

Bernd Schnabl, MD

Bernd Schnabl, MD, focuses his research on liver disease. In studies funded by an NIH R01 grant, a NIH U01 cooperative agreement, a VA Merit Award, and industry grants, he is examining the relationship between liver disease and the intestinal microbiota.

He seeks to understand mechanisms by which the intestinal microbiome, metagenome and metabolome promote the development of chronic liver diseases. The goals of his investigations include the identification of new therapeutic targets for patients with liver disease.

Dr. Schnabl’s past honors and awards include an NIH K08 Career Development Award from the NIH/National Institute of Diabetes and Digestive and Kidney Diseases and an American Gastroenterological Association/Astra Zeneca Faculty Transition Award. The K08 award supported his project, “Blocking Toll-Like Receptor 4 Signaling as Therapy in Hepatic Fibrosis.” He is currently Associate Editor of Digestive Disease and Sciences, the oldest continuously published gastroenterology journal in North America.

After he received his medical degree from the University of Freiburg in Germany, Dr. Schnabl spent three years in postdoctoral research at the University of North Carolina at Chapel Hill. He completed his medical residency at the University Hospital in Regensburg/Germany and his gastroenterology fellowship training at Columbia University College of Physicians and Surgeons in New York City.

He joined the UC San Diego Division of Gastroenterology in 2008.

The ASCI new member induction ceremony took place on Friday, April 15, at the 2016 Joint Meeting of the Association of American Physicians, the ASCI, and the American Physician-Scientists Association in Chicago.

Predictive Proteins: Elevated Levels Trigger Metastatic Progression of Cancer Cells

New biomarker may offer more precise and accurate prognoses of disease —

Researchers at University of California, San Diego School of Medicine and Moores Cancer Center, with colleagues in Spain and Germany, have unraveled how elevated levels of particular proteins in cancer cells trigger hyperactivity in other proteins, fueling the growth and spread of a variety of cancers. … Read the Full Story from the UC San Diego Newsroom


Dr. Pradipta GhoshDr. Pradipta Ghosh is senior author of the study report, which appears in the February 26 online publication of Scientific Reports.

Pradipta Ghosh, MD, is Associate Professor of Medicine in the Division of Gastroenterology.

Read Study Report (Full Text; Open Access)

Golgi Trafficking Controlled by G-Proteins

A family of proteins called G proteins are a recognized component of the communication system the human body uses to sense hormones and other chemicals in the bloodstream and to send messages to cells. In work that further illuminates how cells work, researchers at University of California, San Diego School of Medicine have discovered a new role for G proteins that may have relevance to halting solid tumor cancer metastasis.

The study is reported online April 9 in Developmental Cell.

“Our work provides the first direct evidence that G proteins are signaling on membranes inside cells, not just at the cell surface as has been widely believed for several decades,” said Pradipta Ghosh, MD, associate professor and senior author. “This is significant because the G-protein pathway is a target of at least 30 percent of all current drugs on the market.” … Read the full story from the UC San Diego Newsroom


Pradipta Ghosh, MDDr. Pradipta Ghosh, is associate professor of medicine in the Division of Gastroenterology.

Visit the Ghosh Laboratory website

See Full Text of Article in Developmental Cell (UC San Diego only)

Dr. Pradipta Ghosh Receives Clinical Research Mentorship Grant from Doris Duke Charitable Foundation

Dr. Pradipta Ghosh

Three years ago, Department of Medicine physician-scientist Dr. Pradipta Ghosh received a Doris Duke Charitable Foundation Clinical Scientist Development Award to support her in the transition from junior researcher to independent investigator.

The grant funded her research for three fruitful years as she moved from assistant to associate professor and landed a five-year R01 research grant from the National Cancer Institute.

Now, Ghosh has won DDCF funding again — this time a Clinical Research Mentorship Grant to support her in mentoring medical student Gary Ma in the project, “Molecular Rheostats in Type II Diabetes – Novel Therapeutic Targets for Insulin Resistance.”

The DDCF Clinical Research Mentorship program is a competitive grant program that supports the development of a mentoring relationship between a clinical scientist previously funded through the foundation and a medical student with an interest in becoming a future clinician investigator.

This DDCF program funded 10 mentor/mentee teams this year.

About Dr. Ghosh

Pradipta Ghosh, MD, MBBS, is associate professor of medicine in the Division of Gastroenterology. She is a graduate of the UC San Diego Internal Medicine Residency Training Program, the Gastroenterology Fellowship Training Program and the Department of Medicine Physician-Scientist Training Program.

In her laboratory, Ghosh investigates the cell biology of signal transduction to find new ways to understand and block the development and spread of cancer and other diseases. Her National Cancer Institute research grant supports the project, “Modulation of G Proteins by Growth Factors.”

Looking back at the development of her career, she cites two important mentors, Drs. Stuart Kornfeld and Marilyn Farquhar.

“Stuart Kornfeld and Marilyn Farquhar are spectacular examples of good mentors and what good mentoring involves,” she said. “Being accessible, empowering, ensuring the freedom to probe, to expand the horizon.”

Stuart Kornfeld, MD, is David C. and Betty Farrell Distinguished Professor of Medicine and Director of the Division of Hematology at Washington University in St. Louis, where he directs the Medical Scientist Training Program and co-directs the Physician-Scientist Training Program.

Marilyn Farquhar, PhD, is Distinguished Professor of Cellular and Molecular Medicine and Pathology at UC San Diego.

About Her Mentor/Mentee Research Project

Abstract of the Study, “Molecular Rheostats in Type II Diabetes – Novel Therapeutic Targets for Insulin Resistance.”

“The overall goal of the proposed research is to unravel the mechanisms by which [Gα-interacting, vesicle-associated protein] (GIV) maintains insulin sensitivity and how its phosphoinhibition generates Insulin resistance (IR). Insights gained will not only help determine whether GIV can serve as a therapeutic target and a marker for prognosticating response to therapy in patients with IR, but also help decipher, access, and manipulate the entire signaling network to restore physiologic insulin response.”

Dr. Pradipta Ghosh Receives Burroughs Wellcome Fund Career Award

Dr. Pradipta GhoshDepartment of Medicine physician-scientist Dr. Pradipta Ghosh is one of only five researchers in the United States to receive a Burroughs Wellcome Fund Career Award for Medical Scientists this year.The $700,000, 5-year award honors Dr. Ghosh for her innovative investigation of G protein activity in the development and spread of cancerous tumors.

It’s a research project that she developed during her training here at UC San Diego. The Burroughs Wellcome award will support her as she continues this work as an independent faculty investigator.

Pradipta Ghosh, M.D., is Assistant Professor of Medicine in the Division of Gastroenterology.

Dr. Ghosh joined the faculty of the Division of Gastroenterology after she completed her subspecialty training last fall.

Read the full story from the UC San Diego News Center

She is a graduate of the UC San Diego Internal Medicine Residency Training Program, the Gastroenterology Fellowship Training Program and the Department of Medicine Physician-Scientist Training Program.In her laboratory, Dr. Ghosh investigates the cell biology of signal transduction to find new ways to understand and block the development and spread of cancer and other diseases.

Dr Ghosh obtained her postdoctoral training in the laboratory of Marilyn G. Farquhar, Ph.D., Distinguished Professor in the Department of Cellular and Molecular Medicine and Professor in the Department of Pathology.

The Burroughs Wellcome Career Award for Medical Scientists was established in 2007 to support new physician-scientists as they complete their training and establish their careers as independent academic investigators.

Also honored with a Burroughs Wellcome Fund Career Award this year were UC San Diego’s Quyen T. Nguyen, M.D., Ph.D., Assistant Professor of Surgery in the Division of Otolaryngology, and previous UCSD Department of Medicine research resident Chester Drum, M.D., Ph.D., currently on faculty at Harvard University School of Medicine.