Principal Investigator: Vasilios Kalas, MD, PhD, Physician-Scientist Training Program Fellow, Division of Gastroenterology and Hepatology, Northwestern Medicine, Northwestern University Feinberg School of Medicine

Co-Principal Investigator: Gabriel Rocklin, PhD, Assistant Professor of Pharmacology, Northwestern Medicine, Northwestern University Feinberg School of Medicine

Inflammatory bowel disease (IBD) develops from interactions between gut microbes and genetic risk factors that trigger an out-of-control immune response. The health of some 2.5 million Americans heavily depends on IBD drugs to reduce gut inflammation and prevent infection. Unfortunately, the medications don’t work for one-third of patients and for up to 50 percent of individuals, currently available IBD drugs lose their effectiveness over time. Innovating new therapies is critical to expanding and improving life-enhancing treatment options for patients.

A human protein, TNF (tumor necrosis factor) plays a key role in driving gut inflammation. Large injectable antibody drugs, like Humira and Stelara, effectively target TNF but, in the process, they block both good (TNF receptor-2) and bad (TNF receptor 1) pathways. Thanks to previous work supported by DHF, Dr. Kalas’ team has used artificial intelligence to create thousands of unique synthetic miniproteins to specifically block TNFR1. Their small size allows for the development of transformative medication easily taken by mouth. Funded by this year’s DHF award, the team plans to test the most promising of these engineered TNFR1-selective miniproteins inhibitors in animal models and human samples of IBD. This exciting research presents a great opportunity to offer millions of IBD patients an effective and convenient oral (vs infusion or injection) treatment.