The Pediatric Surgery Research Laboratory is headed by two Principal Investigators, Gail Besner, MD and David Brigstock, PhD. Basic research is broadly focused on mechanisms of cell growth regulation, with special emphasis on the role of polypeptide growth factors. Laboratory personnel include surgical residents, post-doctoral residents, research associates, and graduate students. In addition, undergraduate and medical students are given the opportunity to work on projects during the summer months. The research laboratories are located in The Research Institute at Nationwide Children's Hospital, a multi-disciplinary research facility that is attached to Children's Hospital. All of the laboratories in The Research Institute are occupied by research groups that are headed by full-time geographic faculty members of the Ohio State University's Department of Pediatrics and Department of Surgery. The Pediatric Surgery Laboratories occupy approximately 2000 sq. ft. and expertise spans the broad areas of cell biology, biochemistry and molecular biology.
The Besner research group is interested in a growth factor known as heparin-binding EGF-like growth factor (HB-EGF), which Dr. Besner initially identified in 1990. The focus of Dr. Besner's research is on the effect of HB-EGF in the intestine, as a cytoprotective factor against intestinal injury. The translational component of Dr. Besner's research involves a disease process known as neonatal necrotizing enterocolitis (NEC), which results in intestinal necrosis in newborn babies, especially those born prematurely. The long-range goal of Dr. Besner's work is the prophylactic and therapeutic treatment of high-risk neonates with HB-EGF, in order to prevent and treat this often devastating disease. Clinical trials of HB-EGF therapy for the prevention of NEC are scheduled to begin in 2008.
Dr. Brigstock's group is investigating the biology of connective tissue growth factor (CTGF). CTGF acts to promote fibroblast proliferation, migration, adhesion, and extracellular matrix formation, and its over-production is proposed to play a major role in pathways that lead to fibrosis, especially those that are TGF-beta-dependent. This includes fibrosis of major organs, fibro-proliferative diseases, and scarring. CTGF also appears to play a role in extracellular matrix remodeling that occurs in normal physiological processes such as embryogenesis, implantation, and wound healing. CTGF has been implicated in a diverse variety of processes that include neovascularization, transdifferentiation, neuronal scarring, atherosclerosis, cartilage differentiation, and endochondral ossification. Broad areas of focus in Dr. Brigstock's lab include structure-function analysis of the CTGF protein, CTGF transcriptional regulation, CTGF signaling pathways, and the role of CTGF in driving fibrosis in the liver and pancreas. Molecular, cellular and biochemical approaches are used to study CTGF actions in cell culture systems as well as for investigating the role of CTGF in vivo in rodent fibrosis models, including CTGF transgenic mice. Novel anti-fibrotic therapies that target CTGF biosynthetic or signaling pathways are currently under development.