Laboratory of Mucosal Immunology
The Rockefeller University
At the surface of the intestinal lining, immune responses are carefully balanced: Invasive pathogens and cancers must be eliminated or excluded, while nutrients and trillions of commensal microbes must be tolerated. I study how the immune system associated with intestinal mucosae maintains this careful balance by generating efficient protective and anti-tumor responses without jeopardizing its tolerance to innocuous foreign substances.
Dr. Mucida received his undergraduate degree in biology, with an emphasis on biochemistry and immunology, from the Federal University of Minas Gerais in Brazil in 2000. He received his Ph.D. jointly from the University of São Paulo and New York University in 2005. After postdoctoral studies at the La Jolla Institute for Allergy and Immunology from 2006 to 2010, he joined The Rockefeller University as assistant professor and head of the Laboratory of Mucosal Immunology. In 2016, he was promoted to Associate Professor. Dr. Mucida studies how the immune system associated with intestinal mucosae is able to generate efficient immune responses without jeopardizing its tolerance to innocuous antigens. For his work he received several awards including New Scholar Award from the Ellison Foundation, the Career Development Award from The Crohn’s and Colitis Foundation of America, the Irma T. Hirschl/Monique Weill-Caulier Trust Research Award, the Gabrielle H. Reem and Herbert J. Kayden Early-Career Innovation Award, the NIH Director’s Transformative Research Award, the Society for Mucosal Immunology Young Investigator Award.
Role of intraepithelial lymphocytes in colon cancer
Colorectal cancer (CRC) is one of the most common and deadly cancers in the US. CRC arises in the large intestine, where a single layer of epithelial cells separates the microbe and dietary metabolite-rich intestinal lumen from the core of the body. A large population of immune cells called intraepithelial lymphocytes (IELs) reside at this barrier and are thought to play a role in preventing infection. We recently used new imaging techniques and genetic approaches to access and interfere with IELs in live animals, showing that IELs constantly surveil the intestinal epithelial surface, regulating bacterial invasion. However, the role of IELs, as well as of the microbiota, in CRC has not been studied in detail.
“The Pershing Square Sohn Prize will allow a better understanding of adaptive immunity at the gut epithelial barrier, contributing valuable information regarding host-microbial interactions and cancer, and possibly revealing new targets for immunotherapy intervention.”
Patients with chronic inflammatory diseases have a 3 to 5-fold increased risk of CRC compared to the general population. Nevertheless, most CRCs develop in patients without underlying inflammation, triggered by epithelial loss of tumor suppressor genes. In both cases of CRC, tumor-elicited inflammation triggers epithelial cell damage resulting in invasion by microbes, in turn driving tumor growth by sustaining inflammation. Therefore, immune surveillance of the epithelial barrier may help prevent damaged epithelial cells from progressing into cancer. We hypothesize intestinal IELs constantly survey the epithelial layer, killing transformed epithelial cells. By utilizing novel imaging tools, we will analyze IEL interactions with the healthy or transformed epithelium in the intestine of live animals. Using genetic approaches targeting IELs, we will establish their role in sensing transformed epithelial cells, revealing new targets for immune-therapies.
“Our innovation stands from combining gene-reporters and multiple cell-specific and temporally controlled gene targeting approaches with in vivo imaging strategies in models of epithelial damage, inflammation and CRC. By addressing epithelial-immune cell interactions in vivo, we expect to dissect the function of the T cells that constantly scan the intestinal surface.”
Daniel Mucida is a Pershing Square Sohn Prize Mathers Foundation Fellow. His project is funded in an exciting partnership with The G. Harold and Leila Y. Mathers Foundation, which aims to advance knowledge in the life sciences by sponsoring scientific research that will benefit mankind. Basic scientific research, with potential translational application, is central to this goal, and fundamental to its operating principles. For more information, please refer to the full press release.