Bios for CDD Town Hall: Therapeutically Relevant Bioassays
Dr. Nathan P. Coussens is a Senior Research Scientist in the Division of Pre-Clinical Innovation at the National Center for Advancing Translational Sciences (NCATS). He received his Ph.D. in biochemistry from the University of Iowa, where he applied structural and biophysical approaches to the study of host-pathogen interactions. As a postdoctoral fellow of the Interdisciplinary Immunology Program at the University of Iowa, he utilized X-ray crystallography and thermodynamic binding studies to inform the development of small molecules that target a host evasion mechanism exploited by families of pathogenic bacteria.
Prior to joining NCATS in 2013, Dr. Coussens was a postdoctoral fellow at the National Cancer Institute where he combined biophysical studies, cell biology, and high-resolution imaging to interrogate molecular signaling events initiated by the T cell antigen receptor. At NCATS, Dr. Coussens applies his diverse scientific background to establish and optimize novel biochemical and cell-based methodologies for high-throughput screening. He works with a highly collaborative and multidisciplinary team to develop small molecule probes relevant to a variety of human diseases.
In 2014, Dr. Coussens was appointed Associate Scientific Editor of the Assay Guidance Manual, a growing online guide dedicated to best practices in drug discovery and development that has become the go-to resource for scientists in industry and academia.
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.
In studying these phenomena we use a battery of interdisciplinary techniques, including recombinant DNA methods, yeast genetics, cell culture, and general wet biochemistry. In addition, we have pioneered the se of novel single-cell fluorescence imaging techniques to analyze membrane transport phenomena for individual living cells under constant perfusion. For example, in one particularly exciting recent advance we have analyzed the pH of the digestive vacuolar compartment of living malarial parasites growing within human red blood cells. In collaboration with the Tom Wellems laboratory at NIH, we are now uing this technique to investigate the role of specific genetic mutations associated with the emergence of chloroquine resistance.
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