Alexander Gitlin, M.D., Ph.D.

Research

My lab explores how cell signaling controls the nature and magnitude of inflammation in normal physiology and in disease, focusing on the intersection of inflammatory signaling and cell death pathways. The links between inflammation and cancer have long been appreciated but remain poorly understood. For example, nearly 20% of patients with inflammatory bowel disease (IBD) will eventually develop colitis-associated colorectal cancer. The mechanisms responsible for phenomena such as this remain enigmatic. We hypothesize that the mechanisms by which inflammatory signals like toll-like receptors (TLRs) or tumor necrosis factor (TNF) promote or suppress cell death may contribute to cancer formation in people who have conditions like IBD. Understanding the mechanisms that determine whether inflammation promotes or fights cancer could lead to the discovery of therapies that minimize the tumor-promoting effects of inflammation while harnessing its anticancer benefits. However, studying the spatiotemporal mechanisms involved has been challenging due to the confounding effects that occur when key inflammatory pathways are genetically perturbed in mice. To overcome these challenges, we will use a sophisticated system of conditional, mosaic gene mutagenesis to manipulate inflammation-associated cancer and cell death clonally within rare cells in vivo. This work will identify key cellular circuits that spatiotemporally influence the progression of inflammation-associated cancer, identifying new strategies that may be targeted for cancer therapy.