Associate Professor, Thoracic and Head & Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center
Featured Speaker: Jonathan M. Kurie, M.D.
Associate Professor, Thoracic and Head & Neck Medical Oncology, The University
of Texas M.D. Anderson Cancer Center
Jonathan Kurie, M.D., graduated from the Lawrenceville School, the University of North Carolina (B.A.), and East Carolina University (M.D.). He completed postdoctoral training in internal medicine at the Medical College of Georgia, in biotechnology at the National Cancer Institute (NCI), and in medical oncology at Memorial Sloan-Kettering Cancer Center. Board certified in internal medicine and medical oncology, he received outstanding training in basic molecular oncology research with Dr. Michael Potter at the NCI and with Dr. Ethan Dmitrovsky at the Sloan-Kettering Institute, where Dr. Kurie produced highly original work. Based on his recognized accomplishments, he was recruited to The University of Texas M.D. Anderson Cancer Center as Assistant Professor in the Department of Thoracic and Head & Neck Medical Oncology; subsequently, he rose through the academic ranks to become a tenured Associate Professor at the center.
Dr. Kurie is nationally recognized for his studies in retinoid signaling in the aerodigestive tract. His research focuses on mechanisms by which retinoids inhibit the proliferation of human bronchial epithelial cells. He discovered that retinoids inhibit MAP kinase signaling pathways by activating the expression of MAP kinase phosphatases, suppressing the mitogenicity of peptide growth factors in the bronchial epithelium. These retinoid effects are blocked by MAP kinase kinase-4 (MKK4), which directly phosphorylates retinoid X receptor (RXR) and inhibits the transactivation of RXR heterodimeric complexes. These findings were published in Molecular and Cellular Biology, The Journal of Clinical Investigation, and The Journal of Biological Chemistry.
In the clinical lung cancer prevention field, Dr. Kurie advanced our understanding of 9-cis retinoic acid. This was accomplished through a phase I trial (published in Clinical Cancer Research) and an ongoing phase III trial examining 9-cis retinoic acid's efficacy in the reversal of biomarkers of bronchial premalignancy in former smokers. He completed a landmark study of 4-hydroxyphenylretinamide, a retinoid with potent apoptotic effects, in the reversal of biomarkers of bronchial premalignancy in active smokers (reported in Clinical Cancer Research). He also played a leading role in implementing a novel laser autofluorescence bronchoscopic technique that is potentially more sensitive than white light bronchoscopy in the detection of bronchial premalignancy (reported in Journal of the National Cancer Institute).
Dr. Kurie is the recipient of a Sidney Kimmel Foundation Award and an American Cancer Society Career Development Award. He was recognized by The University of Texas M. D. Anderson Cancer Center for research excellence as the center's nominee for the Burroughs Wellcome Fund Award, and he received a University Cancer Foundation Award and the Physicians Referral Service Award. He is a peer-reviewer for the National Institutes of Health (NIH) study sections, and he captured impressive peer-reviewed funding from competitive sources, including NIH R01 and R29 grants and a Research Project Grant from the American Cancer Society. He is Project Leader of an NIH Lung Cancer SPORE and an NIH U01 grant (Animal Models of Human Cancer Consortium). In 2001, Dr. Kurie was elected to The American Society for Clinical Investigation.
Dr. Kurie made major contributions to the basic scientific and clinical retinoid chemoprevention fields. His demonstration that MKK4 phosphorylates RXR changed the belief that MKKs are dedicated to the phosphorylation of MAP kinases, adding a level of complexity to MAP kinase signaling not previously appreciated. This finding likely has diverse biologic consequences, because RXR is the heterodimeric partner of a variety of steroid and orphan nuclear receptors. His discovery that retinoid and MAP kinase signaling pathways act in a mutually antagonistic manner uncovers an important mechanism by which lung cancers develop de novo resistance to retinoids. This is an important clinical problem that has limited the chemopreventive benefit of retinoid therapy. Some lung cancers harbor constitutively active Ki-ras and over-express specific peptide growth factor receptors that are potent activators of the MAP kinase pathway. Based on Dr. Kurie's findings, strategies to inhibit MKK4 activation would enhance retinoid actions in lung cancer chemoprevention. Ongoing basic scientific and clinical studies should validate this hypothesis.
Learning Objectives:
Early Diagnosis and Chemoprevention of Lung Cancer: New Molecular Approaches—Jonathan M. Kurie, M.D.