Hon Wai Koon, PhDAssistant Professor, Division of Digestive Diseases, David Geffen School of Medicine at UCLA
Dr. Koon’s research is focused on the synthetic mechanism and roles of the antimicrobial peptide Cathelicidin in inflammatory bowel disease, intestinal infections, colorectal cancer, obesity, and diabetes. Cathelicidin is a natural endogenous anti-microbial peptide that is protective to its host as a part of innate immune system. Our laboratory was the first to show that endogenous cathelicidin ameliorates dextran sulfate (DSS) colitis via bone marrow-derived immune cells. We also found increased expression of cathelicidin in monocytes/macrophages in the colonic mucosa of ulcerative colitis patients. Cathelicidin-deficient mice develop more severe bacterial penetration into intestinal mucosa and associated intestinal inflammation than wild-type mice. Therefore, we understand that endogenous cathelicidin may be a protective response to intestinal infection and inflammation. Moreover, intracolonic administration of the cathelicidin peptide ameliorates C. difficile-mediated colitis in mice. We are now studying the role of cathelicidin in the change of intestinal microflora in the development of obesity and diabetes. Dr. Koon is now investigating the role of a non-peptide cathelicidin-mimic, Ceragenin CSA13, in the protection against intestinal inflammation, C. difficile infection, obesity, and diabetes. This protection may be related to change of intestinal microflora. CSA13 is more chemically stable than natural cathelicidin and may be suitable for clinical use. Our research establishes a new direction of research in digestive diseases using microflora study, clinically relevant human primary cells, fresh intestinal biopsies, biologically induced colitis animal models, and system biology approaches.
Recent Relevant Publications
- Koon HW, Shih DQ, Chen J, Bakirtzi K, Hing TC, Law I, Ho S, Ichikawa R, Zhao D, Xu H, Gallo R, Dempsey P, Cheng G, Targan SR, Pothoulakis C. Cathelicidin signaling via the Toll-like receptor protects against colitis in mice. Gastroenterology. 2011 Nov;141(5):1852-63.e1-3. PubMed PMID: 21762664; PubMed Central PMCID: PMC3199285.
- Hing TC, Ho S, Shih DQ, Ichikawa R, Cheng M, Chen J, Chen X, Law I, Najarian R, Kelly CP, Gallo RL, Targan SR, Pothoulakis C, Koon HW. The antimicrobial peptide cathelicidin modulates Clostridium difficile-associated colitis and toxin A-mediated enteritis in mice. Gut. 2013 Sep;62(9):1295-305. PubMed PMID: 22760006; PubMed Central PMCID: PMC3737259.
Active Funding in Microbiome-Related Research
|Funding Agency/Grant Number:||NIH 1R03DK103964-01A1|
|Title:||“Role of cathelicidin in obesity and diabetes”|