Since joining the faculty, Dr. Orringer's research activities have focused upon the membrane transport properties of the normal human erythrocyte and on its disordered physiology in a variety of pathological states, especially the sickle hemoglobinopathies.  Dr. Orringer received a Research Career Development Award from the NHLBI in 1982, and he has held consistent peer-reviewed grant support for well over 15 years.  Upon assuming the Directorship of the GCRC, Dr. Orringer began to focus more and more of his efforts on clinical and translational research.  He has been a national leader in the ongoing, NIH-funded clinical trials which demonstrated that hydroxyurea reduces the frequency of the painful vaso-occlusive events experienced by adults with sickle cell anemia.  In an attempt to improve upon the beneficial effects of hydroxyurea and to lower the amount of this potentially toxic agent to which sickle cell patients are being exposed, Dr. Orringer developed an individual IND in which he proposed to combine hydroxyurea with clotrimazole, an imidazole antifungal agent that has been shown to inhibit potassium efflux from the sickle erythrocyte through a calcium-activated K channel (i.e., the Gardos pathway).  Dr. Orringer is presently testing his hypothesis with support from an FDA orphan drug grant.   Finally, in addition to studies designed to prevent crises, Dr. Orringer is also involved in studies using hemoglobin-based blood substitutes, rheologically-active compounds, and nitric oxide, all of which are being given to sickle cell patients in an effort to terminate or at least shorten acute painful crises.

In addition to his own research activities, Dr. Orringer has been consistently involved in the training of young scientists.  He is participant in numerous NIH-funded post-doctoral training programs. He has been actively involved in the development of new training opportunities and the establishment of career paths for postdoctoral fellows and junior faculty members, particularly those seeking to become clinical investigators.  For example, in 1989, soon after assuming the Directorship of the GCRC, he established the UNC GCRC Fellowship Program.  These awards were made annually to senior-level fellows from the School of Medicine.   In addition to these institutional GCRC Fellowships, Dr. Orringer assisted a total of 11 junior faculty members obtain NIH translational research grants referred to as Clinical Associate Physician (or CAP) awards, six of which are currently ongoing. By contrast, only one CAP grant had been awarded to a UNC physician during the 15 year period before Dr. Orringer became the Program Director of the UNC GCRC.  In 1993, Dr. Orringer and the UNC GCRC competed successfully for a "Task Award" contract from the National Institute for Environmental Health Sciences (NIEHS).  An important component of this award was a training program with slots for both physicians and nurses who had an interest in and commitment to environmental health and medicine.  Between 1994 and 1999, UNC was able to identify and recruit six excellent physicians and two nurses into this unique training program.  Finally, in mid-1995, Dr. Orringer assumed the Directorship of the UNC MD-PhD Program, which at that time was quite modest, with a total enrollment of only 12 students.  Dr. Orringer agreed to do everything possible to build the UNC MD-PhD Program into a nationally-recognized entity, one capable of competing for a Medical Scientist Training Program (MSTP) grant from the NIH.  During the first three years under his leadership, the UNC MD-PhD Program grew from 12 to 30 students.  In January, 1998, Dr. Orringer and his team submitted to the NIH a proposal for an MSTP grant.  With the recent funding of this award, the UNC MD-PhD Program is now receiving the national recognition necessary to compete for the best possible students.  Additionally, the funds received from the MSTP award over the next five years will enable enrollment in the Program to reach 60 students by 2003.