Mahima Swamy's Research Group

Pubmed | Biography


Immune interactions at the intestinal epithelium

Inflammatory bowel diseases (IBD) and colon cancer are both diseases involving the intestinal epithelium, the single layer of epithelial cells that serves dual functions of nutrient absorption and protection from the external environment. The epithelial layer also contains a complex and unconventional pool of T cells collectively called intraepithelial lymphocytes (IEL). These IEL patrol the epithelial layer, and are tasked with eliminating infected, damaged or transformed epithelial cells. IEL are required for regulating the viral, bacterial, and parasite loads in the gut, and are even capable of preventing infection completely (Swamy et al., 2010, 2015). Despite their importance, we understand very little of how these cells are activated, or their mechanisms of action.

Research in my lab focuses on the fundamental roles of IEL in coordinating responses to chemical, dietary and microbial inputs, either directly, or indirectly through intestinal epithelial cells. Our group studies the signaling pathways that activate intestinal IEL to mediate epithelial cell death and/or repair. We use a combination of biochemistry, proteomics, transgenic mouse models, and in vivo infection studies.

In recent work, we have measured and quantified the complete proteomes of primary intestinal epithelial cells and IEL using high resolution mass-spectrometry. We are using these data to identify and characterize molecular interactions between IEL and intestinal epithelial cells. Ultimately, we hope to have a better understanding of how IEL contribute to intestinal homeostasis in health and disease.

People

Yu Chen | Postdoctoral Scientific Officer

Selected Publications

Swamy M, Beck-Garcia K, Beck-Garcia E, Hartl FA, Morath A, Yousefi OS, Dopfer EP, Molnár E, Schulze AK, Blanco R, Borroto A, Martín-Blanco N, Alarcon B, Höfer T, Minguet S, Schamel WW. (2016) A Cholesterol-Based Allostery Model of T Cell Receptor Phosphorylation Immunity May 17;44(5) 1091-101. doi: 10.1016/j.immuni.2016.04.011
Swamy, M., Pathak, S., Grzes, K. M., Damerow, S., Sinclair, L. V., van Aalten, D. M., Cantrell, D. A. (2016) Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy Nat Immunol 17 712-20
Swamy M, Abeler-Dörner L, Chettle J, Mahlakõiv T, Goubau D, Chakravarty P, Ramsay G, Reis e Sousa C, Staeheli P, Blacklaws BA, Heeney JL, Hayday AC. (2015) Intestinal intraepithelial lymphocyte activation promotes innate antiviral resistance Nat Commun. 19 6:7090. doi: 10.1038/ncomms8090
Molnar, E.*, Swamy, M.*, Holzer, M., Beck-García, K., Worch, R., Thiele, C., Guigas, G., Boye, K., Luescher, I.F., Schwille, P., et al. (2012) Cholesterol and sphingomyelin drive ligand-independent T-cell antigen receptor nanoclustering J Biol Chem 287 42664:42674
Bas, A., Swamy, M., Abeler-Dörner, L., Williams, G., Pang, D.J., Barbee, S.D., and Hayday, A.C. (2011) Butyrophilin-like 1 encodes an enterocyte protein that selectively regulates functional interactions with T lymphocytes. Proc Natl Acad Sci USA 108 4376:4381
Swamy, M., Jamora, C., Havran, W., and Hayday, A. (2010) Epithelial decision makers: in search of the 'epimmunome' Nat Immunol 11 656:665