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.


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.

Drs. Joachim Ix, Davey Smith Elected to American Society for Clinical Investigation

Two Department of Medicine physician-scientists have been elected to the American Society for Clinical Investigation (ASCI) this year.

Dr. Joachim Ix

Dr. Joachim Ix

Joachim H. Ix, MD, MAS, FASN, a nephrologist and epidemiologist, is professor and chief of the Division of Nephrology-Hypertension. He holds a secondary appointment in the Division of Preventive Medicine, Department of Family and Preventive Medicine.

Dr. Davey Smith

Dr. Davey Smith

Translational research virologist Davey M. Smith, MD, MAS, professor of medicine in the Division of Infectious Diseases, directs the Center for AIDS Research Translational Virology Core and is medical director of the Early Intervention Program at the UC San Diego Antiviral Research Center.

ASCI membership is a distinction that recognizes the nation’s most outstanding physician-scientists.

Seema Sharma Aceves MD, PhD, Elected to American Society for Clinical Investigation

Dr. Seema S. AcevesUC San Diego pediatric allergy/immunology physician-scientist Seema Sharma Aceves, MD, PhD, has been elected to the American Society for Clinical Investigation (ASCI).

She was formally inducted into the Society in a ceremony at the ASCI annual meeting in Chicago on April 26.

“It is a true honor to be included in this distinguished group of translational research leaders,” Aceves said.

“Seema represents the best and the brightest among clinical investigators today,” said Gary S. Firestein, MD, who nominated her for the honor.

“Her remarkable progress understanding the causes of an unusual and very debilitating disease in children made a significant impact on their quality of life.”

Firestein is professor of medicine in the Division of Rheumatology, Allergy & Immunology, Dean of Translational Medicine, Associate Vice Chancellor of Translational Medicine and director of the Clinical and Translational Research Institute.

Aceves, a specialist in pediatric eosinophilic esophagitis (EoE), is associate professor of clinical medicine in the Division of Rheumatology, Allergy & Immunology and associate professor of pediatrics in the Division of Allergy-Immunology-Rheumatology.

In her research, she investigates the mechanisms of tissue remodeling in EoE, exploring the role of pro-inflammatory and pro-fibrotic molecules. Major support for her work comes from a National Institutes of Health R01 research grant and funding from the Department of Defense.  |  Read NIH grant abstract

Her clinical specialty is pediatric allergy (Rady Children’s Specialists of San Diego). She practices at Rady Children’s Hospital – San Diego, where she directs the Eosinophilic Gastrointestinal Disorders Clinic.

Aceves received all of her medical training at UC San Diego. After she earned her MD and PhD in the Medical Scientist Training Program, she completed her internship and residency in the Department of Pediatrics and her fellowship training in allergy and immunology in the Department of Medicine.

She is board certified in allergy/immunology and pediatric allergy/immunology.

She was named a Physician of Exceptional Excellence in the 2012-2013 “San Diego’s Top Doctors” survey from the San Diego County Medical Society and San Diego Magazine and listed as one of the nation’s top doctors on the 2012-2013 U.S.News & World Report “Top Doctors” List.

Dr. Seth Field Elected to the American Society for Clinical Investigation

Dr. Seth FieldSeth J. Field, MD, PhD, Associate Professor of Medicine in the Division of Endocrinology and Metabolism, has been elected to the American Society for Clinical Investigation (ASCI).

ASCI membership is a distinction that recognizes the nation’s most outstanding physician-scientists.

“Seth is a highly innovative biomedical researcher, a caring clinician, and a teacher who devotes himself to mentoring learners at all levels,” said Wolfgang Dillmann, MD, Professor and Interim Chair of the Department of Medicine, who supported Dr. Field’s nomination. “He embodies the ideals of the ASCI.”

“It has been a pleasure to watch Seth’s career take off and succeed at UCSD,” said Jerrold M. Olefsky, MD, who proposed Dr. Field’s nomination. “He’s an outstanding and incisive scientist who still manages to be an exceptional clinician and teacher.”

Dr. Olefsky is Associate Dean for Scientific Affairs and Distinguished Professor of Medicine in the Division of Endocrinology and Metabolism.

Dr. Field has earned international recognition and major extramural funding for his original research. His investigations focus on the metabolism and signaling pathways of phosphoinositides, a group of lipid signaling molecules implicated in the pathophysiology of a range of human diseases.  |  Visit his laboratory website

“His findings,” said Dr. Dillmann, “have catalyzed a major paradigm shift in our understanding of the export of proteins from the cell.”

In 2009, Dr. Field and coworkers discovered that the Golgi protein GOLPH3 binds to phosphatidylinositol-4-phosphate in the trans-Golgi membranes and connects the Golgi to F-actin via binding the unconventional myosin MYO18A. The resulting tensile force plays an important role in the secretory pathway by drawing vesicles and tubules from the Golgi. In the process, the Golgi apparatus acquires its characteristic stretched and flattened shape.

Dr. Field and colleagues reported the finding in the journal Cell in October 2009. The discovery, announced in a UC San Diego press release, earned worldwide attention.  |  Read the report in Cell (free full text)

Now, in one of many subsequent studies, Dr. Field is examining how GOLPH3 may function to cause cancer and whether there are potential therapeutic targets in the GOLPH3 pathway. GOLPH3 has been identified as a cancer gene commonly associated with human cancers, including breast cancer.

This work is supported by a 5-year, $3.8 million Era of Hope Scholar Award for Breast Cancer Research he received last year from the US Army Medical Research and Materiel Command.

Dr. Field collaborated with Judith A. Varner, PhD, and coworkers in the tumor inflammation studies reported in the June 14, 2011, issue of the journal Cancer Cell. They have identified a single point at which myeloid cells are triggered to enter cancer cells and promote tumor growth: the PI-3 kinase-gamma enzyme. The report, pinpointing what may be an important new therapeutic target for cancer treatments, was highlighted in a mini-review in the same journal.  |  Read the report in Cancer Cell (free full text)

Dr. Field has also collaborated with Dr. Ronald Evans and coworkers in the Gene Expression Laboratory at the Salk Institute for Biological Studies in defining a novel negative feedback pathway for insulin signaling. The results identify a new target area for the development of insulin-sensitizing drugs.

In 2008, Dr. Field was honored with an NIH Director’s New Innovator Award, a five-year, $ 2.3-million research grant. Recipients of the NIH Director’s New Innovator Award are selected for the exceptional creativity and potential impact of their research.

In an earlier honor that brought major funding, the Burroughs Wellcome Fund granted Dr. Field a Career Award in the Biomedical Sciences in 2004. The five-year, $500,000 career awards are given to support outstanding postdoctoral researchers in their transition from advanced training to academic faculty service. The funding supported Dr. Field’s project, “Comprehensive analysis of phosphoinositide function.”

An active teacher in the Department of Medicine’s education programs, Dr. Field is also a member of the teaching and research faculty of the UC San Diego Biomedical Sciences Graduate Program. In addition, he is an investigator in the Cancer Biology program at the UC San Diego Moores Cancer Center.

Dr. Field received his MD degree from Harvard Medical School and his PhD in Genetics in the laboratory of Michael E. Greenberg, PhD, at Harvard. After his internship and residency in internal medicine at the Hospital of the University of Pennsylvania, he completed his fellowship in endocrinology at the Massachusetts General Hospital.

He returned to Harvard for his postdoctoral research training in cell biology and systems biology in the laboratory of Lewis C. Cantley, PhD. In 2005, he joined the UC San Diego Department of Medicine faculty as an assistant professor in the Division of Endocrinology and Metabolism.

Dr. Field and the other honorees for 2011, including Dr. Maike Sander from UC San Diego’s Department of Pediatrics, were introduced April 16 at the annual joint meeting of the ASCI and the Association of American Physicians in Chicago.

With the addition of Dr. Field, the ASCI now includes 63 current members of the faculty of the Department of Medicine.

Dr. Lucila Ohno-Machado Elected to the American Society for Clinical Investigation

Dr. Lucila Ohno-Machado

Dr. Lucila Ohno-Machado

Dr. Lucila Ohno-Machado, Professor of Medicine and founding chief of the Division of Biomedical Informatics, has been elected to the American Society for Clinical Investigation (ASCI).

Membership in the ASCI is a distinction that recognizes the nation’s most outstanding physician-scientists.

The honorees for 2010 were introduced April 24 at a joint meeting of the ASCI and the Association of American Physicians in Chicago.

Lucila Ohno-Machado, M.D., Ph.D., is a groundbreaking researcher and a respected director of advanced training programs in biomedical informatics. She joined the Department of Medicine faculty from Harvard Medical School in 2009.

“Lucila has always been a leader, and she will continue to lead UCSD in new directions in biomedical informatics, developing critical new tools that will help both basic researchers and clinicians in moving their programs forward,” said Kenneth Kaushansky, M.D., M.A.C.P., Helen M. Ranney Distinguished Professor and Chair of the Department of Medicine.

“Her election to ASCI highlights both her accomplishments and the increasing recognition of her field as a critical component of the academic medical center,” he said.

Dr. Ohno-Machado’s primary research interest is prognostic modeling, the development of statistical models to predict clinical outcomes. She is principal investigator of an NIH-funded grant to develop methods for improving the calibration of prognostic models and of another research project funded by the Komen Foundation to validate breast cancer biomarkers using computational techniques.

Dr. Ohno-Machado received her M.D. degree from the University of São Paulo and her Ph.D. in Medical Information Sciences and Computer Science from Stanford University.

She is an elected fellow of the American College of Medical Informatics and the American Institute for Medical and Biological Engineering. She serves as associate editor for both the Journal of the American Medical Informatics Association and the Journal of Biomedical Informatics.

Since 2004, during her tenure at the Brigham and Women’s Hospital of Harvard Medical School, Dr. Ohno-Machado has directed the Biomedical Research Informatics for Global Health Training (BRIGHT) Program, an educational consortium funded by the Fogarty International Center of the NIH.

The aim of the program is to unite U.S. researchers and institutions in a collaborative effort to conduct research and to develop informatics research training programs in low- and middle-income countries.

In its first five years, the program concentrated its efforts in Brazil, where it developed a certificate program in clinical informatics and supported a new doctoral program in bioinformatics at the University of São Paulo.

With a new 5-year, $1.23-million grant awarded last fall, the BRIGHT program is expanding its efforts to include Maputo, Mozambique, as well as additional areas of Brazil.

The Path to the Profession: John M. Carethers, M.D.

Dr. John M. Carethers, recently elected to the American Society for Clinical Investigation, in discussion with a medical studentThis year, Dr. John M. Carethers, Professor of Medicine and Chief of the Division of Gastroenterology, was honored with election to the American Society of Clinical Investigation (ASCI).

ASCI membership is granted to a select number of physician-scientists who have made extraordinary contributions in patient care and research before the age of 45.“John epitomizes the ideals of the ASCI – academic scholarship, teaching and clinical medicine,” says Ken Kaushansky, M.D., Helen M. Ranney Professor and Chair of the Department of Medicine.

“He is one of the true triple threats at UCSD, and all should aspire to achieve John’s high standards and accomplishments.”Dr. Carethers is a groundbreaking cancer researcher and a highly respected educator who has won teaching awards from housestaff, fellows, and the Vice Chancellor. He is the youngest division chief in the Department of Medicine.

Since he became chief in 2004, Dr. Carethers has expanded the faculty and secured several major grants, including the division’s first NIH Center grant for a Digestive Diseases Research Development Center.

In a recent interview, he looked back to his earliest steps on the path to this fruitful career, and to the upbringing that set him in this direction.

“My parents believed in education”

John M. Carethers was raised in Detroit, third youngest of 12 children.

“My parents believed in education, and they sacrificed a lot to get us educated,” he says. “They took care of us down to their last penny.”

His father, the only African-American student in his college, graduated in 1948 with a degree in mechanical engineering. At the time, companies in Detroit did not hire African-American engineers. He took a job with the Detroit Water and Sewage Department and worked his way up through the ranks.

On a modest income, John’s parents devoted themselves to providing the structure and the opportunities that best suited each of the children, one of whom was disabled.

“We were all different,” he says. “Different personalities, different strengths.”

All of John’s siblings attended parochial school and adhered to a schedule during their hours at home. Television was reserved for weekends. There were dedicated time periods for homework and for play.

As a child, he knew he wanted to be a doctor.

It Started with an Encyclopedia

Asked when he first became interested in medicine, Dr. Carethers says promptly, “Age 7.”

This was when his parents purchased the Encyclopaedia Britannica. The new books came with a requirement for summer projects: each child must make a weekly presentation on a topic of his or her choice at the Sunday afternoon meal.

Finding himself with the “A” volume, John discovered the section that depicted the human body. He remembers the wonder he experienced as he studied the colored overlays that superimposed muscles over organs over bones.

“Anatomy,” he says, smiling broadly. “Physiology. That was it. I knew I wanted to be a doctor.”

On summer Sundays, at the family table, the children gave their presentations. One of his brothers discussed flags; a sister talked about other cultures. John Carethers, age 7, presented the organ systems of the body.

He went to parochial school until high school, when he transferred to a magnet public high school in Detroit. There, he took college preparatory courses in physics, biology, and organic and inorganic chemistry.

In his college job as a unit clerk at Detroit Children’s Hospital, he had
his first chance to see medicine from the inside.

He covered several paper routes and he tirelessly cultivated a neighborhood clientele for his lawn mowing and snow shoveling services. When he started college, he had saved three thousand dollars.

For the first two years of college, per the family rule, he took public transportation and worked his way through his college courses. Then he purchased a car – for cash.

Although he was certain he wanted to become a doctor, he couldn’t imagine himself as a physician in practice. He had never seen what that life, and the path to it, was like.

First glimpse of medical practice

Then he took a job as a unit clerk at Children’s Hospital in Detroit during college.

“For three and a half years,” he says, “I published the OR schedule, made sure the operating doctors had privileges, and recorded the post-anesthesia charts in the computer. I met pediatric surgeons and I got to watch surgeries.”

It was his first inside look at medical practice, and it equipped him to envision his own future.

Although he considered becoming a pediatric surgeon,
“the real diagnosticians are the internists.
That was what interested me.”

Initially, he thought he would become a pediatric surgeon himself. When it came time for his third-year surgery rotation in medical school, however, one of his younger brothers came home with chicken pox and infected the others.

That and a postviral syndrome kept Dr. Carethers from immersing in his surgery rotation as he might have done. He did well in it, but by the time the rotation ended, his interest had expanded to other areas of medical practice.

“I thought about it,” he said, “and I felt the real diagnosticians are the internists. That was what interested me.”

During his residency in internal medicine at Massachusetts General Hospital, he determined that he would specialize in gastroenterology. He completed his fellowship training in gastroenterology at the University of Michigan Hospitals and joined the UC San Diego faculty in 1995.

Contributions in cancer research and policy

In the last 10 years, Dr. Carethers and his collaborators have made major discoveries in colon cancer. One of their most significant findings is that patients whose tumors have lost the capacity for DNA mismatch repair are resistant to chemotherapy with 5-fluorouracil, a common anticancer drug. Three other independent research groups have confirmed these findings.

Dr. Carethers and his coworkers demonstrated that this defect is present in 20% of people who have sporadic colon cancer, and in all families who have the hereditary colon cancer that is known as Lynch syndrome.

As a member of an NIDDK commission,
he helps to set national funding priorities for gastroenterology research.

Dr. Carethers is one of 16 appointed members of the National Commission on Digestive Diseases, which was proposed by the American Gastroenterological Association (AGA) and formed by the Director of the National Institutes of Health (NIH) in 2005. The mission of the NCDD is to assess the state of GI research and map out a 10-year plan to accomplish the most promising and pressing research goals.

The Commission advises the NIH Director and Congress, and thus exerts a direct influence on the allocation of federal research funding for GI research projects.

“No one has examined this for 20-30 years,” Dr. Carethers says. The Commission’s next report is due out this summer.

He also holds a two-year position as Vice Chair of the Gastrointestinal Oncology Section of the AGA. In this capacity, he reviews abstracts submitted for the annual AGA meeting. UC San Diego will serve as a host institution as this year’s AGA meeting, known as Digestive Disease Week 2008, convenes in San Diego.

Inspiring and supporting students and trainees

Today, creating ways to inspire young, motivated students is a priority for Dr. Carethers. This has inspired him to work in support of the Preuss School, UC San Diego’s charter middle and high school.

“There are students in the Preuss School who might never have gone to college if they had gone to local schools. But they come to Preuss and see that things could be different. They’re exposed to things they never knew existed.

“We have Preuss students go on to UCSD, Harvard, and other universities,” he says. “I think that’s fantastic.”

“Some people, if they’re given an opportunity, will take the ball and run with it.”

Supporting his gastroenterology students and faculty members in their development is important to him as well. He is proud of the training grant that provides protected time for Gastroenterology trainees to do research; he is delighted that the grant has just won a 5-year renewal.

“That’s how I came along,” he said. “I wouldn’t be where I am if I hadn’t had that time to develop.”

He has also established a permanent GI Division Research and Junior Faculty Development Committee to school senior fellows and junior faculty in the UC San Diego promotion process.

“It’s designed to help them navigate the academic process more smoothly,” he says. “No one tells you this stuff.”

In 2006, he received the UC San Diego School of Medicine Vice Chancellor’s Award for Mentoring Excellence.

He speaks warmly of his own mentor, C. Richard Boland, who was Chief of Gastroenterology from 1995 to 2003. Dr. Boland is now at Baylor in Dallas.

“He’s my mentor and friend for life,” he says.

“Through education, we had opportunities”

Dr. Carethers recalls the efforts of his parents, whose values carry on in him and in his siblings.

“Through education, we had opportunities,” he says. “If someone never has the opportunity, they have no idea what they’re missing. Some people never achieve because they never got the opportunity.

“But some people, if they’re given an opportunity, will take the ball and run with it.”

Today, 11 of the 12 Carethers children are college graduates. Among them, they have 21 college degrees.

More Information

Dr. John M. Carethers Elected to American Society for Clinical Investigation

Dr. John M. Carethers has been elected to the American Society for Clinical Investigation, an honorific organization of the nation’s most outstanding young physician-scientists.

Dr. John M. CarethersDr. Carethers is Professor of Medicine and Chief of the Division of Gastroenterology.

He has received numerous awards for his research in colon cancer as well as for his dedication to medical teaching.

Dr. Carethers will be introduced as a new member at the ASCI Annual Dinner to be held at the upcoming joint meeting of the ASCI and the Association of American Physicians in Chicago, April 25-27.

More Information