Professor

Medicine Department, School of Medicine
Director, Bloomberg-Kimmel Institute Microbiome Program
Director, Johns Hopkins Germ-free Murine Facility
Co-Director, Microbiome Forum

RESEARCH OVERVIEW

My laboratory focuses on studies to determine how the microbiota contributes to colorectal cancer and immunotherapy. We have studied in detail the carcinogenic bacterium, enterotoxigenic Bacteroides fragilis (ETBF), using this organism as a model for inducing colon inflammation and carcinogenesis and, more recently, mechanisms by which ETBF interact with host gene mutations, impacting immunotherapy outcomes. In addition, we study the pro-carcinogenic bacteria, colibactin-producing Escherichia coli, Fusobacterium spp and, most recently, Clostridioides difficile. Our data were the first to report a Th17 mechanism for inflammation-induced endogenous colon tumor induction; subsequent work by other groups has confirmed the importance of Th17/IL-17 mechanisms in many cancers including human colon cancer. We also study the importance of bacterial communities in the pathogenesis of colon cancer and immunotherapy with an increasing interest in metabolites influencing host:microbial interactions. The laboratory employs a wide range of methods to achieve our experimental goals including next generation sequencing, RNAseq, microbiology, mouse models, and metabolomics among others. Our long-term goal is to devise ways to utilize the microbiota markers to identify and better predict those at risk for colon carcinogenesis and to more effectively treat cancer patients. 

Cancer Biology | Immunology and Infectious Diseases | Translational Research

Selected Publications

Queen J, Shaikh F, Sears CL. Understanding the mechanisms and translational implications of the microbiome for cancer therapy innovation. Nature Cancer, 2023

Drewes JL, Chen J, Markham NO, Knippel RJ, Domingue JC, Tam AJ, Chan JL, Kim L, McMann M, Stevens C, Dejea CM, Tomkovich S, Michel J, White JR, Mohammad F, Campodónico VL, Heiser CN, Wu X, Wu S, Ding H, Simner P, Carroll K, Shrubsole MJ, Anders RA, Walk ST, Jobin C, Wan F, Coffey RJ, Housseau F, Lau KS, Sears CL. Human Colon Cancer-Derived Clostridioides difficile Strains Drive Colonic Tumorigenesis in Mice. Cancer Discovery, 2022.

DeStefano Shields CE, White JR, Chung L, Wenzel A, Hicks JL, Tam AJ, Chan JL, Dejea CM, Fan H, Michel J, Maiuri AR, Sriramkumar S, Podicheti R, Rusch DB, Wang H, De Marzo AM, Besharati S, Anders RA, Baylin SB, O'Hagan HM, Housseau F, Sears CL. Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy. Cancer Discovery, 2021.

Shaikh FY, Gills JJ, Mohammad F, White JR, Stevens CM, Ding H, Fu J, Tam A, Blosser RL, Domingue JC, Larman TC, Chaft JE, Spicer JD, Reuss JE, Naidoo J, Forde PM, Ganguly S, Housseau F, Pardoll DM, Sears CL. Murine fecal microbiota transfer models selectively colonize human microbes and reveal transcriptional programs associated with response to neoadjuvant checkpoint inhibitors. .

Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, Housseau F, Pardoll DM, Sears CL. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nature Medicine, 2009.

Learn More

NCBI Bibliography | Faculty Profile | Lab Website | LinkedIn