Bios: 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 in the Department of Physics at Boston University was initially in the use of advanced physical techniques to study the properties of cell membranes. Through collaborative work with molecular biologists in the Gobind Khorana laboratory, he began to appreciate the power of combining physical and molecular biological approaches for the study of biological membranes. After receiving his Ph.D. he pursued post-doctoral research on membrane transporters 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 fostered an interest in the molecular basis of membrane – related drug resistance phenomena. In 1990 he accepted joint appointments in Molecular Pharmacology and Therapeutics at Memorial Sloan-Kettering Cancer Center and in Pharmacology at Cornell University Medical College, where he began work on drug resistance and transmembrane drug transport. When the work branched out to include studies of drug resistant malaria, his laboratory moved to Washington DC, where he is currently on the faculty of the Chemistry Dept., the Biochemistry and Cellular and Molecular Biology Dept., and the Tumor Biology Program at Georgetown University. His training and independent research has been interdisciplinary but organized around the topics of membrane transport, drug resistance, and mechanisms of drug action. His advocacy work for the US government and a variety of NGOs centers on topics related to neglected infectious diseases, drug resistance and drug development, and better health care delivery.
The Roepe laboratory works to elucidate mechanisms of drug resistance and to translate this knowledge towards development of better therapy. Defects in trans-membraneous drug transport, ion transport, and cellular drug accumulation contribute to most examples of cellular drug resistance, so a major focus of the laboratory is to understand these phenomena in molecular terms. Current projects include cloning and expression of antimalarial drug resistance proteins, development of biochemical, immunological and chemical biology approaches for studying their function, and design, synthesis and testing of novel antimalarial drugs and drug combinations 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. The Roepe laboratory’s work remains highly interdisciplinary, and involves the use of recombinant DNA technology, cell biological, immunological and biochemical techniques, synthetic chemistry, and modern biophysical techniques such as single – cell photometry, laser confocal, and spinning disk confocal microscopy. The Roepe laboratory takes great pride in long term collaborative work. Key collaborations with laboratories at the NIH (NCATS and NIAID), the Johns Hopkins University, U.C. San Diego, Columbia Univ., Notre Dame, Case Western Reserve, Walter Reed Army Institute of Research, and at Georgetown have been particularly productive.
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