Joseph P. Zackular, Ph.D.

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Assistant Professor of Pathology and Laboratory Medicine
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
1211A Abramson Research Center
3615 Civic Center Blvd
Philadelphia, PA 19104
Office: 2674265016
B.S. (Microbiology)
University of Massachusetts - Amherst, 2008.
M.S. (Microbiology)
University of Massachusetts - Amherst, 2009.
Ph.D. (Microbiology & Immunology)
University of Michigan, 2014.
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Description of Research Expertise

The overall goal of the Zackular laboratory is to understand how interactions between the host, gut microbiota, and pathogenic microbes impact human health and disease. At the center of our research is the important nosocomial pathogen, Clostridium difficile. Over the past decade, incidence, severity, and costs associated with C. difficile infection (CDI) have increased dramatically. The primary risk factor for CDI is antibiotic treatment, which disrupts the resident gut microbiota and leads to susceptibility to C. difficile. Interestingly, non-antibiotic associated CDI cases are on the rise, suggesting that unexplored host, environmental, and microbiota factors likely influence CDI. We are interested in identifying these environmental factors and defining underlying mechanisms of microbiota disruption and modulation of disease.

The research in our laboratory draws from numerous fields including microbiology, immunology, microbial ecology, host-pathogen interactions, and microbiota research. Our strategy is to leverage the strengths of high throughput sequencing technologies with more mechanistic strategies involving bacterial genetics, mass spectrometry, and imaging. Trainees in the laboratory gain interdisciplinary training and are involved in translational studies at the interface of basic and clinical research.

Keywords: Clostridium difficile; Enterococcus; Gut microbiome; Host-pathogen interactions; Pathogen-microbiota interactions; Inflammatory Bowel Disease; Colorectal cancer.

Selected Publications

Soto Ocaña J., Bayard N.U., Hart J.L., Thomas A., Furth E.E., Lacy D.B., Aronoff D.M., Zackular J.P. : Nonsteroidal anti-inflammatory drugs sensitize epithelial cells to Clostridioides difficile toxin-mediated mitochondrial damage. Science Advances 2023 Notes: In press.

Specker J.T., Smith A.B., Zackular J.P., and Prentice B.M.. : Investigation of Microbial Cooperation via Imaging Mass Spectrometry Analysis of Bacterial Colonies Grown on Agar and in Tissue During Infection. Journal of Visualized Experiments 18(189): e64200, Nov 2022.

Smith A.B., Jenior M.L., Keenan O., Hart J.L., Specker J, Abbas A, Rangel P.C., Di C., Green J., Bustin K. A., Gaddy J.A., Nicholson M.R., Laut C., Kelly B.J., Matthews M.L, Evans D.L., Van Tyne D., Furth E.E., Papin J.A., Bushman F.D., Erlichman J., Baldassano R.N., Silverman M.A., Dunny G.M., Prentice B.M., Skaar E.P., and Zackular J.P. : Enterococci enhance Clostridioides difficile pathogenesis. Nature 611(7937): 780-786, Nov 2022.

Bushman FD, Conrad M, Ren Y, Zhao C, Gu C, Petucci C, Kim MS, Abbas A, Downes KJ, Devas N, Mattei LM, Breton J, Kelsen J, Marakos S, Galgano A, Kachelries K, Erlichman J, Hart JL, Moraskie M, Kim D, Zhang H, Hofstaedter CE, Wu GD, Lewis JD, Zackular JP, Li H, Bittinger K, Baldassano R.: Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease. Cell Host Microbe 28: 422-433, Sep 2020.

Abbas A. and Zackular J.P. : Microbe-microbe Interactions During Clostridioides difficile Infection. Current Opinions in Microbiology 53: 19–25, February 2020.

Smith A.B., Soto Ocana J., and Zackular J.P.: From Nursery to Nursing House: Emerging Concepts in Clostridioides difficile Pathogenesis. Infection and Immunity 88(7): e00934-19, June 2020.

Zackular J.P., Kirk Leslie, Trindade B.C., Skaar E.P., and Aronoff D.M.: Misoprostol protects mice against severe Clostridium difficile infection and promotes recovery of the gut microbiota after antibiotic perturbation. Anaerobe 58: 89-94, June 2019.

Maseda D.*, Zackular J.P.*, Trindade B., Kirk L., Crofford L.J., Schloss P.D., Roxas J.L., Viswanathan V.K., Vedantam G., Rogers L.M., Washington M.K., Skaar E.P., and Aronoff D.M. : Nonsteroidal anti-inflammatory drugs alter the microbiota and exacerbate Clostridium difficile colitis while dysregulating the inflammatory response. MBio 10(1): e02282-18, 2019 Notes: *These authors contributed equally.

Knippel R.J., Zackular J.P., Moore J.L., Celis A.I., Weiss A., Washington M.K., DuBois J.L., Caprioli R.M., and Skaar E.P. : Heme sensing and detoxification by HatRT contributes to pathogenesis during C. difficile infection. PLoS Pathogens 14(12): e1007486, 2018.

Zackular J.P., Moore J.L., Jordan A.T., Juttukonda L.J., Noto M.J., Nicholson M.R., Crews J.D., Semler M.W., Zhang Y., Ware L.B., Washington M.K., Chazin W.J., Caprioli R.M., Skaar E.P.: Dietary Zinc Alters the Microbiota and Decreases Resistance to Clostridium Difficile Infection Nature Medicine 22(11): 1330-34, 2016.

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Last updated: 10/31/2023
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