Christine McDonald Laboratory

Research

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.

Selected Publications

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

Preprints:

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.