Dr. Ian S. Zagon
Distinguished Professor, Distinguished Educator, and Director of the Program on Education in Human Structure
Hershey Medical Center, Penn State University
Ian S. Zagon, Ph.D., is Professor of Neuroscience and Anatomy at The Pennsylvania State University, College of Medicine, Hershey, Pennsylvania. Dr Zagon holds membership in the Specialized Cancer Research Center, Intercollege Graduate Program in Genetics, Cell and Molecular Biology Graduate Program Neuroscience Graduate Program, M.D./Ph.D. Program, and the Integrative Biosciences Graduate Program-Molecular Medicine, Neuroscience, and Cell and Developmental Biology.
Dr Zagon was born in New York City. In 1972, Dr Zagon accepted a position as Assistant Professor in the Department of Anatomy, University of Miami Medical School.
Dr Zagon relocated to the Department of Anatomy (now the Department of Neuroscience and Anatomy) at The Pennsylvania State University College of Medicine, in Hershey in 1974. His early interests focused on the etiology and pathogenesis of brain tumors. However, another research project that served as the root of investigations for over a quarter of a century was initiated at this time: opioid peptides, opioid receptors, and growth, and a team effort with Dr Patricia J. McLaughlin, Associate Professor of Neuroscience and Anatomy, was formed. These early studies examined the repercussions of maternal opioid abuse (methadone, morphine, and heroin) on the outcome of offspring, particularly those concerned with the nervous system. These researchers learned that such drugs of abuse have a marked negative impact on brain development, and that these alterations influence the infant, adolescent, and adult anatomy of the nervous system as well as cognition and behavior. Based on observations in the late 1970s about exogenous opioids, as well as experiments with opioid antagonists in developing animals and in cancers, the research turned toward whether the endogenous opioids - first discovered in 1975 - acted as growth factors. In a series of papers in the 1980s, he provided evidence supporting this hypothesis. A key observation was that continuous exposure to potent opioid antagonists such as naltrexone accelerated growth of normal and neoplastic cells in tissue culture and in vivo, but shorter exposure times inhibited growth. The explanation for this retardation in growth was related to the upregulation of opioids and receptors by naltrexone treatment, and the interaction of these opioids and receptors after naltrexone was no longer present - hence, causing a supersensitivity.
In subsequent studies, the native pentapeptide, methionine enkephalin, was found to be the most potent endogenous opioid influencing growth; this peptide was termed Opioid Growth Factor (OGF) to signify its role as a growth factor and to distinguish it from its neuromodulatory function. Subsequent work with receptor binding analysis revealed a nuclear-associated receptor for OGF, OGFr, originally termed the zeta opioid receptor but renamed after the molecular structure was identified. Biochemical, cellular, and molecular work on the receptor resulted in the cloning and sequencing of the cDNA for OGFr in rat, mouse, and human, along with the chromosomal identity on human chromosome 20q13.3. The OGF-OGFr axis has been studied in vivo and in vitro, and the interaction of OGF-OGFr defined in development, homeostatic renewal, neoplasia, and injury. OGF serves as a tonically active, constitutively expressed, inhibitory growth factor, and displacement of OGF-OGFr interfacing using opioid antagonists, antibodies to OGF, and antisense technology with OGFr, showed an acceleration in growth. Recent studies have reported that cancer cells may have a dysfunction of OGF and/or OGFr, providing an advantage for growth.
In other scientific collaborations, Dr Zagon joined with Dr Steven Goodman of the Department of Physiology at Penn State in the discovery of non-erythroid spectrin in the 1980s, and defined this system in the developing and adult nervous system. In the 1990s and continuing to the present, Dr Zagon collaborated with Dr Jill P. Smith, a Professor in the Division of Gastroenterology in the Department of Medicine at Penn State, and this research team reported the original observation of a new receptor - the CCK-C receptor - which functions in the growth of neoplasia. Currently, Phase I and Phase II trials are testing OGF as a therapeutic modality in pancreatic cancer patients. Additional collaborations at Penn State have examined the acceleration of corneal epithelial wound healing in normal and diabetic conditions by naltrexone with Dr Joseph W. Sassani, Department of Ophthalmology, the establishment of the OGF-OGFr axis in angiogenesis with Dr John Blebea, Division of Vascular Surgery in the Department of Surgery, the use of OGF in treatment of squamous cell carcinomas of the head and neck, and the molecular nature of OGFr with Dr Michael Verderame, Department of Medicine.
Dr Zagon has been a co-organizer of national and international meetings on developmental biology and cancer, and he serves - and has served - on the editorial board of five journals. Dr Zagon has authored more than 240 publications, as well as 200 presentations and invited talks, and has published three books. He has received numerous grants from a variety of agencies, including the National Institutes of Health, the American Cancer Society, and the American Heart Association, and has been awarded six patents. For the past 19 years, Dr Zagon has received a Distinguished Teaching Award by the medical students.
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Dr. Zagon and His Research Team