Joseph P. Zackular, Ph.D.

faculty photo
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 Zackular laboratory is focused on understanding how interactions between the host, gut microbiota, and pathogens impact human health and disease. The labs efforts primarily center on the nosocomial pathogen, Clostridioides difficile, which is an urgent global public health threat. The Zackular lab is interested in understanding how the gut microbiota shapes C. difficile fitness and virulence, and the team is studying how this complex microbial community alters host responses to infection. Recent work from the Zackular lab has focused on elucidating cooperative interactions between C. difficile and other pathogens, such as the enterococci. Leveraging knowledge learned from studying polymicrobial interactions and microbial ecology during infection, the Zackular lab is also developing novel vaccine strategies for the prevention of C. difficile infection and using microbiome-based therapies for the treatment of disease.

Dr. Zackular is co-director of the Center for Microbial Medicine at the Children’s Hospital of Philadelphia, which focuses on i.) bringing microbiome-based medicine to pediatric patients and ii) using whole genome sequencing of pathogens to provide children with improved and personalized treatments for infections.

Selected Publications

Smith A.B., Specker J.T., Hewlett K.K., Scoggins T.R., Knight M., Lustig A.M., Lid Y., Evans K.M., Guob Y., She Q., Christopher M.W., Garrett T.J., Moustafa A.M., Van Tyne D., Prentice B.M., Zackular J.P.: Liberation of host heme by Clostridioides difficile-mediated damage enhances Enterococcus faecalis fitness during infection. mBio 15(1): e0165623, January 2024.

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 9(29): eadh5552, July 2023.

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 Notes: Highlighted in Microcosm (https://asm.org/magazine/2023/spring/friends-foes-microbial-interactions-infections), Highlighted in Nature Reviews Microbiology (https://www.nature.com/articles/s41579-022-00838-2). Awarded the Dr. Klaus Hummeler High-Impact Publication Award at CHOP.

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 Notes: Played important role in large collaborative program. I was leader in analysis and interpretation, and led mechanistic work that was central to the paper. Middle authorship on this manuscript is not fully representative of my impact on this work.

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.

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: 05/22/2024
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