Principal Investigator: Vasilios Kalas, MD, PhD, Physician-Scientist Training Program Fellow (PGY-4), Division of Gastroenterology and Hepatology, Northwestern Medicine, Northwestern Feinberg School of Medicine

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

Inflammatory bowel disease (IBD) affects the lives of more than 2.5 million Americans, including many children and adolescents. A serious, chronic autoimmune disease, IBD is characterized by the body’s immune system going into overdrive and attacking its own tissue, causing gut inflammation and infection, diarrhea, rectal bleeding, and bowel obstructions. IBD drugs help tamp down the inflammation, but they also can weaken the immune system. This broad swipe approach to treatment, in combination with the disease, can leave patients vulnerable to infection and cancers.

The molecular structure of IBD medications plays a major role in their effectiveness. While small molecules make therapeutics like prednisone an easy-to-swallow oral drug, these drugs typically have low potency because they are unable to target the unique inflammatory causes of a patient’s IBD. On the other hand, large antibody drugs, like Humira or Stelara, offer higher potency and specificity, but they must be injected or infused at a clinic. Supported by this year’s DHF grant, Dr. Kalas’ team plans to use advances in artificial intelligence (AI) to engineer a new kind of drug molecule that has both high potency AND high specificity, and can also be easily taken by mouth. The investigators will create miniprotein blockers that target the receptors TNFR1 and claudin-2 that cause IBD inflammation. This revolutionary research aims to develop more effective oral therapies with fewer side effects that could be a gamechanger for patients with IBD who have limited options with current treatments.