The mission of this Pilot Grant Award Program is to promote research aimed at understanding how the innate immune system molds the gastrointestinal and hepatic environment and how these processes influence organ function, mucosal immunity, innate host defense, acute and chronic inflammation/cancer, and microbial pathogenesis.
As a physician scientist Dr. Cara Mack has focused her research studies on immune-mediated liver diseases, with a vested effort on deciphering the role of the immune system in the pathogenesis of biliary atresia (BA). The etiology of BA is unknown and the chronic biliary damage ultimately results in cirrhosis and the need for liver transplantation in the vast majority. Her scientific training occurred under the mentorship of Stephen Miller, PhD, an expert in autoimmunity. For the past 14 years she has established strong collaborations with immunologists from the Departments of Immunology and Medicine (Division of Allergy & Clinical Immunology) at the University of Colorado. Her group has made significant inroads into the mechanisms of T and B cell-mediated inflammation and autoimmunity in BA. They were the first to identify autoreactive T cells specific to bile duct epithelial proteins in the mouse model of BA and oligoclonal expansions of T cells in human BA. Their current project focuses on the role of B cells and humoral immunity in the pathogenesis of BA. They were the first to characterize autoantibodies in both mouse and human BA and to show that mice deficient in B cells were protected from developing BA. These studies imply critical roles for both T and B cells in the immunopathogenesis of BA. Her clinical research efforts include clinical and translational studies pertaining to diagnosis and outcomes in BA and other pediatric liver diseases, through the NIH-funded Childhood Liver Disease Research Network (ChiLDReN). The overarching goal of her research endeavors is to utilize her immunology expertise to explore the mechanisms underlying the pathogenesis and treatment of immune-mediated pediatric biliary and liver diseases. Finally, she has made it a priority in her career to mentor junior investigators and instill the passion of pursuing a career as a physician scientist. To that end, she recently was awarded a NIH T32 grant renewal as a Co-PI with Dr. Ronald Sokol, MD and she is the Pediatric Fellowship Program Director within her section.