The ASPIRE Path in Molecular Medicine

I am currently a third year graduate student in Dr. Ken Lau’s laboratory where I study intestinal epithelial cell misspecification during inflammatory bowel disease (IBD). My work focuses on understanding how a small intestinal secretory cell subtype, known as the Paneth cells, contributes to the initiation and progression of ileal Crohn’s disease (CD), an IBD subtype. Genome-wide association studies have identified high risk alleles for CD in genes that are expressed in secretory Paneth cells. Moreover, biopsies from human CD patients have demonstrated that abnormalities in Paneth cell morphology correlate to manifestation of disease symptoms in the terminal small intestine or ileum. Despite these lines of evidence, the exact etiology of ileal CD remains unclear, as does the precise role which Paneth cells play in the disease mechanism. My thesis work will utilize a mouse model (TNFΔARE) of Crohn’s-like ileitis to understand whether Paneth cells contribute to either the initiation or progression of ileal inflammation, or both. I will also utilize single cell techniques, which our lab has developed, to analyze dysregulation of central signal transduction pathways governing Paneth cell specification and differentiation in order to elucidate the mechanisms underlying Paneth cell abnormalities during ileal inflammation. Finally, I will focus on understanding whether diminished Paneth cell secretion is a consequence of dysfunction in protein translation or post-translational processes. Cumulatively, these studies will utilize in vivo imaging, flow and mass cytometry, computational modeling, and various biochemical approaches to elucidate the mechanism of ileal inflammation.

Given my interest in IBD research, I am fortunate to have as my clinical mentor Dr. David Schwartz, M.D., Director of the Inflammatory Bowel Disease Center at the Vanderbilt Digestive Disease Center. As a physician, Dr. Schwartz treats patients suffering from various types of IBD, such as Crohn’s disease or ulcerative colitis. Though my work primarily utilizes animal models to simulate human disease, I hope to eventually collaborate with my clinical mentor to utilize patient tissue samples in my studies. Additionally, Dr. Schwartz’s expertise will be invaluable in guiding the clinical direction of my thesis research.