The Pediatric Surgery Basic Science Research Laboratories focuses on three major areas of study. Dr. Gail Besner’s laboratory studies heparin-binding EGF-like growth factor (HB-EGF) and its ability to protect the intestines from various forms of injury. These research projects continue to be funded by the National Institutes of Health and include:
Studies of the effects of HB-EGF on stem cells
Stem cell transplantation in protection of the intestines from injury
Production of tissue engineered intestine
Determination of the mechanisms and signaling pathways used by HB-EGF in intestinal cytoprotection
Studies of the effects of HB-EGF in several established animal models of intestinal injury
The second area of investigation focuses on the production of tissue engineered vascular grafts. Dr. Christopher Breuer’s laboratory includes:
Investigating the cellular mechanisms underlying vascular neotissue formation
Exploring the biomechanical principles controlling vascular tissue formation
Rational design of strategies to inhibit the development of tissue engineered vascular graft stenosis
Development of tissue engineered heart valves
The third area of interest is the role played by Connective Tissue Growth Factor (CTGF) in scarring and fibrosis. These studies are led by Dr. David Brigstock and focus on the understanding fibrogenic pathways in the liver after injury. This NIH-funded work includes the following projects:
Role of CTGF in stimulating collagen production in hepatic stellate cells
Evaluation of CTGF as a marker of chronic liver disease
Regulation of CTGF expression in hepatic stellate cells by microRNAs (miRs)
Intercellular transfer of CTGF mRNA or regulatory miRs by nanosized exosomes
Characterization of the miR payload in circulating exosomes to establish a molecular signature to allow non-invasive evaluation of the severity of liver fibrosis
Targeting of fibrogenic pathways using therapeutic exosomal strategies
The Pediatric Surgery Clinical Research Program focuses on outcomes and clinical translational research. The Deans-Minneci laboratory has developed a comprehensive surgical outcomes research program which employs a wide range of methodologies in order to determine optimal interventions for the management of surgical diseases and the minimization of post-operative complications. Initial areas of focus include:
Non-operative management of appendicitis
Patient activation and shared decision-making in surgery
Comparative effectiveness studies of surgical interventions for congenital anomalies
Management and interventions for non-accidental trauma
Gail E. Besner, M.D.
Significant accomplishments have occurred in the Besner laboratory this year. Dr. Besner’s lab is currently in its 21st year of continuous funding from the NIH to support her basic science research on heparin-binding EGF-like growth factor (HB-EGF). In addition, she recently received a Technology Development Fund Grant and an Ohio Third Frontier Grant for her innovative work on the production of tissue engineered intestine. She was recently appointed to a four-year term as a member of the National Advisory Council of the National Institute of General Medical Sciences at the National Institutes of Health. Dr. Besner’s research was presented at multiple international and national meetings this year. She presented her research as an invited guest speaker at the International Symposium of Pediatric Hepatobiliary Disease, Tongji Hospital, Wuhan, China, and was the Jay and Margie Grosfeld Lecturer in Pediatric Surgery at the American Pediatric Surgical Association annual meeting. In addition, she was a Visiting Professor at the Department of Pediatric Surgery, Sichuan Provincial People’s Hospital, Chengdu, China, and at Rush University, Chicago, IL. Trainees from Dr. Besner’s laboratory presented their research at the annual meetings of the American Pediatric Surgical Association, the Surgical Section of the American Academy of Pediatrics, and the Academic Surgical Congress. Many publications have resulted from this year's work. In addition, trainees from Dr. Besner’s laboratory received several awards under her mentorship. Dr. Jia Wei won the Research Award at The Research Institute at Nationwide Children’s Hospital Research Day, Dr. Terry Rager won the James King Research Award and the First Place Best Poster Award in The Ohio State University Department of Surgery, and Dr. Laura Boomer won the Rosencrantz Resident Best Clinical Research Award of the American Academy of Pediatrics Section on Surgery. Also, work from Dr. Besner’s laboratory conducted by Dr. Yu Zhou received the BioMed Central Translational Research Award for their manuscript entitled “Enteric nervous system abnormalities are present in human necrotizing enterocolitis: potential neurotransplantation therapy.” Dr. Besner currently serves as Chair of the American College of Surgeons Surgical Research Committee.
Christopher K. Breuer, M.D.
My most significant achievements in research this year have revolved around establishing a translational research laboratory at Nationwide Children's Hospital and The Ohio State University. The Breuer laboratory is in the midst of the first FDA-approved clinical trial evaluating the use of tissue engineered vascular grafts in congenital heart surgery. They enrolled two patients into the trial and performed the first implantation of a tissue engineered vascular graft at Nationwide Children’s Hospital in March 2014. Other significant achievements include the opening the large animal surgery suite in the research institute, where studies of the safety and efficacy of the use of tissue engineered tracheas using an ovine model are being conducted. Finally, the Breuer laboratory continues to expand the capabilities of their world-class microsurgery core including development of the first murine heart valve replacement model. They now have a fully operational facility for performing bench to the bedside translational research in the field of tissue engineering at Ohio state University.
David R Brigstock, Ph.D.
Dr. Brigstock continues his studies on mechanisms of fibrosis in the liver and is developing innovative methods by which it can be assessed and treated. He is currently investigating novel regulation of hepatic stellate cells (HSC; a usually quiescent cell type that becomes activated during liver injury and drives the fibrotic response) by nanovesicles, or “exosomes”, that are secreted by the cells and shuttle complex molecular information between them. He has shown that exosomes trasnsfer critical molecular signals between neighboring HSC, including connective tissue growth factor (CTGF) which drives fibrogenic pathways in HSC and microRNA-214 (miR-214) which dampens CTGF production. Current work suggests that the balance between pro- and anti-fibrotic molecules in the exosome payload determines the extent of the fibrotic response during injury. He has also shown that the exosomal molecular payload (including CTGF and miR-214) in circulating exosomes reflects dynamic changes in their production in fibrotic livers, showing that the exosomal concentration of these and other constituents (protein, mRNA, miRs) may offer improved diagnostic options for non-invasive assessment of fibrosing liver disease.
Katherine J. Deans, M.D. & Peter C. Minneci, M.D.
Drs. Deans and Minneci continue to develop the Center for Surgical Outcomes Research at Nationwide Children’s Hospital. Ongoing areas of investigation in their laboratory include non-operative management of appendicitis, patient activation and shared decision-making in surgery, management of trauma with a focus on non-accidental trauma, quality improvement projects for pediatric surgical procedures, and comparative effectiveness studies of surgical interventions for congenital anomalies and acquired pediatric surgical diseases. They have obtained grant funding to support their work from several national agencies including the Patient Centered Outcomes Research Institute (PCORI) and the Agency for Healthcare Research and Quality. In addition, their research fellow, Dr. Jason Sulkowski, successfully completed an NIH T32 Training Grant award under their mentorship. Over the past year, the Deans/Minneci laboratory has presented their research at the annual meetings of the American Pediatric Surgical Association, the Surgical Section of the American Academy of Pediatrics, the Academic Surgical Congress, the American College of Surgeons Clinical Congress, Pediatric Academic Societies, the Pediatric Trauma Society, and the Annual Symposium for ECMO and the Advanced Therapies for Respiratory Failure.