UAB Synopsis, Vol. 24, No. 44, December 5, 2005
The career of William J. Koopman, MD, is a case study in creating bridges between medicine and research. Dr. Koopman retired on July 1, as chair of UAB's Department of Medicine, after leading the department for 11 years. The University of Alabama Board of Trustees named Dr. Koopman, who also earned the university's Distinguished Professor title, Chair Emeritus in September.
A talented physician and researcher, Dr. Koopman was an early pioneer in the field of targeted biologic therapy for autoimmune diseases. Since joining UAB in 1977, he has worked to uncover the best management for rheumatic diseases — from developing a mouse model of human rheumatoid arthritis (RA) to demonstrating the vital role of synovial tissue in the inflammation and joint destruction caused by RA. For this discovery, he is world renowned.
Specifically, his insights into the molecular biology of RA have inspired treatment possibilities. His research of immunoglobulin and its relationship to RA has led to development of such groundbreaking therapies as arthritis-fighting proteins, a monoclonal antibody, and a T-cell receptor peptide vaccine.
Dr. Koopman has led UAB rheumatology programs to national prominence as director of the Clinical Immunology and Rheumatology Division and founding director of UAB's Arthritis and Musculoskeletal Diseases Center, setting in motion innovative research, teaching, training, patient care, and community outreach that continue today.
The Sankyo Project
One initiative he established — a partnership with Sankyo Co., Ltd., of Japan to develop new rheumatoid arthritis therapies — has become the largest privately sponsored research program in UAB history. Since 1996, UAB has been working with Sankyo, Japan's second largest pharmaceutical company, on a variety of research topics. UAB was originally selected as the Tokyo-based firm's first research partner in the United States, and collaboration initially focused on rheumatic diseases. In 2002, the program expanded to include cancer research. Dr. Koopman has directed the program for the past 10 years.
Today, the UAB/Sankyo Program for Rheumatic Diseases and Cancer Research has produced the monoclonal antibody TRA-8, a breakthrough that was developed by UAB researchers. TRA-8 works by targeting specific sites on cell surfaces, called "death receptors," triggering apoptosis. The antibody has generated excitement among researchers because it kills active, proliferating cancer cells, while sparing surrounding healthy tissue. Tong Zhou, MD, associate professor of medicine, is leading this work. Investigators involved in the project include Donald Buchsbaum, PhD, Robert Kimberly, MD, Alexander Szalai, PhD, and Kurt Zinn, PhD.
"Drawing on our monoclonal antibody experience and strong research commitment with Sankyo, we hope to develop TRA-8 into the next promising cancer killer," Dr. Koopman says. "We look forward to working with Sankyo to offer this drug to as many patients as possible."
Examining University Research
"University research provides the vital link between the patient, the medical expert, and the development of new therapies," Dr. Koopman continues. "Physician scientists are nationally recognized experts and leaders in the field of translational clinical research and in strategic planning essential for development of new therapeutic agents."
Interaction with larger commercial companies, such as Sankyo, helps ensure success. UAB is in an enviable position, since drug companies now fund 70% of the clinical trials in the United States, and medical schools generally are receiving an ever-decreasing slice of this pie. UAB/Sankyo is also poised on the forefront of breakthroughs in gene therapy.
"Working on a molecular level, we're now rapidly moving toward delineating pathogenetic mechanisms and developing increasingly effective therapies, such as antitumor necrosis factor agents, for RA and other autoimmune disorders. Such advances, however, will pale in comparison to those we will see over the next several decades," Dr. Koopman says.
"Targeted RA therapy will increasingly be based on the patient's individual genotype," he explains. "If instituted promptly after diagnosis, I suspect that individualized therapy will ultimately induce clinical remission in a substantial fraction of patients at some point in the future."
Coming full circle, the chronic inflammatory response is also central to many other diseases under study at UAB, leading to a competitive extramural funding status. "Rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, inflammatory pulmonary and bowel disease, pulmonary fibrosis, chronic liver disease – all have recurring pathogenic themes suggesting overlapping pathogenetic mechanisms whereby scientists could intervene, identify patients at risk for severe disease, and offer more aggressive treatment.
"Physicians realize the great promise that drug innovations hold," Dr. Koopman concludes. "The key is to maintain a balance so that the business side of translational research never supersedes what is best for patients."