Simmons Conference: Dr. Anna Ramos, "Targeting the mitochondrial life cycle in the colonic epithelium to alleviate colitis"

Dr. Anna Ramos, MD

Title: "Targeting the mitochondrial life cycle in the colonic epithelium to alleviate colitis"

Although the pathogenesis of ulcerative colitis is multifactorial, including abnormal innate and adaptive immune responses, epithelial barrier dysfunction, and gut dysbiosis, most therapeutic interventions focus solely on the modification of the immune system. Immunomodulatory and biological agents have had proven clinical benefits, but rates of disease relapse eventually mandating therapeutic change or operative intervention remain high. Focusing on complementary mechanisms underlying human IBD, such as disruption of the intestinal epithelium, could provide significant benefits in treatment. Maintenance of the epithelial barrier is an energy-dependent process that relies on mitochondrial viability. However, IBD patients have demonstrated increased susceptibility to gut mitochondrial damage and dysfunction. Mitophagy is a quality-control mechanism that selectively removes dysfunctional mitochondria. Multiple mitophagy pathways co-exist in the intestine, including the canonical PINK1/PARKIN and NIX pathways. We hypothesize that mitophagic flux represents a key homeostatic response to intestinal epithelial inflammation and is a potential therapeutic target.

Mentors: Dr. Kevin Mollen & Dr. Sidrah Khan