University of North Carolina at Chapel Hill
Area of Research:
Multidisciplinary research in microbiology, chemical biology, and epithelial cell biology
Primary Mentor:
Aadra Bhatt, PhD.
Assistant Professor of Medicine, Center for Gastrointestinal Biology and Disease Director, Mouse Phase 1 Unit, Lineberger Comprehensive Cancer Center. [email protected]
Mentor Team:
Hannah Atkins DVM, PhD, Dipl. ACVP
Assistant Professor
Department of Pathology and Laboratory Medicine
Division of Comparative Medicine
R. Balfour Sartor, MD
Midget Distinguished Professor of Medicine, Microbiology & Immunology,
Division of Gastroenterology and Hepatology
Co-Director, UNC Multidisciplinary IBD Center
Description of Potential Research Project(s):
Many medicines are used to manage Inflammatory Bowel Diseases (IBD) like Crohn’s or Ulcerative Colitis, but individual patient responses to them differ for reasons that are not well understood. For example, some patients enter remission with the recently approved Xeljanz, but many others do not. Moreover, Non-Steroidal Anti-inflammatory Drugs (NSAIDs) like Advil cause side effects or induce disease flares in some, but not all IBD patients. However, all IBD patients are advised to avoid NSAIDs, even though many would obtain relief from arthritis and other pain. Gut bacteria (microbiota) may contribute to the variable individual responses to IBD drugs. Accurately predicting detrimental or beneficial drug responses for individuals will guide precise, personalized strategies for optimal therapeutic approaches, thus improving quality of life for all IBD patients.
We study a bacterial enzyme called ß-glucuronidase (GUS) which converts NSAID metabolites into toxic forms that injure the intestinal epithelium and result in bloody diarrhea; blocking this conversion using investigational compounds protects the gut. We recently discovered that GUSs from IBD patient stools more robustly convert NSAID metabolites into toxic forms, compared to stools from healthy donors. NSAIDs could selectively flare disease in IBD patients whose intestines contain GUSs capable of converting NSAID metabolites into toxic forms. ß-glucuronidase presents a unique opportunity to mechanistically dissect drug-bug interactions in the gut, which we are doing using unique multidisciplinary approaches. UNC houses the National Gnotobiotic Rodent Resource Center, and is one of the leading GI research centers in the world. The Fellow can access a plethora of resources and a world-class vivarium, and will be mentored by internationally recognized translational and physician-scientists.
Additional Training Opportunities:
1. The Fellow will have multiple opportunities for presenting their work e.g,. at the Keystone meetings on the microbiome, the FASEB Scientific Research Conference on GI biology, and Digestive Diseases Week.
2. The Center for Gastrointestinal Biology and Disease (CGIBD) has a number of enrichment activities including a weekly seminar series, and a yearly “research day” consisting of poster presentations and networking opportunities with leading GI researchers. The CGIBD also has a Pilot grant program which provides funding for innovative research ideas. Several members of the CGIBD are DVMs with robust research programs at NC State University, with whom further collaborations may be developed.
3. The NC Translational and Clinical Sciences Institutute (NC TraCS) is funded by the National Center for Advancing Translational Sciences (NIH UL1TR002489), and provides workshops on Responsible Conduct of Research, Biostatistics, and grant writing for K- and R-level grants.
4. The UNC Office of Postdoctoral Affairs hosts a number of resources for the professional development of Fellows (e.g. preparing for job interviews, networking), a yearly Research Symposium consisting of a Keynote presentation by a Nobel Laureate. In addition, the OPA provides a vibrant social network for postdocs and their families.
5. The Office of Technology Commercialization which hosts monthly series in innovation, entrepreneurship, and commercializing research discoveries.
Contact Information for Interested Potential Trainees:
Aadra Bhatt, PhD.
Center for Gastrointestinal Biology and Disease, UNC Chapel Hill