UC San Diego Experts Receive Grant For Crohn’s Disease Research

Crohn’s disease impacts more than 2 million people around the world and is notoriously challenging to treat. A grant of nearly $3.5 million from The Leona M. and Harry B. Helmsley Charitable Trust is supporting research at the University of California San Diego to identify better, more targeted treatments for people living with Crohn’s.

The Helmsley Charitable Trust is the largest private philanthropic organization focused on Crohn’s disease, an inflammatory bowel disease that causes chronic inflammation of the gastrointestinal tract.

The team of researchers on the study will be led by Pradipta Ghosh, MD, a professor in the UC San Diego departments of Medicine, and Cellular and Molecular Medicine. Ghosh is a physician-scientist and G protein biologist who is dually trained in cellular and molecular biology and gastroenterology and is the founding director of the UC San Diego Institute for Network Medicine.

According to Ghosh, the need for therapeutics that both reduce inflammation and address the cause of Crohn’s is both urgent and unmet. This program, she says, is motivated by a concept that is relatively new but rapidly evolving.

The team will use an “off-the-beaten-path” computational approach that identifies invariant relationships between gene expression and disease state. The method has a proven track record of identifying pathological cell states that are fundamentally important disease drivers.

In this work, Ghosh is employing that approach to identify among Crohn’s patients the most druggable G protein-coupled receptors, or GPCRs, which are the target of approximately 40% of all currently marketed drugs—treating everything from hypertension to asthma to glaucoma—but currently are underutilized in the treatment of inflammatory bowel diseases.

During the course of studies in her laboratory, Ghosh and her team identified how GPCRs may be contributing to IBD, and more specifically, Crohn’s disease. Results indicate how this target class could be maximally exploited as pharmacologic targets. Microbes in the dysbiotic gut of Crohn’s disease patients produce metabolites, some of which are known to cause abnormal GPCR signaling and impact the magnitude of inflammation. Ghosh believes that drugs targeting the GPCRs could “reset” these abnormal signals, restore gut health and ultimately lead to better tests and more effective treatments for Crohn’s disease.

“To drive high-risk, high-gain programs such as this, it is vital that experts from numerous disciplines work together to tackle and solve complex problems. It is also vital to have creative freedom and funding to test concepts and approaches that have never been tried before,” said Ghosh. “At the Institute for Network Medicine, we consistently engage in this type of work thanks to funders such as the Helmsley Charitable Trust.”

Ghosh is joined in the effort by team members including Brigid Boland, MD, assistant professor of medicine; Debashis Sahoo, MD, associate professor of pediatrics, and computer science and engineering; and Courtney Tindle, program manager and director of operations at the UC San Diego HUMANOID Center of Research Excellence (CoRE).