B.A. 1982 Boston University M.A., Ph.D. 1987 Boston University Jane Coffin Childs fellow, Roche Institute for Molecular Biology 1987-1989 Research Associate, Howard Hughes Institute, U.C.L.A. 1989-1990 Raymond & Beverly Sacker Scholar, Sloan-Kettering Institute 1990-1997
Biochemistry I & II, Advanced Topics in Biochemistry
Dr. Roepe’s graduate training was initially in the use of advanced physical techniques to study the properties of thin materials, and in the conductive properties of these materials. This developed into an interest in cell membranes, namely, biological examples of thin materials with ion specific conductivity. As a senior graduate student he began to appreciate the power of combining physical and molecular biological approaches for the study of biological membranes, thus, after receiving his Ph.D. he performed post-doctoral research at the Roche Institute of Molecular Biology, and then spent a year at the Molecular Biology Institute at the U.C.L.A. School of Medicine. These experiences led to an intense interest in the molecular basis of membrane – related drug resistance phenomena. In 1990 he accepted joint appointments in the Program in Molecular Pharmacology and Therapeutics at Memorial Sloan-Kettering Cancer Center and the Department of Pharmacology at Cornell University Medical College, where he studied pharmacology and worked on several problems related to tumor drug resistance and the transport of chemotherapeutic drugs across tumor cell membranes. In 1997 his laboratory moved to Georgetown University, where he is currently on the faculty of the Chemistry Dept., the Biochemistry and Molecular Biology Dept., and the Tumor Biology Program at the Lombardi Cancer Center. His training and independent research has been highly interdisciplinary but organized around the topics of membrane transport, drug resistance, and mechanisms of drug action.
More specifically, the Roepe laboratory hopes to elucidate mechanisms of resistance to cytotoxic drugs, so that better therapy can be developed, and to also design, synthesize and test new drugs based on that information. Defects in transmembraneous drug transport, ion transport, and cellular drug accumulation contribute to drug resistance, so one major focus of the laboratory is to understand this in molecular terms. Current projects include cloning and expression of antimalarial drug resistance proteins, development of biochemical and chemical biology approaches for studying their function, and design, synthesis and testing of novel antimalarial drugs based on that information. There are intriguing molecular similarities between drug resistance in tumors, certain bacteria and parasites, thus, this work may have broad implications. Our laboratory work remains highly interdisciplinary, and involves the use of recombinant DNA technology, cell biological and biochemical techniques, synthetic chemistry, and modern biophysical techniques such as single - cell photometry, laser confocal, and spinning disk confocal microscopy. Finally, the Roepe laboratory takes great pride in long term collaborative work. Key collaborations with laboratories at Georgetown, the NIH, Notre Dame, Case Western Reserve, Walter Reed Army Hospital, Johns Hopkins and Columbia have been very productive.
Grant Extends Professors' Malaria Research Georgetown University chemistry professors receive NIH-NIAID research grant for their interdisciplinary efforts in developing improved drugs to treat drug resistant malaria. April 7, 2005
Lekostaj, J., Natarajan, J.K., Paguio, M., Wolf, C. & Roepe, P.D. (2008) “Photolabelling of the Plasmodium falciparum Chloroquine Resistance Transporter (PfCRT) with a Novel per – Fluoroazido Chloroquine” Biochemistry 47(39):10394-406.
Cabrera, M., Natarajan, J.K., Paguio, M.F., Wolf, C., Urbach, J. S. & Roepe, P.D. (2009) “Chloroquine Transport in Plasmodium falciparum I: Influx and Efflux Kinetics for Live Trophozoite Parasites using a Novel Fluorescent Chloroquine Probe” Biochemistry 48: 9471-9481.
Paguio, M., Cabrera, M. & Roepe, P.D. (2009) “Chloroquine Transport in Plasmodium falciparum II: Analysis of PfCRT Mediated Drug Transport Using Proteoliposomes and a Fluorescent Chloroquine Probe” Biochemistry 48: 9482 – 9491.
Cabrera, M., Paguio, M. & Roepe, P.D. (2009) “Reduced Digestive Vacuolar Accumulation of Chloroquine is Not Linkecd to Resistance to Chloroquine Toxicity” Biochemistry 48:11152-11154.
Roepe, P.D. (2010) “PfCRT Function and Antimalarial Drug Resistance” Biochemistry (Current Topics Highlight Article) in press.