Christine McDonald, PhD
Associate Staff
Associate Professor of Molecular Medicine at Case Western Reserve University
Institutional Biosafety Chair
Email: [email protected]
Location: Cleveland Clinic Main Campus
Research
Microplastics & Inflammatory Bowel Disease: Inflammatory bowel disease is a complex disease with many factors combining to determine who develops this life-long autoinflammatory disease. Environmental factors are thought to be important disease triggers for individuals with family risk factors. Microplastics are emerging as potential contributors to the development or exacerbation of inflammatory bowel disease; however, which microplastics and how microplastics trigger intestinal inflammation is not well understood. Our goal is to fill this gap in understanding and determine the mechanisms underlying microplastic acceleration of disease using a combination of environmental and clinical samples with pre-clinical models and in vitro experimental systems.
Anti-bacterial Defenses in Health & Disease: Our research team investigates how we defend ourselves against bacterial infection. Alterations to these defenses are thought to be involved in the development of auto-inflammatory diseases, such as Crohn's disease, as well as involved in cancer development. We are attempting to understand how changes in anti-bacterial defenses drive disease in the gut, skin, and lung. Through this we we also aim to define the protective immune defenses of the intestine to shape future therapeutic approaches to diarrheal disease. Some of the same anti-microbial defenses found in the gut also act in the skin. We are exploring whether drugs that increase these natural defenses of the skin can be used to treat infections with antibiotic-resistant bacteria or halt the development of skin cancer.
Biography
Dr. Christine McDonald is an Associate Staff member in the Department of Inflammation & Immunity of Cleveland Clinic Research and an Associate Professor of Molecular Medicine in the Cleveland Clinic Lerner College of Medicine. She also serves as Chair of the Institutional Biosafety Committees of the Cleveland Clinic.
Dr. McDonald heads a research team that investigates microbial sensor signaling and control of anti-microbial defenses, with an emphasis on the protective role of NOD2 in bacterial infections of the skin and gut, as well as the pathogenic role of NOD2 dysregulation in inflammatory diseases. Additional areas of research include mechanistic approaches to cancer therapy, biomaterials for treatment of antibiotic-resistant bacterial infections, and the influence of environmental factors, such as microplastics and diet, in chronic disease. This research is supported by grants from the Department of Defense, the National Institutes of Health, and philanthropic donations.
Dr. McDonald has received several awards from the Cleveland Clinic, including the Excellence in Service Award, the Excellence in Mentoring Award, and the LRI Innovator Award. She is also an American Gastroenterology Association Fellow.
Dr. McDonald earned her PhD in Cellular & Molecular Immunology & Pathology from the State University of New York at Stony Brook under the mentorship of Dr. Nancy C. Reich-Marshall. She obtained additional training as a postdoctoral fellow at the University of Michigan in bacterial pathogenesis in the laboratory of Jack E. Dixon, PhD and continued her postdoctoral fellowship training in innate immunity under the mentorship of Gabriel Nunez, MD.
Education & Professional Highlights
Postdoctoral Fellowship - University of Michigan Medical School Laboratory of Gabriel Nunez, MD 2003-2006
Postdoctoral Fellowship - University of Michigan Laboratory of Jack E. Dixon, PhD, 2001-2003
Graduate Education - State University of New York at Stony Brook PhD in Molecular & Cellular Immunology & Pathology, Laboratory of Nancy C. Reich-Marshall, PhD 2001
Undergraduate Education - Macalester College BA in Biology 1992
"CIMER Trained Mentor" indicates the principal investigator has completed mentorship training based on curriculum from the Center for the Improvement of Mentored Experiences in Research, aimed at advancing mentoring relationships and promoting cultural change in research.
Research
Microplastics & IBD
Our research investigates the control of immune responses and how alterations in these responses contribute to the development of the chronic and debilitating inflammatory bowel disease, Crohn’s disease (CD). Crohn’s disease (CD) is complex with multiple risk factors combining to determine who will develop the disease. No single risk factor is enough to cause CD. What we don’t currently understand is how the combination of these factors multiply the risk of developing CD. Family history (genetics) is clearly linked to increased disease risk, but this is something that we cannot change. A different risk factor is microplastic particle exposure, which increasing data shows to impair intestinal barrier defenses and induce inflammation. Research in the McDonald lab is examining the effect of microplastics on the development of intestinal inflammation and probing the underlying mechanisms that drive disease pathology. Our research uses sophisticated, multiplexed molecular analyses in pre-clinical models that incorporate genetic disease risk factors, patient-derived cell systems, and CD patient samples.
Anti-Bacterial Defenses of the Intestine & Skin
Another area of research is the development of new antimicrobial treatments for antibiotic-resistant bacteria skin wound infections and intestinal pathogen infections. Antibiotic-resistant bacterial infections are a major problem in healthcare settings because our most powerful drugs to kill these bacteria are becoming ineffective. Therefore, there is an urgent need to develop new, safe and effective treatments. Our research investigates mechanisms to enhance natural innate immune responses to bacteria mediated by the sensor protein, nucleotide-binding, oligomerization domain 2 (NOD2). Our studies show that stimulation of this antimicrobial sensor increases the production and release of natural antibiotic factors from skin and intestinal epithelial cells and increases the potency of bacterial killing by immune cells, rather than targeting bacteria directly. Induction of this multifaceted antimicrobial defense program will target a broad range of bacterial strains, avoid the development of resistant organisms, and could be combined with existing antimicrobial treatments to potentiate a therapeutic response.
Cancer Therapeutics
Our lab has been involved in the development of an ointment from a drug called PALA (N-phosphonacetyl-L-aspartate) that treats, and even helps to prevent, skin cancer. After our lab discovered that PALA activates the immune system, further investigation into the new role of PALA as an immune activator has revealed it to be a pan-cancer agent with in vitro and in vivo success in treating preclinical models of lung, breast, and skin cancer, with potential to treat many other forms of cancer. We are collaborating with other labs to further understand PALA’s mechanisms of action and demonstrate its pan-cancer potential. In collaboration with the lab of Dr. George Stark, we have launched PALA Pharmaceuticals, Inc. to translate our research findings into the clinic.
Our Team
Selected Publications
Peer Reviewed Publications:
Naydenov N.G., Zafar A., Lechuga S., Marino-Melendez A., Hammer J.A., Fowler V.M., McDonald C., Campellone K., & Ivanov A.I. (2026) Myosin IIA motor regulates attaching-effacing bacteria interactions with intestinal epithelium. Gut Microbes,18:1, 2638002, doi: 10.1080/19490976.2026.2638002. PMCID: PMC12959189.
Kongai T., Johnson E.E., Ponti A.K., Shanteau-Jackson M., West G.A., Dombrovski T., McDonald C.*, LaFramboise T.* (2026) Overexpression of LINC01605 promotes early tumorigenic phenotypes in primary human colon organoids. Genes & Diseases, https://doi.org/10.1016/ j.gendis.2026.102125. *co-corresponding authors
Shrestha D., Pant B.D., Roychowdhury S., Gandhirajan A., Cross E., Chhabria M., Bauer S.R., Jeng M., Mitchell M., Mehkri O., Zaidi F., Ahuja A., Wang X., Wang Y., McDonald C., Longworth M.S., Stappenbeck T.S., Stark G.R., Scheraga R.G., Vahharajani V. (2025) Immunometabolic chaos in septic shock. Journal of Leukocyte Biology, 117(2)qiae211. doi: 10.1093/jleuko/qiae211. PMCID: PMC11879763.
Bhatt H.*, Flatley E.*, Cooper K.D., Jorgensen T.N., McDonald C., Fernandez A.P. (2024) Control of dermatomyositis skin disease activity lags behind control of muscle disease activity during the early treatment stages of classic dermatomyositis: a retrospective, single-centre study. Skin Health and Disease, 4(3):e357. doi.org/10.1002/ski2.357. PMCID: PMC11150736. *co-first authors
Jatana S.*, Ponti A.K., Johnson E.E., Rebert N.A., Smith J.L., Fulmer C.G., Maytin E.V., Achkar J.-P., Fernandez A.P., & McDonald C*. (2023) A novel murine model of pyoderma gangrenosum reveals that inflammatory skin-gut crosstalk is mediated by IL-1β-primed neutrophils. Frontiers in Immunology, 14:1148893. doi: 10.3389/fimmu.2023.1148893. PMCID: PMC10354730. *co-corresponding authors
Mahen K.K., Markley L., Bogart J., Klataka H., Krishna V., Maytin E.V., Stark G.R. & McDonald C. (2023) Topical N-phosphonacetyl-L-aspartate is a dual action candidate for treating non-melanoma skin cancer. Experimental Dermatology, 32(9):1485-1497. doi: 10.111/exd.14853. PMCID: PMC10527533.
Peters D.E., Norris L.D., Tenora L., Šnajdr I., Ponti A.K., Zhu X., Sakamoto S., Veeravalli V., Pradhan M., Alt J., Thomas A.G., Majer P., Rais R.*, McDonald C.*, & Slusher B.S.* (2023) Discovery of (S)-IBD3540: A gut-restricted glutamate carboxypeptidase II inhibitor reduces monocytic inflammation and improves preclinical colitis. Science Translational Medicine, 15(708):eabn7491. doi: 10.1126/scitranslmed.abn7491. Epub 2023 Aug 9. PMID: 37556558, PMCID: PMC10661206. *co-corresponding authors
Narang J.*, Jatana S.*, Ponti A.K., Musich R., Gallop J., Wei A.H., Seck S., Johnson J., Kokoczka L., Nowacki A.S., McBride J.D., Mireles-Cabodevila E., Gordon S., Cooper K., Fernandez A.P.+, & McDonald C.+ (2023) Abnormal thromobosis and neutrophil activation increase hospital-acquired sacral pressure injuries and morbidity in COVID-19 patients. Frontiers in Immunology, 14:1031336. doi: 10.3389/fimmu.2023.1031336. PCMID: PMC10070761. *co-first authors, +co-corresponding authors
Zangara M.T., Ponti A.K., Miller N.D., Engelhart M.J., Ahern P.P., Sangwan N., & McDonald C. (2022) Maltodextrin alters intestinal epithelial differentiation and proliferation to impair the mucus barrier and accelerates colitis. Frontiers in Immunology, 13:841188. doi: 10.3389/fimmu.2022.841188. PMCID: PMC8963984.
Said S., Jatana S., Ponti A.K., Johnson E.E., Such K.A., Zangara M.T., Madajka M., Papay F., & McDonald C. (2022) Development of a Reproducible Porcine Model of Infected Burn Wounds. Journal of Biological Methods, 9(1):e158. doi: 10.14440/jbm.2022.379. PMCID: PMC9058257.
Hot Off the Press Preprints:
Johnston I., Johnson E.E., Khan A., Longworth M.S. McDonald C. (2026) Epithelial NCAPD3 expression protects against stress-induced intestinal injury in mice. bioRxiv, 2026.04.21.719792; doi: https://doi.org/10.64898/2026.04.21.719792
Khan, A., Ray, G., Musich, R., Selmi, I., Gjojdeshi, A., Talley, M.J., Rayan, C., Fulmer, C., Peterson, J., Bai, I., West, G., Johnson, E., McDonald, C., Rieder, F., & Longworth, M.S. Condensin Upregulation Induces Intestinal Stem Cell Senescence, Driving Cell Death and Increased Intestinal Permeability. Available at SSRN: https://ssrn.com/abstract=6502401 or http://dx.doi.org/10.2139/ssrn.6502401
Ponti A.K., Zangara M.T., O’Connor C.M., Johnson E.E., & McDonald C. (2022) N-phosphonacetyl-L-aspartate enhances type I interferon anti-viral responses through activation of non-canonical NOD2 signaling. bioRxiv, 2022.02.08.479597. doi: https://doi.org/10.1101/2202.02.08.479597.
Careers
Research News
PALA’s fifty-year journey to a promising multi-cancer treatment highlights the importance of basic science in research.
A new class of gut-restricted, oral therapies that target the enzyme glutamate carboxypeptidase II shows promise in treating inflammatory bowel disease (IBD).
The topical ointment uses the small molecule PALA, first developed to treat cancer 50 years ago.
The former chair of the Lerner Research Institute, George Stark, PhD, was celebrated with a day-long cancer symposium with talks from collaborators and colleagues on July 7.
This new discovery shows drug called PALA (N-phosphonacetyl-L-aspartate) promotes the death of antibiotic-resistant bacteria in skin wounds without use of antibiotics.