Joseph P. Zackular, PhD

Assistant Professor of Pathology and Laboratory Medicine
Assistant Professor of Microbiology
Perelman School of Medicine at the University of Pennsylvania

Contact Information1211A Abramson Research Center
3615 Civic Center Blvd
Philadelphia, PA, 19104
Office: 267-426-5016


Specialty Division

Cancer and Immunobiology

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.


B.S. (Microbiology), University of Massachusetts - Amherst, 2008
M.S. (Microbiology), University of Massachusetts - Amherst, 2009
Ph.D. (Microbiology & Immunology), University of Michigan, 2014

Specialty Certification

Postgraduate Training

Postdoctoral Research Fellow, Vanderbilt University Medical Center, Nashville, TN, 2014-2018

Awards and Honors

Selected for ASM Live Research Highlight, May 2013, 2013
Vanderbilt Training Grant in Gastroenterology (NIH/NIDDK), 2014
Top Abstract Award, Vanderbilt Postdoctoral Association and
Shared Resources Symposium, 2015
Top Oral Presentation Award, 59th Annual Wind River Conference on
Prokaryotic Biology, 2015
Wind River Conference on Prokaryotic Biology Travel Award, 2015
Top Abstract Award, 2015 Vanderbilt Institute of Chemical Biology Annual
Symposium, 2015
Ward J. MacNeal Educational and Scientific Memorial Trust Distinguished
Dissertation Award, Department of Microbiology & Immunology, University
of Michigan, 2015
F32 Ruth L. Kirschstein National Research Service Award Individual
Postdoctoral Fellowship (NIH/NIAID), 2015
Best Poster Award, Microbiology and Immunology Division,
Vanderbilt Postdoctoral Association and Shared Resources Symposium, 2016
Top Poster Award, 2016 Vanderbilt Digestive Disease Research Center
Annual Symposium, 2016
Sidney P. Colowick Award for Outstanding Postdoctoral Research, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center., 2017
Best Poster Award, Immunology and Infection Division,
Vanderbilt Postdoctoral Association and Shared Resources Symposium., 2017
K22 Career Transition Award (NIH/NIAID), 2019
NIH Loan Repayment Program Award (NIH/NIAID), 2019
R13 NIH Early Career Scientist Travel Grant Awardee (NIH), Clostpath 11, 2019
2020 Award for Excellence in Mentoring Research Trainees, Children's Hospital of Philadelphia, 2020
NIH Loan Repayment Program Competing Renewal Awardee (NIH/LRP/NIAID), 2022
Klaus Hummeler High-Impact Publication Award, Children’s Hospital of Philadelphia, 2023
Heritage Lectureship - Department of Microbiology, University of Michigan, 2024

Memberships and Professional Organizations

American Society for Microbiology, 2008 - Present
Anaerobe Society of the Americas, 2015 - Present
Eastern Pennsylvania American Society for Microbiology Chapter, 2018 - 2021
National Mouse Metabolic Phenotyping Center MICROMouse Program, 2018 - 2018
American Gastroenterology Association, 2020 - 2022
Study Section (NIH) Antibacterial Drug Discovery or Resistance (DDR), 2021 - Present
Center for Molecular Studies in Digestive and Liver Diseases, 2021 - Present
American Gastroenterological Association, 2022 - 2022
Wellcome Trust, 2023 - 2023
European Society of Clinical Microbiology and Infectious Diseases (ESCMID), 2023 - Present
American Gastroenterological Association, 2023 - 2023
Food and Drug Administration - Laboratory of Mucosal Pathogens and Cellular Immunity, 2024 - 2024

Web Links

Selected Publications

Liberation of host heme by Clostridioides difficile-mediated damage enhances Enterococcus faecalis fitness during infection

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., mBio 15(1): e0165623, 2024, PMID:38078767

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Nonsteroidal anti-inflammatory drugs sensitize epithelial cells to Clostridioides difficile toxin-mediated mitochondrial damage.

Soto Ocaña J., Bayard N.U., Hart J.L., Thomas A., Furth E.E., Lacy D.B., Aronoff D.M., Zackular J.P., Science Advances 9(29): eadh5552, 2023, PMID:37467340

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Investigation of Microbial Cooperation via Imaging Mass Spectrometry Analysis of Bacterial Colonies Grown on Agar and in Tissue During Infection

Specker J.T., Smith A.B., Zackular J.P., and Prentice B.M.., Journal of Visualized Experiments 18(189): e64200, 2022, PMID:36468707

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Enterococci enhance Clostridioides difficile pathogenesis

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., Nature 611(7937): 780-786, 2022, PMID:36385534

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Multi-omic Analysis of the Interaction between Clostridioides difficile Infection and Pediatric Inflammatory Bowel Disease

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., Cell Host & Microbe 28(): 422-433, 2020, PMID:32822584

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Microbe-microbe Interactions During Clostridioides difficile Infection

Abbas A. and Zackular J.P., Current Opinions in Microbiology 53(): 19–25, 2020, PMID:32088581

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From Nursery to Nursing House: Emerging Concepts in Clostridioides difficile Pathogenesis.

Smith A.B., Soto Ocana J., and Zackular J.P., Infection and Immunity 88(7): e00934-19, 2020, PMID:32122939

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Misoprostol protects mice against severe Clostridium difficile infection and promotes recovery of the gut microbiota after antibiotic perturbation

Zackular J.P., Kirk Leslie, Trindade B.C., Skaar E.P., and Aronoff D.M., Anaerobe 58(): 89-94, 2019, PMID:31220605

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Nonsteroidal anti-inflammatory drugs alter the microbiota and exacerbate Clostridium difficile colitis while dysregulating the inflammatory response.

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., MBio 10(1): e02282-18, 2019, PMID:30622186

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Dietary Zinc Alters the Microbiota and Decreases Resistance to Clostridium Difficile Infection

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., Nature Medicine 22(11): 1330-34, 2016, PMID:27668938

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