Kirk Bergstrom

Assistant Professor

Biology

Office: ASC 373
Phone: 250.807.8696
Email: kirk.bergstrom@ubc.ca

Research Summary

Host-microbiota interactions; Glycobiology

Courses & Teaching

BIOL420 Functional Glycoscience; BIOL314 Medical Microbiology

Degrees

BSc, University of Northern British Columbia
PhD, University of British Columbia

Research Interests & Projects

Regulation of host-microbiota symbiosis by intestinal mucin-type O-glycosylation

Our gastrointestinal (GI) tract represents perhaps the most “contaminated” environment our bodies could encounter, being home to ~ 10 trillion microbes across thousands of species, collectively termed the “commensal microbiota”. Incredibly, despite their close association with our tissues, our bodies normally not only tolerate these microbes (mostly bacteria), but require them for proper development and function of the GI tract, and even beyond. However, in some cases, this mutualistic interaction fails, leading potentially to disease.

My field of interest is focused on mechanisms of innate immunity in the gastrointestinal tract that promote protective responses against pathogens, while preventing unwanted inflammatory responses to our resident microbiota. Specifically, my research centers on the intestinal mucus system, a network of glycoproteins manufactured and secreted by goblet cells, and how defects in this system contribute to susceptibility to infections, inflammatory bowel disease (IBD), and colon cancer. To study this, I employ a repertoire of specialized skills to probe host-microbiota interactions in disease causation at the organismal, tissue, cellular and molecular level, including functional analysis of mucins and glycan biology, gut ecology; and state-of-the-art imaging and genetic modeling. Using these approaches (during my postdoctoral training at Oklahoma Medical Research Foundation) has led to novel insights into how the intestine utilizes two key glycosyltransferases, Core-1 β1,3 galatactosyltransferase (Core 1 synthase) and Core 3 β1,3N-acteylglucosaminyltransferase (Core 3 synthase), which decorate mucin proteins with sugars (aka glycans), to promote optimal mucus function that keeps the microbiota at a “healthy distance” from the gut, and prevent spontaneous IBD, as well as cancers of the colon and small intestine.

My independent studies build directly on this work, where I am addressing how the expression and activity of Core 1- and 3- synthases are controlled in humans and preclinical murine model systems; how mucin-type O-glycans impact the structure and function of microbial communities in the gut, and how O-glycans regulate formation and function of the intestinal mucus system. The goals of this work aim to increase our knowledge of the fundamental roles of mucins and their O-glycans in the gut, and devise novel methods of intervention to boost their protective capacities in IBD and cancer patients where defects in these systems are thought to contribute to pathogenesis.

Selected Publications & Presentations

Bergstrom K,* Xia L.* 2022. The barrier and beyond: Roles of intestinal mucus and mucin-type O-glycosylation in resistance and tolerance defense strategies guiding host-microbe symbiosis. Gut Microbes. 14(1):2052699. PMID:35380912

Mirzayi C, Renson A, Genomic Standards Consortium Massive Analysis Quality Control, Society,  Zohra F, Elsafoury S, Geistlinger L, Kasselman LJ, Eckenrode K, van de Wijgert J, Loughman A, Marques FZ, MacIntyre DA, Arumugam M, Azhar R, Beghini F, Bergstrom K, Bhatt A, Bisanz JE, Braun J, Bravo HC, Buck GA, Bushman F, Casero D, Clarke G, Collado MC, Cotter PD, Cryan JF, Demmer RT, Devkota S, Elinav E, Escobar JS, Fettweis J, Finn RD, Fodor AA, Forslund S, Franke A, Furlanello C, Gilbert J, Grice E, Haibe-Kains B, Handley S, Herd P, Holmes S, Jacobs JP, Karstens L, Knight R, Knights D, Koren O, Kwon DS, Langille M, Lindsay B, McGovern D, McHardy AC, McWeeney S, Mueller NT, Nezi L, Olm M, Palm N, Pasolli E, Raes J, Redinbo MR, Ruhlemann M, Balfour Sartor R, Schloss PD, Schriml L, Segal E, Shardell M, Sharpton T, Smirnova E, Sokol H, Sonnenburg JL, Srinivasan S, Thingholm LB, Turnbaugh PJ, Upadhyay V, Walls RL, Wilmes P, Yamada T, Zeller G, Zhang M, Zhao N, Zhao L, Bao W, Culhane A, Devanarayan V, Dopazo J, Fan X, Fischer M, Jones W, Kusko R, Mason CE, Mercer TR, Sansone SA, Scherer A, Shi L, Thakkar S, Tong W, Wolfinger R, Hunter C, Segata N, Huttenhower C, Dowd JB, Jones HE, Waldron L. 2021. Reporting guidelines for human microbiome research: the STORMS checklist. Nat Med. 27(11):1885-1892. PMID:34789871

Liu F,^† Fu J,^† Bergstrom K,^† Shan X, McDaniel JM, McGee S, Bai X, Chen W,* Xia L.* 2020. Core 1-derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer. J Exp Med. 217(1):e20182325. PMID:31645367

Bergstrom K,*^† Shan X,^† Casero D, Batushansky A, Lagishetty V, Jacobs JP, Hoover C, Kondo Y, Shao B, Gao L, Zandberg W, Noyovitz B, McDaniel JM, Gibson DL, Pakpour S, Kazemian N, McGee S, Houchen CW, Rao CV, Griffin TM, Sonnenburg JL, McEver RP, Braun J, Xia L.* 2020. Proximal colon-derived O-glycosylated mucus encapsulates and modulates the microbiota. Science. 370(6515):467-472. PMID:33093110

Yi, J.†, Bergstrom, K.†, Fu, J., Shan, X., McDaniel, J.M., McGee, S., Qu., D., Houchen, C.W., Liu, X.*, Xia, L.* 2018. Dclk1 in tuft cells promotes inflammation-driven epithelial restitution and mitigates chronic colitis. Cell Death and Differentiation; in press (published Nov. 26, 2018).

Song, K.†, Fu, J.†, Song, J., Herzog, B.H., Bergstrom, K., Kondo, Y., McDaniel J.M., McGee S., Silasi-Mansat, R., Lupu, F., Chen, H., Bagavant, H., Xia, L. 2017. Loss of mucin-type O-glycans impairs the integrity of the glomerular filtration barrier in the mouse kidney. Journal of Biological Chemistry 292(40):16491-16497.

Bergstrom, K.†, Liu, X.†, Zhao, Y.†, Gao, N., Wu, Q., Song, K., Cui, Y., Li, Y., McDaniel, J.M., McGee, S., Chen, W., Huycke, M.M., Houchen, C.W., Zenewicz, L.A., West, C.M., Chen, H., Braun, J., Fu, J.*, Xia, L.* 2016. Defective intestinal mucin-type O-glycosylation causes spontaneous colitis-associated cancer in mice. Gastroenterology 151(1):152-64 e11.

Bergstrom, K., Fu. J., Johansson, M.E., Liu. X., Gao, N., Wu, Q., Song, J., McDaniel. J.M., McGee, S., Chen, W., Braun, J., Hansson G.C., Xia, L. 2016. Core 1- and 3-derived O-glycans collectively maintain the colonic mucus barrier and protect against spontaneous colitis in mice. Mucosal Immunology 10(1):91-103. Epub 2016 May 4.

Bergstrom, K.†, Gao, N.†, Fu, J., Xie, B., Chen, W., and Xia, L. 2016. Loss of intestinal O-glycans promotes spontaneous duodenal tumors. American Journal of Physiology-Gastrointestinal and Liver Physiology 311(1):G74-83.

Bergstrom, K.†, Morampudi, V.†, Chan, J.M., Bhinder, G., Lau, J., Yang., H., Ma, C., Huang, T., Ryz, N., Sham, H.P., Zarepour, M., Zaph, C., Artis, D., Nair, M.G., and Vallance, B.A. 2015. Goblet cell derived RELM-β Recruits CD4+ T cells during infectious colitis to promote protective intestinal epithelial cell proliferation. PLoS Pathogens 11(8): e1005108.

Song, K.†, Herzog, B.H.†, Fu, J., Sheng, M., Bergstrom, K., McDaniel J.M., Kondo, Y., McGee, S., Cai, X., Li, P., Chen, H.*, and Xia, L.* 2015. Loss of Core 1-derived O-glycans decreases breast cancer development in mice. Journal of Biological Chemistry 290(33): 20159-66.

Bergstrom, K.†, Perez-Munoz, M.†, Peng, V., Schmaltz, R., Jimenez-Cardona, R., Marsteller, N., McGee, S., Clavel, T., Ley, R., Xia, L. *, and Peterson D.* 2014. Discordance between changes in the gut microbiota and pathogenicity in a mouse model of spontaneous colitis. Gut Microbes 5(3): 286-95.

Bergstrom, K., Fu, J., and Xia, L. 2014. Biological functions of C1GalT1 and mucin-type O-glycans. In Glycoscience: Biology and Medicine. N. Taniguchi, T. Endo, G.W. Hart, P.H. Seeberger, and C.H. Wong, editors: Springer Japan. 1073-1080.

Bergstrom, K., and Xia, L. 2013. Mucin type O-glycans and their roles in intestinal homeostasis. Glycobiology 23(9):1026-1037.

Bergstrom, K., Kissoon-Singh, V., Gibson, D.L., Ma, C., Montero, M., Sham, H.P., Ryz, N., Huang, J.T., Velcich, A., Finlay, B.B., Chadee, K., and Vallance, B.A. 2010. Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa.  PLoS Pathogens 6(5): e1000902.

Bergstrom, K.†, Guttman, J.A.†, Rumi, M.A., Ma, C., Bouzari, S., Khan, M.A., Gibson, D.L., Vogl, W.A., and Vallance, B.A. 2008. Modulation of intestinal goblet cell function during infection by an attaching and effacing bacterial pathogen. Infection and Immunity 76(2):796-811.

Bergstrom, K., Sham, H.P., Zarepour, M., Vallance, B.A. 2012. Innate host responses to enteric bacterial pathogens: a balancing act between resistance and tolerance. Cellular Microbiology 14(4): 475-84.

Dupaul-Chicoine, J., Yeretssian, G., Doiron, K., Bergstrom, K., McIntire, C.R., LeBlanc P.M., Meunier, C., Turbide, C., Gros, P., Beauchemin, N., Vallance, B.A., and Saleh, M.  2010. Control of intestinal homeostasis, colitis and colitis-associated colorectal cancer by the inflammatory caspases.  Immunity 32(3): 367-78.

Gibson, D.L., Montero, M., Ropeleski, M.J., Bergstrom, K., Merkens, H., Mansson, L.M., Sham, H.P., Ma, C., Huang, J.T., McNagny K.M., and Vallance, B.A. 2010. IL-11 attenuates a TLR4-driven colitis in TLR2 deficient mice by restoring impaired intestinal epithelial STAT3 signaling. Gastroenterology 139(4):1277-88.