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Much of the current understanding of the pathogenesis underlying inflammatory bowel disease (IBD) comes from studies using animal models. To date, it appears that IBD develops due to a genetic predisposition resulting in altered immune response to the intestinal microbiome. My laboratory is interested in how the actin network regulates mucosal immune homeostasis. We initially focused our studies on the spontaneous colitis that occurs in mice deficient in Wiskott-Aldrich Syndrome Protein (WASP), an intracellular hematopoietic cell-specific protein that regulates actin polymerization, which is essential for numerous immune cell functions. This serves as one of the few animal models of IBD with a human correlate, since some patients with Wiskott-Aldrich Syndrome also develop colitis. We found that lack of functioning WASP leads to deficiencies in T cell activation and chemotaxis, quantitative and qualitative defects in regulatory T cells, aberrant education of T cells by innate immune cells (partially through defective production of interleukin-10), and spontaneous CD4+ T cell-mediated intestinal inflammation that is associated with a skewed Th2-cytokine profile. This led to the overall question of whether mucosal dysregulation in these mice stems from defects in actin remodeling. My laboratory is now interested in studying other regulators of actin polymerization and bundling, such as Rac and L-plastin, in controlling intestinal immune balance.
The goal of my research is to elucidate the pathogenesis underlying the development of inflammatory bowel disease in the hopes of identifying novel therapeutic targets. In addition, as a physician at the MGH Crohn’s & Colitis Center and a co-investigator in PRISM (Prospective Registry of Inflammatory Bowel Disease Study at MGH), I am also interested in identifying novel serum and urine biomarkers of inflammatory bowel disease and identifying rare but highly penetrant genetic variants associated with risk for inflammatory bowel disease, specifically ulcerative colitis. Lastly, I also participate in clinical trials of novel therapies and take part in a national study on the safety of commonly used medications for inflammatory bowel disease during pregnancy.
Dr. Deanna Nguyen is currently Instructor in Medicine at Harvard Medical School. Her interest in mucosal immunology research began in high school under the mentorship of Dr. Richard Hodin (Professor of Surgery at Harvard Medical School), and continued at Harvard College and Harvard Medical School. She then completed her postdoctoral training under Dr. Scott Snapper (Associate Professor in Medicine at Harvard Medical School) during gastroenterology fellowship and advanced fellowship in inflammatory bowel disease at Massachusetts General Hospital. In 2008, she came on staff at MGH as attending physician in the Crohn’s and Colitis Center and investigator in the Center for the Study of Inflammatory Bowel Disease.
Deanna Nguyen, M.D.Gastrointestinal UnitJackson 815Massachusetts General Hospital55 Fruit St, Boston, MA 02114Office: 617-724-2047Fax: 617-726-3080
Yan Song, Ph.D.
Romela Marin, B.S.
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