Executive Director, Neuro-Oncology and Brain Cancer Center, Cleveland Clinic,
Case Western Reserve University Medical Center
Professor of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University
MD, Northwestern University
PhD in Biophysics, University of Chicago
Dr. Rosenfeld started his career at the University of Alabama, Birmingham Medical School. He dedicated his medical career to brain cancer after his mother passed away from the disease in 1978. In 1995, he became director of the school’s Brain Tumor Program in 1995. Under his leadership, the program underwent a marked expansion in both clinical and translational research. This culminated in Dr. Rosenfeld’s being awarded a Brain Cancer Specialized Center of Research Excellence (SPORE) grant by the National Cancer Institute in 2002–one of only two nation-wide. Dr. Rosenfeld’s research, which has been funded by the National Cancer Institute and the National Institute of Neurological Diseases and Stroke, focuses on novel ways of pharmacologically-blocking brain tumor growth and invasiveness by targeting the molecular motors that drive mitosis and cell motility. He is a Fellow of the American Neurological Association, has served as a member of the Editorial Board of the Journal of Biological Chemistry, is a peer reviewer for over 15 scientific journals, and is a member of the Developmental Therapeutics study section. He has also served as the Educational Program Director for the Society for Neuro-Oncology (1999) and as a member of the NCI/NINDS Progress Review Group in Neuro-Oncology.
My laboratory is interested in understanding at a molecular level how the physiologic requirements placed on an enzyme shape its function. We are addressing this concern by focusing on a group of enzymes called “molecular motors”. These enzymes drive a wide variety of physiologic processes, from whole cell motility to vesicle transport to separation of the chromosomes during mitosis. As such, they represent potential targets for the development of new therapies for diseases characterized by abnormal cell motility and cell growth, such as cancer. We utilize a variety of spectroscopic methodologies, including fluorescence resonance energy transfer, fluorescence anisotropy decay, and resonance Raman spectroscopy to examine how functionally important domains within motors contribute to generating force and movement. We also combine these structurally-sensitive probes with transient state kinetics to determine the timing and sequence of conformational changes in each motor’s mechanochemical cycle.
I have largely focused my research on two classes of molecular motors–the myosins and kinesins. Current research in my laboratory on myosin is examining the sequence of structural changes that occur in transport myosins, such as myosins V and VI, that explain how these motors are capable of moving long distances on actin filaments without dissociating–a feature called “processivity”. My work on the kinesin family of motors has largely focused on the mechanisms of processivity of kinesin I. However, I have more recently been interested in studying those kinesins that drive formation of the mitotic spindle, referred to as “mitotic” kinesins.
Finally, I am applying the spectroscopic assays of motor function developed in my laboratory to a microtiter well platform, in collaboration with investigators at the University of Pittsburgh, to screen for small molecule inhibitors of mitotic kinesins, which may ultimately be applicable clinically as inhibitors of mitosis.
Dr. Rosenfeld quoted in New York Times article on Ted Kennedy Diagnosis