DPLM Faculty Profiles — Dr. Jennette

Charles Jennette, MD

J. Charles Jennette, MD

Kenneth M. Brinkhous Distinguished Professor and Chair

Chief of Service of UNC Hospitals Clinical Laboratories

Office: 919-966-4676

E-mail: charles_jennette@med.unc.edu

Biographical Sketch

J. Charles Jennette, M.D. is Brinkhous Distinguished Professor and Chair of Pathology and Laboratory Medicine, Professor of Medicine, and Chief of Pathology and Laboratory Medicine Services at UNC Hospitals. He received his MD from UNC-CH in 1973. He completed anatomic and clinical pathology residency training at UNC, followed by a research fellowship in immunopathology at Scripps Clinic and Research Foundation in La Jolla, CA. Dr. Jennette joined the faculty of the School of Medicine at UNC in 1978 and has remained at UNC throughout his career. He is a diplomate of the American Board of Pathology in Anatomic and Clinical Pathology with Special Qualification in Immunopathology.

Dr. Jennette's service, teaching and research activities focus on kidney disease. He is Executive Director of the UNC Nephropatholgy Laboratory, which evaluates approximately 2,000 renal biopsy specimens per year, is Co-Director (with Dr. Ronald J. Falk) of the Glomerular Disease Collaborative Network, which coordinates kidney disease research by approximately 300 nephrologists throughout the Southeastern United States, and is Associate Director of the UNC Kidney Center, which is an interdisciplinary consortium with the mission of improving all aspects of kidney disease prevention and treatment. Dr. Jennette’s research is directed at understanding the causes, and improving the diagnosis and treatment of kidney diseases, especially those caused by inflammatory and immunologic mechanisms. Dr. Jennette has published over 250 journal articles, 150 book chapters, and 17 books. He is editor of Heptinstall’s Pathology of the Kidney and serves on the editorial boards of professional journals dealing with pathology or kidney diseases.

Research Interests

Dr. Jennette’s current research focuses on inflammatory vascular disease (vasculitis and glomerulonephritis) caused by anti-neutrophils cytoplasmic autoantibodies (ANCA), which are a major cause for the most common form of aggressive glomerulonephritis and systemic small vessel vasculitis in adults. In collaboration with Dr. Hong Xiao and Dr. Peiqi Hu, he utilizes animal models of ANCA disease discovered in their laboratory that is induced by mouse anti-myeloperoxidase (anti-MPO) antibodies and is mediated primarily by activation of neutrophils. Activation of the alternative complement pathway is critically involved in the pathogenesis of disease in this model. ANCA-activated neutrophils release factors that activate complement, which in turn primes neutrophils for further activation by ANCA. These effects and other ANCA-mediated pathogenic events depend on generation of C5a by alternative pathway activation and on engagement of C5a receptors on neutrophils. Blockade of this critical pathogenic step abrogates disease induction, which suggests a possible novel therapeutic strategy in humans. Recent ongoing studies using this mouse model as well as patient samples indicate that Fc gamma receptors are involved in pathogenesis. Genetic variations among mouse strains have a dramatic influence on disease severity. Genomic studies are underway to identify the genes responsible for these differences in disease severity. Candidate genes or genetic polymorphisms will be studied in parallel in patients with ANCA disease.

Experiments also are underway to assess the induction of disease by antibodies against specific MPO sense and anti-sense peptides. Pathogenic epitopes are being mapped using human-mouse chimeric molecules. The hypothesis is that one or more, but not all of these chimeric molecules will induce antibodies that cause disease, thus identifying the portion of the MPO molecule that is the target of pathogenic antibodies.

Publications

View list of publications from PubMed