Position Title

Professor

Biography

Jeffrey H. Withey, Ph.D., is a Professor in the Department of Biochemistry, Microbiology and Immunology. Dr. Withey earned his Ph.D. in Cellular and Molecular Biology at the University of Michigan in 2000 in the lab of Dr. David Friedman. His postdoctoral studies in bacterial pathogenesis were in the laboratory of Dr. Victor DiRita at the University of Michigan. Dr. Withey joined our faculty in 2006.

Dr. Withey is a two-time Fulbright Scholar, conducting research with collaborators at the National Institute of Cholera and Enteric Diseases (NICED) in Kolkata, India in 2014-2015 and again in 2023-2024. In 2020 he was named a Fulbright Scholar Alumni Ambassador, serving a two year term to advocate for Fulbright programs around the US. He is currently an Academic Editor for PLoS Neglected Tropical Diseases and Associate Editor for Frontiers in Microbiology and is on the editorial boards of Journal of Bacteriology, Journal of Microbiological Methods, and Current Clinical Microbiology Reports.

Education

Ph.D. in Cellular and Molecular Biology from the University of Michigan
B.A. in Biology from Johns Hopkins University

Graduate

Accepting new MS students in 2024: Yes
Accepting new PhD students in 2024: Yes

Office Location

7253 Scott Hall

Research

Dr. Withey's laboratory studies bacterial pathogenesis with an emphasis on host-pathogen interactions, environmental reservoirs and transmission, and the regulation of virulence gene expression.

Research Focus

The Withey lab is interested in enteric pathogens, how they cause diseases in humans, and their aquatic environmental reservoirs. Our primary focus is Vibrio cholerae, the causative agent of the severe diarrheal disease cholera. V. cholerae is an aquatic bacterium that causes disease when ingested by humans in contaminated water. After ingestion, V. cholerae alters its gene expression to produce virulence factors that result in disease. The two major virulence factors of V. cholerae in humans are the cholera toxin (CT) and the toxin co-regulated pilus (TCP). A complex network of transcription regulators controls expression of the genes involved in virulence, including those that encode CT and TCP, together with a collection of other genes whose exact roles in pathogenesis are unclear. The direct transcriptional activator of the majority of these virulence genes is ToxT protein, which is a member of the large AraC/XylS family of transcription regulators. An ongoing goal of the lab is to understand mechanistically how ToxT controls virulence gene expression in the human small intestine, leading to cholera.

The current major research focus of the lab uses zebrafish as a natural animal model for V. cholerae. V. cholerae has been found in the intestines of numerous wild fish species and we developed the zebrafish model to better understand how V. cholerae interacts with hosts in the aquatic environment. V. cholerae colonizes the zebrafish intestinal tract simply by exposure in water, resulting in robust bacterial replication and leading to diarrhea in the fish. Infected fish can then transmit the disease to naïve fish via excreted V. cholerae. Thus, this model in a natural V. cholerae host recapitulates the infectious cycle in humans. Current work includes: 1) identifying factors required for V. cholerae to colonize and survive in the fish, 2) determining how V. cholerae successfully competes for colonization with the abundant zebrafish intestinal microbiota, 3) investigating how bacterial and host gene expression patterns change during colonization and then escape from the host, and 4) assessing the zebrafish immune response to V. cholerae infection.

Publications

• Walton, M.G., Cubillejo, I., Nag, D., and *Withey, J.H. “Advances in cholera research: From molecular biology to public health initiatives.” Frontiers in Microbiology 14:1383 https://doi.org/10.3389/fmicb.2023.1178538 (2023)
• Nag, D., Farr, D.A., Raychaudhuri, S., and *Withey, J.H. “A novel zebrafish model for adherent-invasive Escherichia coli indicates protection from infection by treatment with probiotic E. coli Nissle.” iScience http:// doi.org/10.1016/j.isci.2022.104572 (2022)
• Farr, D.A., Nag, D., Chazin, W.J., Harrison, S., Thummel, R., Luo, X., Raychaudhuri, S., and *Withey, J.H. “Neutrophil-associated responses to Vibrio cholerae infection in a natural host model.” Infection and Immunity https://doi.org/10.1128/iai.00466-21 (2022)
• Farr, D.A., Nag, D., and *Withey, J.H. “Characterization of the immune response to Vibrio cholerae infection in a natural host model.” Frontiers in Cellular and Infection Microbiology https://doi.org/10.3389/fcimb.2021.722520 (2021)
• Stone, J.B., and *Withey, J.H. “H-NS and ToxT inversely control cholera toxin production by binding to partially overlapping DNA sequences.” Journal of Bacteriology https://doi.ord/10.1128/JB.00187-21 (2021)
• Breen, P., Winter, A.D., Theis, K.R., and *Withey, J.H. “Vibrio cholerae induces strain specific modulation of the zebrafish intestinal microbiome.” Infection and Immunity https://doi.org/10.1128/IAI.00157-21 (2021)
• Breen, P., Winter, A.D., Theis, K.R., and *Withey, J.H. “The Vibrio cholerae T6SS is dispensable for colonization but impacts pathogenesis and composition of the zebrafish intestinal microbiome.” Infection and Immunity https://doi.org/10.1128/IAI00151-21 (2021)
• Nag, D., Farr, D., Walton, M.G., and *Withey, J.H. “Zebrafish models for pathogenic Vibrios.” Journal of Bacteriology 202(24) DOI: 10.1128/JB.00165-20 (2020)
• Nag, D., Breen, P., Raychoudhuri, S., and Withey, J.H. “Glucose metabolism by E. coli inhibits Vibrio cholerae intestinal colonization of zebrafish.” Infection and Immunity, DOI: 10.1128/IAI.00486-18 (2018)
• Nag, D., Mitchell, K.C., Breen, P., and Withey, J.H. “Assessing V. cholerae colonization and pathogenesis in the adult zebrafish model.” Journal of Visualized Experiments, 137: doi: 10.3791/57767 (2018)
• Mitchell, K.C., Breen, P., Britton, S., Neely, M.N., and Withey, J.H. “Quantifying Vibrio cholerae Enterotoxicity in a Zebrafish Infection Model.” Applied and Environmental Microbiology, 83(16):e00783-17. (2017)
• Withey, J.H., Nag, D., Plecha, S.C., Sinha, R., and Koley, H. “Conjugated linoleic acid reduces cholera toxin production in vitro and in vivo by inhibiting Vibrio cholerae ToxT activity,” Antimicrobial Agents And Chemotherapy, 59(12):7471-7576 (2015)
• Plecha, S.C., and Withey, J.H. “The mechanism for inhibition of Vibrio cholerae ToxT activity by the unsaturated fatty acid components of bile.” Journal of Bacteriology, 197(10):1716-1725 (2015)
• Thomson, J.J., Plecha, S.C., and Withey, J.H. “A small unstructured region in Vibrio cholerae ToxT mediates the response to positive and negative effectors and ToxT proteolysis.” Journal of Bacteriology 197(3):654-668 (2015)
• Thomson, J.J., and Withey, J.H. “Bicarbonate increases binding affinity of Vibrio cholerae ToxT to virulence gene promoters.” Journal of Bacteriology, 196(22):3872-3880 (2014)
• Runft, D., Mitchell, K.C., Abuaita, B.H., Allen, J., Bajer, S., Ginsberg, K, Neely, M.N., and Withey, J.H. “Zebrafish as a Natural Host Model for Vibrio cholerae Colonization and Transmission.” Applied and Environmental Microbiology, 80(5):1710-1717. (2014)

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