University or Institution

North Carolina State University

Area of Research:

The Intestinal Regenerative Medicine Laboratory focuses on clinical and basic science research that aims to identify improved means to determine tissue viability as well as to develop technology and therapeutics that enhance intestinal epithelial regenerative potential. The lab specifically studies the role of intestinal stem cells in modulating mucosal barrier repair following severe ischemic injury.

Primary Mentor:

Liara M. Gonzalez, DVM, PhD, DACVS

Associate Professor of Gastroenterology and Equine Surgery. Co-Director, Center for Gastrointestinal Biology and Disease, North Carolina State University

Email: [email protected]

 

MENTOR TEAM:

Anthony Blikslager, DVM, PhD, DACVS, Dept. of Clinical Sciences, North Carolina State University

Jody Gookin, DVM, PhD, DACVIM, Dept. of Clinical Sciences, North Carolina State University

Christopher Dekaney, PhD, Dept. of Molecular Biological Sciences, North Carolina State University

Andrew Barbas, MD, Dept. of Surgery, Duke University

Description of Potential Research Projects:

Over the last decade, limited progress has been made in patient survival following intestinal transplantation (IT). As IT is a vital treatment option for intestinal failure, a need exists to understand the pathophysiology of graft failure. Ischemia-reperfusion (IR) is a key contributor to allograft failure in clinical cases causing epithelial loss that damages the crypt where intestinal stem cells (ISC) reside. Currently, intestinal cold storage (CS) is used prior to IT and has been associated with IR injury. In a currently funded project (DOD PR181265), a novel storage method of normothermic machine perfusion (NMP) will be utilized to improve viability of intestinal grafts. Our preliminary data suggest that NMP improves graft viability and we have assembled a multidisciplinary team to use preclinical models to rigorously compare the effects of NMP vs CS on immune activation, gut microbiota, stem cells and graft viability.

We hypothesize that NMP reduces allograft injury that results from IR by two modes of action: 1) minimizing immune activation that primes the graft for rejection, and 2) improving the viability and function of the immune cells that promote intestinal integrity and regeneration. This hypothesis will be tested using two preclinical models: 1) Ex vivo simulation of pre-transplant storage conditions (CS vs NMP) of human intestinal grafts, 2) In vivo evaluation of storage method (CS vs NMP) in the porcine IT model. This project represents the lab’s long-standing commitment to advance the development and utilization of the pig as a more translational model of human/veterinary clinically relevant disease.

Additional Training Opportunities:

Trainees at NC State benefit from strong collaborative relationships between the CVM, University of North Carolina (UNC-CH), and Duke University medical schools. There are extensive opportunities to attend seminars and conferences related to gastroenterology, translational research, and professional development. Exposure to human gastrointestinal health issues include weekly Center for Gastrointestinal Biology and Research (CGIBD) Seminar Series, the annual CGIBD Research Forum, as well as teaching, leadership, mentorship and research seminars offered by NCTraCS (UNC-CH); and weekly transplant group research updates (Duke). Comparative and basic science training include weekly GI Journal Club (NC State), the annual CVM Research Forum, and technical training within the Gonzalez and Barbas Laboratories. Available professional development at NC State includes Comparative Medicine and Translational Research Training Program (T32) seminars, the Preparing Future Leaders program, and the College’s Office of Research led K Grant Writing Group (monthly workshops that guide trainees in submitting NIH career development awards). The Fellow will hone their mentorship skills working directly with undergraduate and veterinary students in the CMI Summer Interdisciplinary Research Initiative and the NIH T35 or Boehringer-Ingelheim Veterinary Scholars programs. Further opportunities to teach and develop mentoring skills include participation in selectives, case-based problem-solving sessions, and wet labs for veterinary students. The Comparative Biomedical Sciences Teaching Certificate program and the Academy of Educators (AoE) offer formal training in teaching. AoE members gain exposure and training in best practices in education, opportunities to network with internal and external university

Contact Information for Interested Potential Trainees:

 

Liara M. Gonzalez, DVM, PhD, DACVS

Phone: (919) 513-6919

Email: [email protected]

Website: http://go.ncsu.edu/GonzalezLab