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2027 Scholar-Innovator and ADDF-Harrington
Inflammation, Gastroenterology, Transplantation
Small Molecule Inhibitors of CD40 for the Treatment of Inflammatory Disorders
2024 Harrington Scholar-Innovator
A major advance in the treatment of inflammatory/autoimmune disorders may come from an unlikely source. Dr. Subauste is an infectious disease specialist who was studying intracellular parasites when his lab made discoveries that may lead to new treatments for patients with autoimmune disorders.
“My work has always been in infectious diseases and immune response, and now my lab is developing a drug for treating inflammatory bowel disease (IBD),” Dr. Subauste says. “That’s why science is so exciting. You never know what paths you’re going to follow and where they will lead you.”
Dr. Subauste explains that a protein called CD40 plays a crucial role in the immune system. Expressed by many cell types, CD40 is required for protection against many pathogens. When CD40 is overactive, however, it drives inflammatory and autoimmune disorders such as IBD.
Dr. Subauste and his colleagues identified a small molecule (CCI2260) that blocks a specific pathway downstream of CD40, reducing pro-inflammatory responses without affecting mechanisms of protection against pathogens. It diminishes intestinal inflammation in mouse models of IBD and does not make mice susceptible to an opportunistic pathogen.
With the support of Harrington Discovery Institute, Dr. Subauste proposes to expand his team’s efforts to develop an optimized inhibitor and a biomarker that will be used in subsequent in vivo studies.
“I’m not an IBD expert and have never attempted direct drug development,” he says, “but the purpose of my work is helping patients, and I absolutely would consider my career to have been fulfilling if I were able to create a new drug for the treatment of autoimmune disorders.”
"I am very impressed by the high caliber of the scientists that are members of the Harrington team. I find their input to be extremely helpful, and I believe it is accelerating the progress of the grant."