Dr. Gregory F. Sonnenberg, The Henry R. Erle, M.D.-Roberts Family Associate Professor of Medicine and head of basic research in the division of Gastroenterology and Hepatology in the Weill Department of Medicine, has been awarded a $3.26 million, five-year MERIT grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to investigate the underlying causes of inflammatory bowel disease (IBD).
The new grant, which has the possibility of extension for five additional years, will fund research on a novel pathway that protects the intestine from damage and inflammation driven by an immune-derived factor called tumor necrosis factor (TNF).
“It’s a huge honor to be considered and nominated for a NIH MERIT award, and such a privilege to be able to move this research forward with my laboratory over an extended period of time,” Dr. Sonnenberg said.
The MERIT program, a backronym for “Method for Extending Research In Time,” gives investigators with stellar records of research accomplishment a five-year award with the possibility of extending the initial award for up to five additional years without the need to undergo another competitive peer review.
Dr. Sonnenberg’s proposal was based on research his laboratory pioneered over the past decade characterizing key immune cell pathways in the intestine. It’s one of the major mysteries in the field. “TNF is normally beneficial, but what causes this shift for it to become a major mediator of chronic inflammatory diseases?” asked Dr. Sonnenberg, who is in the Division of Gastroenterology & Hepatology in the Weill Department of Medicine and a member of the Jill Roberts Institute for Research in Inflammatory Bowel Disease at Weill Cornell Medicine.
The Sonnenberg lab, with Dr. Greg Sonnenberg, seated second from right.
Many current therapies block TNF to reduce inflammation in chronic inflammatory diseases, including IBD, rheumatoid arthritis and psoriasis, but those treatments are only effective in a subset of patients, and even if successful, this therapy can lose efficacy over time. Dr. Sonnenberg’s team discovered that TNF-induced gut inflammation correlates with the depletion of group 3 innate lymphoid cells (ILC3s), a special class of cells abundant in the healthy intestine. “This provoked a hypothesis that these cells are keeping the TNF molecule in check and stopping it from driving tissue inflammation,” Dr. Sonnenberg said.
Experiments published last year in preclinical models confirmed that hypothesis and revealed that ILC3s are essential to protect the intestine from TNF-mediated damage and inflammation, which the team will explore further with support of this MERIT Award. Dr. Sonnenberg and his laboratory proposed a series of experiments to define the cellular and molecular signals by which ILC3s protect from TNF-induced inflammation. He also plans to investigate this pathway in both mouse models and patient-based organoids, complex human cell culture systems that model the guts of healthy individuals or patients with IBD.
Related: WCM Newstory