Atul K. Bhan, MBBS, MD
Professor of Pathology, Harvard Medical School
Pathologist, Massachusetts General Hospital
Massachusetts General Hospital
55 Fruit Street
Warren Building, Room 501
Boston, MA 02114
Explore This Lab
About the Lab
In the two major forms of inflammatory bowel disease (IBD), Crohn’s disease and ulcerative colitis, the underlying etiological factors and the pathogenesis remain poorly defined. It is generally believed that exaggerated immune responses to luminal normal enteric flora are involved in the initiation and perpetuation of the disease process.
The availability of a wide variety of experimental models of intestinal inflammation has helped provide important clues about the pathogenesis of IBD. The commonly used models include chemically induced mucosal injury and colitis induced by the transfer of selected populations of T cells into immunodeficient mice. The spontaneous development of colitis in genetically engineered animal models has provided excellent experimental models to study
the pathogenesis of IBD. One important lesson learned from IBD models is that many different immunologic and mucosal defects can lead to similar pathologic findings.
Our laboratory defined the pathogenesis of chronic intestinal inflammation using TCR alpha KO mice as a model of human IBD. TCR alpha KO mice develop spontaneously chronic colitis with many features of ulcerative colitis. We identified a regulatory B cell subset, which appears under chronic intestinal inflammatory conditions and suppresses the progression of intestinal inflammation by secreting IL-10. TCR alpha KO mice deficient in both IL-4 and B cells, but not in IL-4 alone, develop granulomatous colitis with features of Crohn’s disease. This suggests that differences in the two major forms of IBD may reflect different immunological responses to similar initiating events.
The laboratory is closely associated with the Center for the Study of Inflammatory Bowel Disease at MGH and collaborates with the other members of the Center; Dr. Bhan is an Associate Director of the Center. In collaboration with Dr. Terhorst and Dr. Xavier we have studied the role of Th-1 and Th-17 pathways, innate immune system and autophagy in the development of intestinal inflammation. Collaborative studies with Dr. Scott Snapper’s laboratory have shown that interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function. The studies with Dr. Richard Hodin’s laboratory indicate that administration of intestinal alkaline phosphatase may have a beneficial effect in intestinal inflammatory conditions and metabolic syndromes.
Immune cells acquire unique, functionally important molecules depending on their anatomical localization and local environment. A monoclonal antibody (Act-1), developed in collaboration with Dr. Colvin’s and Dr. Kurnick’s labs, was found to be reactive with a4b7integrin, the gut homing receptor that recognizes the mucosal-associated address in MAdCAM-1 on endothelial cells. This antibody has been humanized (renamed Vedolizumab or Entyvio and marketed by Takada Pharmaceuticals) and is currently being used for the treatment of Crohn’s disease and ulcerative colitis.
Mohanan V, Nakata T, Desch AN, et al. C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions. Science 2018; 359:1161-1166.
Lassen KG, McKenzie CI, Mari M, et al. Genetic coding variant in GPR65 alters lysosomal pH and links lysosomal dysfunction with colitis risk. Immunity. 2016; 44:1392-405.
Lassen KG, Kuballa P, Conway KL, et al. Atg16L1 T300A variant decreases. Selective autophagy resulting in altered cytokine signaling and decreased antibacterial defense. Proc Natl Acad Sci USA. 2014; 111:7741-6.
Shouval DS, Biswas A, Goettel JA, et al. Interleukin-10 Receptor Signaling in Innate Immune Cells Regulates Mucosal Immune Tolerance and Anti-Inflammatory Macrophage Function. Immunity. 2014; 40:706-19.
Kaliannan K, Hamarneh SR, Economopoulos KP, et al. Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proc Natl Acad Sci USA. 2013; 110:7003-8.
Chang SY, Song JH, Guleng B, et al.Circulatory antigen processing by mucosal dendritic cells controls CD8+ T cell. Immunity. 2013; 38:153-165.
Yilmaz OH, Katajisto P, Lamming DW, et al. mTORC1 in the Paneth cell niche couples intestinal stem cell function to calorie intake. Nature. 2012; 486:490-5.
Mizoguchi A, Ogawa A, Takedatsu H, et al. Dependence of intestinal granuloma formation on unique myeloid DC-like cells. . J Clin Invest. 2007; 117:605-615.
Lazarovits AI, Moscicki RA, Kurnick JT, et.al. Lymphocyte activation antigens. I. A monoclonal antibody, anti-Act I, defines a new late lymphocyte activation antigen. J Immunol 1984; 133:1857-1862.
- Pathologist, Massachusetts General Hospital
- Professor of Pathology, Harvard Medical School
Pathology Research activities occupy approx. 20,000 sq.ft., with researchers receiving over $19 million in direct costs of annual research support
Pathology Basic Science Research Brochure
The Pathology Basic Science Research Brochure brochure highlights the basic scientific research activities in MGH Pathology.