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BESNER LABORATORY
Dr. Besner's research centers around a growth factor known as heparin-binding EGF-like growth factor (HB-EGF), first identified by Besner et al. in 1990. The central theme of Dr. Besner's research involves the effect of HB-EGF as an intestinal cytoprotective agent. Multiple lines of evidence, both in vitro and in vivo, have been obtained in Dr. Besner's laboratory to support the ability of HB-EGF to protect the intestines from injury. HB-EGF plays a vital role in postischemic regeneration due to its mitogenic, chemoattractant, antiapoptotic and anti-inflammatory effects. In vitro, HB-EGF is a potent mitogen and chemoattractant agent for intestinal epithelial cell lines. In addition, it protects intestinal epithelial cells from necrosis and apoptosis, in part by decreasing reactive oxygen and nitrogen radical formation. In vivo, we have used several rodent models of intestinal injury to demonstrate the intestinal cytoptotective effects of HB-EGF. We have shown that HB-EGF protects the intestine in the face of intestinal ischemia/reperfusion injury, hemorrhagic shock and resuscitation and experimental necrotizing enterocolitits. 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. In addition to funding of Dr. Besner's work from the National Institutes of Health, Dr. Besner is working with industry to bring HB-EGF to the bedside in human clinical trials, expected to begin in 2009.
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| Education |
| 1991 |
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Residency |
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Pediatric Surgery |
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Buffalo Children's Hospital, Buffalo, NY |
| 1989 |
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Fellowship |
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Surgical Research |
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Boston Children's Hospital Harvard Medical School, Boston, MA |
| 1987 |
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Residency |
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General Surgery |
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Brigham & Women’s Hospital, Boston, MA |
| 1982 |
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M.D. |
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Medicine |
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University of Cincinnati, Cincinnati, Ohio |
| Professional Experience |
| 2005- PRES |
Associate Program Director, Residency in Pediatric Surgery, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, Ohio |
| 2003- PRES |
Professor of Surgery and Pediatrics, The Ohio State University, Division of Pediatric Surgery at Nationwide Children's Hospital, Columbus, OH |
| 2001- PRES |
Member, Integrated Biomedical Sciences Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio |
| 1994- Pres |
Member, Comprehensive Cancer Center, The Arthur James Cancer Hospital and Research Institute, Ohio State University, Columbus, OH |
| 1992- Pres |
Member, Molecular and Cellular Developmental Biology Program, Ohio State University, Columbus, OH |
| 2004- 2008 |
Full-time Member, Surgery, Anesthesia and Trauma Study Section, National Institutes of Health |
| 1997- 2003 |
Associate Professor of Surgery and Pediatrics, The Ohio State University, Division of Pediatric Surgery at Nationwide Children's Hospital, Columbus, OH |
| 1999- 2001 |
Co-Director, Medical Scientist Training Program, Ohio State University, Columbus, OH |
| 1991- 1997 |
Assistant Professor of Surgery and Pediatrics, Ohio State University, Division of Pediatric Surgery at Columbus Children's Hospital, Columbus, OH |
| 1991- 1991 |
Pediatric Surgeon, Children's Hospital, Buffalo, NY |
| 1989- 1989 |
Surgical Research, Children's Hospital, Boston, MA |
| 1987- 1989 |
Research Fellow, Department of Surgery, Children's Hospital and Harvard Medical School, Boston, MA
Mentors: Dr. M. Judah Folkman and Dr. Michael Klagsbrun
Project: Identification of a novel growth factor (heparin-binding EGF-like growth factor (HB-EGF)) from cultured human macrophages. |
| 1987- 1987 |
Surgeon, Brigham & Women's Hospital, Boston, MA |
| 1977- 1978 |
Undergraduate Research Fellowship, Cornell University, Division of Nutritional Sciences, Ithaca, NY
Mentor: Dr. V. Utermohlen
Project: The effect of exogenously added fatty acids on cell mediated immunity. |
BESNER LABORATORY STAFF
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Principal Investigator:
Gail E. Besner, M.D.
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| Selected Publications |
| El-Assal O, Paddock H, Marquez A, Besner G: HB-EGF Gene Disruption is Associated with Impaired Angiogenesis, Delayed Intestinal Restitution, and Poor Survival after Intestinal Ischemia in Mice. J Pediatr Surg 43:1182-1190, 2008. |
| Mehta V, Zhou Y, Radulescu A, Besner G: HB-EGF Stimulates eNOS Expression and Promotes eNOS Dependent Angiogenesis. Growth Factors (in press). |
| Feng J and Besner G: HB-EGF Promotes Enterocyte Proliferation and Migration in Neonatal Rats with NEC. J Pediatr Surg 42:214-220, 2007. |
| Rocourt D, Mehta V, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) Decreases Pro-Inflammatory Cytokine Expression after Intestinal Ischemia/Reperfusion Injury. J Surg Res 139:269-273, 2007. |
| Rocourt D, Mehta V, Besner G: Heparin-Bidning EGF0Like Growth Factor (HB-EGF) Decreases Neutrophil-Endothelial Cell Interactions. J Surg Res 141:262-266, 2007 |
| El-Assal O, Radulescu A, Besner G: HB-EGF Preserves Mesenteric Microcirculatory Blood Flow and Protects against Intestinal Injury in Rats Subjected to Hemorrhagic Shock and Resuscitation. Surgery 142:234-242, 2007. |
| Mehta V, Besner G: HB-EGF Promotes Angiogenesis in Endothelial Cells via P13-kinase and MAPK Signaling Pathways. Growth Factors 25:253-263, 2007. |
| Feng J, Mehta V, El-Assal O, Wu D, Besner G: Tissue Distribution and Plasma Clearance of Heparin-Binding EGF-Like Growth FActor (HB-EGF) In Adult and Newborn Rats. Peptides 27:1589-1596, 2006 |
| Feng J, El-Assal O, Besner G: Heparin-Binding EGF-Like Growth Factor Decreases the Incidence of Necrotizing Enterocolitis in Neonatal Rats. J Pediatr Surg 41:144-149, 2006. |
| Feng J, El-Assal O, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) Reduces Intestinal Apoptosis in Neonatal Rats with NEcrotizing Enterocolitis. J Pediatr Surg 41:742-747, 2006. |
| Feng J, El-Assal O, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) and Necrotizing Enterocolitis. Seminars in Pediatric Surgery 14:167-174, 2005. |
| Martin A and Besner G: Timing, Route and Dose of Administration of Heparin-Binding EGF-Like Growth Factor (HB-EGF) in Protection against Intestinal Ischemia-Reperfusion Injury. J Pediatr Surg 40:1741-7, 2005. |
| Mehta V and Besner G: HB-EGF Inhibits Cytokine-Induced NF-κB Activiation and Nitric Oxide Production via Activation of the P13-Kinase Pathway. J Immunol 175:1911-1918, 2005. |
| El-Assal O and Besner G: HB-EGF Enhances Restitution After Intestinal Ischemia/Reperfusion via P13-k/Akt and MEK/ERK1/2 Activation. Gastroenterology 129:609-625, 2005. |
| El-Assal O and Besner G: Heparin-binding EGF-Like Growth Factor (HB-EGF) and Intestinal Ischemia-Reperfusion Injury. Seminars in Pediatric Surgery 13:2-10, 2004 |
| Xia G, Rachfal A, Martin A, Besner G:
Upregulation of Endogenous Heparin-Binding EGF-Like Growth Factor
(HG-EGF) Expression after Intestinal Ischemia/Reperfusion Injury. J Investig Surgery 16:1-7, 2003.
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| Xia G, Martin A, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) Downregulates Expression of Adhesion Molecules and Infiltration of Inflammatory Cells After Intestinal Ischemia/Reperfusion Injury. J Pediatr Surg. 38:434-439, 2003. |
| Mehta V and Besner G: Inhibition of Nuclear Factor Kappa-β (NF-kβ) Activation and its Target Genes by Heparin-Binding EGF-Like Growth Factor (HB-EGF). J Immunol 171:6014-6022, 2003 |
| Pillai S, Turman M, Besner G: Heparin-binding EGF-like growth factor (HB-EGF) is a cytoprotective growth factor for intestinal epithelial cells. J Pediatr Surg 33:973-979, 1998.
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| Pillai S, Hinman C, Luquette M, Nowicki P, Besner G: Heparin-binding EGF-like growth factor (HB- EGF) protects rat intestine from ischemia/reperfusion injury. J Surg Research 87, 225-231, 1999.
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| Michalsky MP, Kuhn A, Mehta V, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) Decreases Apoptosis in Intestinal Epithelial Cells in Vitro. J Pediatr Surg, 36, 1130-1135, 2001. |
| Xia G, Lara-Marquez, M, Luquette M, Haque A, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) Decreases Inducible Nitric Oxide Synthase and Nitric Oxide Production after Intestinal Ischemia/Reperfusion Injury. Antioxidants and REDOX Signaling 5, 919-930, 2001 . |
| Michalsky M, Lara-Marquez M, Chun L, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) is Present in Human Amniotic Fluid and Breast Milk. J Pediatr. Surg. 37, 1-6, 2002. |
| Lara-Marquez M, Mehta V, Michalsky M, Fleming J, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) Down regulates Pro-Inflammatory Cytokine-Induced Nitric Oxide and inducible Nitric Oxide Synthase Production in Intestinal Epithelial Cells. Nitric Oxide: Biology and Chemistry 6, 142-152, 2002. |
| Xia G, Martin A, Michalsky M, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) Preserves Crypt Cell Proliferation and Decreases Bacterial Translocation After Intestinal Ischemia/Reperfusion Injury. J Pediatr. Surg. (in press). |
| Kuhn A, Xia G, Martin A, Michalsky M, Besner G: Heparin-Binding EGF-Like Growth Factor (HB-EGF) Decreases Oxygen Free Radical Production In Vitro and In Vivo. Antioxidants and REDOX Signaling (in press). |
| Kuhn A, Xia G, Mehta V, Glenn S, Michalsky M, Besner G: Heparin-binding EGF-Like Growth Factor (HB-EGF) Decreases Oxygen Free Radical Production In Vitro and In Vivo. Antioxiants and REDOX Signaling 4:639-646, 2002. |
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