PEOPLE

Joseph P. Zackular, Ph.D.

Assistant Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania
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: 2674265016

Email: joseph.zackular@pennmedicine.upenn.edu

Specialty Division

Immunobiology and Experimental Pathology

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.

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Rotation projects:

The impact of environmental factors on the gut microbiota and C. difficile infection:

There is growing evidence that environmental factors, such as diet, have a profound impact on the structure and function of the gut microbiota. With the rise of non-antibiotic associated CDI, we are interested in studying the potential impact of environmental factors on susceptibility to and severity of C. difficile. Of particular interest are non-steroidal anti-inflammatory drugs (NSAIDs), which are the most widely consumed pharmaceutical drugs world wide. Epidemiological data and our preliminary work suggest that NSAIDs may alter the gut microbiota and impact severity of CDI.

Pathogen-microbiota interactions during Clostridium difficile infection:

Antibiotic treatment can have a profound impact on the structure and function of the gut microbiota, leading to a loss in colonization resistance to invading pathogens, such as C. difficile. However, the gut is not sterile following antibiotic treatment and pathogens like C. difficile are entering a polymicrobial environment upon colonization. Antibiotic resistant members of the microbiota, such as the Enterococci, frequently thrive following antibiotic treatment and can become highly abundant during CDI. We are interested in studying how members of the gut microbiota that remain after antibiotic treatment impact C. difficile during infection. Interspecies interactions can be attributed to the development of numerous polymicrobial infections and bacterial synergy is associated with disease exacerbation and increased antimicrobial resistance.

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

Education

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

Deans Honors List, University of Massachusetts, 2004-2008
Graduation with Honors, University of Massachusetts, 2008
Rackham Graduate School Travel Grant Award, 2012
Rackham Graduate Student Research Grant, 2012
Rackham Graduate School Travel Grant Award, 2013
Selected for ASM Live Research Highlight, May 2013, 2013
Vanderbilt Training Grant in Gastroenterology (NIH/NIDDK), 2014
Top Abstract Award, 2015 Vanderbilt Institute of Chemical Biology Annual
Symposium, 2015
Top Abstract Award, Vanderbilt Postdoctoral Association and
Shared Resources 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
Top Oral Presentation Award, 59th Annual Wind River Conference on
Prokaryotic Biology, 2015
Wind River Conference on Prokaryotic Biology Travel Award, 2015
Top Poster Award, 2016 Vanderbilt Digestive Disease Research Center
Annual Symposium, 2016
Best Poster Award, Microbiology and Immunology Division,
Vanderbilt Postdoctoral Association and Shared Resources 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
Selected as Postdoc Invited Speaker for Outstanding Research
Accomplishments, Annual Infection and Immunity Symposium, Vanderbilt
University Medical Center, 2017
K22 Career Transition Award, NIH/NIAID, 2019

Memberships and Professional Organizations

American Society for Microbiology, 2008 - Present
Anaerobe Society of the Americas, 2015 - Present
National Mouse Metabolic Phenotyping Center MICROMouse Program, 2018 - 2018
American Society for Microbiology, 2019 - 2019

Web Links


Selected Publications

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

Heme sensing and detoxification by HatRT contributes to pathogenesis during C. difficile infection.

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., PLoS Pathogens 14(12): e1007486, 2018

The Role of Zinc and Nutritional Immunity in Clostridium Difficile Infection.

Zackular J.P. and Skaar E.P., Gut Microbes 9(5): 469-76. , 2018, PMID:29533126

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Dietary manganese promotes staphylococcal infection of the heart

Juttukonda L.J., Berends E.T.M, Zackular J.P., Stier M.T., Moore J.L., Zhang Y, Schmitz J.E., Beavers W.N., Wijers C.D., Kehl-Fie T, Atkinson J, Peebels R.S., Torres V.J., Caprioli R.M.,Skaar E.P., Cell Host and Microbe 22(): 1-12, 2017

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

Manipulation of the Gut Microbiome Reveals Role for in Colorectal Cancer

Zackular J.P., Baxter N.T., Chen G.Y., Schloss P.D., mSphere 1(1): e00001-15, 2015

The Human Gut Microbiome as a Screening Tool for Colorectal Cancer

Zackular J.P., Rogers M.A., Ruffin M.T., Schloss P.D., Cancer Prevention Research 7(11): 1112–21, 2014

Zackular J.P., Chazin W.J.,Skaar E.P.

Nutritional Immunity: S100 Proteins at the Host-Pathogen Interface, Journal of Biological Chemistry, 2015

The Gut Microbiome Modulates Colon Tumorigenesis.

Zackular J.P., Baxter N.T., Iverson K.D., Sadler W.D., Petrosino J.F., Chen G.Y., and Schloss P.D., MBio 4(5): e00692-13, 2013

Structure of the Gut Microbiome Following Colonization with Human Feces Determines Colonic Tumor Burden

Baxter N.T.*, Zackular J.P.*, Iverson K.D., Chen G.Y., and Schloss P.D., Microbiome 2(20): , 2014

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