Associate Professor of Molecular Medicine at Case Western Reserve University
Institutional Biosafety Chair
Location: Cleveland Clinic Main Campus
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 risk factors for Crohn's disease, such as diet or microplastics exposure, change anti-microbial defenses in the gut and drive disease. In addition, we aim to define the protective immune defenses of the intestine to shape future therapeutic approaches to diahrreal 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.
Dr. Christine McDonald is an Associate Staff member in the Department of Inflammation & Immunity of the Lerner Research Institute and an Associate Professor of Molecular Medicine in the Cleveland Clinic Lerner College of Medicine. She also serves as Chair of the Institutional Biosafety Committee at both the Cleveland Clinic Main Campus and Cleveland Clinic Florida Research & Innovation Center.
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 in chronic disease. This research is supported by grants from the Department of Defense, the National Institutes of Health, and CURE4IBD.
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.
Postdoctoral Fellowship - University of Michigan Medical School
Department of Pathology
Laboratory of Gabriel Nunez, MD
Postdoctoral Fellowship - University of Michigan
Department of Biological Chemistry
Laboratory of Jack E. Dixon, PhD
Graduate Education - State University of New York at Stony Brook
PhD in Molecular & Cellular Immunology & Pathology
Laboratory of Nancy C. Reich-Marshall, PhD
Undergraduate Education - Macalester College
BA in Biology
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 diet and the global spread of eating a “Western diet” rich in fat, protein and processed foods parallels a recent, rapid, worldwide rise of CD development. Research in the McDonald lab is examining the effect of common dietary additives in a Western diet on the development of intestinal inflammation. Our data suggests that a widely used dietary additive changes both the composition and function of the normal intestinal microbiome and the antimicrobial defenses of the intestine. Similar to CD patients, these diet-induced changes don’t trigger disease by themselves, but when combined with other CD risk factors, results in intestinal inflammation. We are continuing this research using sophisticated molecular analyses in pre-clinical models that incorporate genetic risk factors, patient-derived cell systems, and in dietary studies with CD patients. As diet is a risk factor under our control, understanding how certain foods trigger disease could be a powerful and safe means to prevent its development in families with a history of CD or reduce disease flares in patients.
Another area of study is exploring the development of a new antimicrobial treatment for antibiotic-resistant bacteria wound 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 new antimicrobial enhances the innate immune response to bacteria mediated by the sensor protein, nucleotide-binding, oligomerization domain 2 (NOD2). Our studies show this antimicrobial agent increases the production and release of natural antibiotic factors from skin 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.
Peer Reviewed Publications:
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.
Zangara T., Bhesania N., Liu W., Cresci G.A.M., Kurowski J.A., & McDonald C. (2020) Impact of Diet on Inflammatory Bowel Disease Symptoms: An Adolescent Viewpoint, Crohn’s & Colitis 360, 2(4):otaa084. doi.org/10.1093/crocol/otaa084. PMCID: PMC6547010.
Jatana S.*, Homer C.R.*, Madajka M., Ponti A., Kabi A., Papay F., & McDonald C. (2018) Pyrimidine synthesis inhibition enhances cutaneous defenses against antibiotic resistant bacteria through activation of NOD2 signaling. Scientific Reports, 8(1): 8708. doi: 10.1038/s41598-018-27012-0. PCMID: PMC5992176. *co-first authors
McDonald C.*, Shen M.*, Johnson E.E., Kabi A., & Yao Q. (2018) Alterations in Nucleotide-Binding Oligomerization Domain 2 expression, pathway activation, and cytokine production in Yao Syndrome. Autoimmunity, 51(2):53-61. doi: 10.1080/08916934.2018.1442442. PMCID PMC6036904. *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. (2022) Inhibition of pyrimidine synthesis in murine skin wounds induces a pyoderma gangrenosum-like neutrophilic dermatosis accompanied by spontaneous gut inflammation. bioRxiv, 2022.12.20.521286. doi: https://doi.org/10.1101/2022.12.20.521286.
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.+ (2022) Abnormal thromobosis and neutrophil activation increases the risk of hospital-acquired sacral pressure injuries and morbidity in patients with COVID-19. medRxiv, 2022.07.07.22277374. doi:https://medrxiv.org/cgi/content/short/2022.07.07.22277374v1.
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.