Inflammatory bowel disease is an umbrella term for a group of debilitating, chronic, and difficult to treat diseases that affect millions worldwide. In these diseases, intestinal fibroblasts acquire immunoregulatory roles and establish detrimental interactions with immune cells that contribute to therapy resistance. However, the mechanisms governing this remain poorly understood. My lab identified an epigenetically-coded memory program in fibroblasts from resections of therapy-resistant IBD patients. This could be induced In vitro by exposing healthy fibroblasts to cytokine stimulation, and resulted in altered responses to subsequent bouts of inflammation. We hypothesize that epigenetically-coded memory modulates fibroblast pathogenicity in IBD. The proposed PhD project will explore: 1)Mechanisms that mediate the acquisition of epigenetic memory in intestinal fibroblasts; And, 2) Their impact in fibroblast-myeloid cell interaction.

Inflammatory bowel disease is an umbrella term for a group of debilitating, chronic, and difficult to treat diseases that affect millions worldwide. In these diseases, intestinal fibroblasts acquire immunoregulatory roles and establish detrimental interactions with immune cells that contribute to therapy resistance. However, the mechanisms governing this remain poorly understood. My lab identified an epigenetically-coded memory program in fibroblasts from resections of therapy-resistant IBD patients. This could be induced In vitro by exposing healthy fibroblasts to cytokine stimulation, and resulted in altered responses to subsequent bouts of inflammation. We hypothesize that epigenetically-coded memory modulates fibroblast pathogenicity in IBD. The proposed PhD project will explore: 1)Mechanisms that mediate the acquisition of epigenetic memory in intestinal fibroblasts; And, 2) Their impact in fibroblast-myeloid cell interaction.