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 were in the laboratory of Dr. Victor DiRita at the University of Michigan. Dr. Withey joined our faculty in 2006.
Dr. Withey has worked at the National Institute for Cholera and Enteric Diseases (NICED) in Kolkata, India as part of his effort to develop a zebrafish model for cholera. He was named a Fulbright-Nehru Senior Scholar in 2014-2015 and spent 5 months conducting research in Kolkata. In addition, he is on the editorial boards of Infection and Immunity, Journal of Bacteriology, Journal of Microbiological Methods, and Current Clinical Microbiology Reports.
Ph.D. in Cellular and Molecular Biology from the University of Michigan
Accepting new MS students in 2020/21?: Yes
Accepting new PhD students in 2020/21?: Yes
Office Location7253 Scott Hall
Dr. Withey's laboratory studies bacterial pathogenesis with an emphasis on the regulation of virulence gene expression and host-pathogen interactions.
Our current model system 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. A major focus of the lab in the past several years has been the identification of in vivo signals that control virulence gene expression by affecting ToxT activity. Now that some of these signals have been identified, we are determining the precise mechanisms by which they alter gene expression, resulting in human disease.
Another major research focus is the development of zebrafish as a natural animal model for V. cholerae. In collaboration with Dr. Melody Neely, we successfully established the viability of this model. V. cholerae colonize the zebrafish intestinal tract simply by exposure in water, resulting in diarrhea and signs of pathogenesis in the fish. Infected fish can then transmit the disease to naïve fish. Thus this model in a natural V. cholerae host recapitulates the infectious cycle in humans. Current work includes: 1) identifying factors that are required for V. cholerae to colonize and survive in the fish, 2) determining how V. cholerae can compete with the abundant intestinal microbiota to establish a niche, 3) investigating how gene expression patterns change during colonization and escape from the host, and 4) assessing the zebrafish immune response to V. cholerae infection.
- Breen, P., Winters, A.D., Theis, K.R., and Withey, J.H. “Internal versus external pressures: Effect of housing systems on zebrafish and tank water microbiomes.” Zebrafish, DOI:10.1089/zeb.2018.1711 (2019)
- Hounmanou, Y.M.G., Mdegela, R.H., Dougnon, T.V., Madsen, H., Withey, J.H., Olsen, J.E., and Dalsgaard, A. “Tilapia (Oreochromis niloticus) as a reservoir host for survival and transmission of Vibrio cholerae O1 biotype El Tor in the aquatic environment” Accepted, Frontiers in Microbiology (2019)
- 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)
- Howlader, D.R., Sinha, R., Nag, D., Majumder, N., Mukherjee, P., Bhaumik, U., Withey, J.H., and Koley, H. “Zebrafish as a novel model for Non-Typhoidal Salmonella pathogenesis, transmission and vaccine efficacy.” Vaccine, 34:5099-5106 (2016)
- 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)