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James Inglese, Ph.D. Deputy Director NIH Chemical Genomics Center Director Biomolecular Screening and Profiling Division NIH Chemical Genomics Center B.A. Rensselaer Polytechnic Institute, 1984 Ph.D. Pennsylvania State University, 1989 (301) 217-5723 (301) 217-5736 jinglese@mail.nih.gov Building 9800, Room 3005 9800 Medical Center Dr Rockville, MD 20892 Selected Publications Recruitment for Automation Engineers James Inglese: Uniting Biology and Chemistry in High Throughput

Dr. Inglese investigates the interactions of small molecules with biological targets. His expertise is in developing, optimizing, and miniaturizing biochemical and cell-based assays for studying cell-surface and nuclear receptors, signal transduction and metabolic enzymes, and targeted pathways and genomes. Currently, he is developing the infrastructure of the NIH Chemical Genomics Center (NCGC), the first component of a nationwide network of screening centers that will produce innovative chemical probes for use in biological research and drug discovery.

Today’s pharmaceuticals are directed toward fewer than 2% of the proteins encoded by the human genome, leaving ample opportunity for the discovery of myriad novel disease-intervention options. Of the approximately 25,000 human genes unearthed by genomic sequencing, those capable of modulating human disease remain relatively unknown. Identifying proteins involved in disease without the insights gained from years of intensive biomedical research is a daunting task. In an attempt to overcome such obstacles, Dr. Inglese applies state-of-the-art, high-throughput (HT) screening and assay technologies to the search for novel chemical probes that can regulate protein-protein interactions and gene expression.

A veteran of the pharmaceutical and biotechnology industry, Dr. Inglese has developed many biological assay methods, including one of the first high-sensitivity fluorescence G protein-coupled receptor assays. He pioneered the use of laser-scanning imaging, a technology that enables the use of cellular and particle-based assays in whole cell ligand-binding studies. He also developed chemical methodologies to incorporate cAMP-dependent protein kinase (PKA) sites into proteins, peptides, and small molecules permitting straightforward PKA-dependent labeling of ligands for use in radiometric assays. Most recently, he explored the use of naturally occurring protein domains, in combination with protein evolution techniques, to create antibody surrogates for the detection of post-translationally modified peptides and proteins. Such engineered domains have been used successfully in the development of protease and phosphatase assays for HT screening.

For NCGC, Dr. Inglese is developing and refining HT techniques for novel assay technologies and small molecule discovery processes. These assays may include bioactivity confirmation assays, potency determinations, and phenotypic cell-based assays focused on small molecule modulators of protein-protein interactions. To aid in the identification of chemical ligands for proteins of unknown function, he will lead a major effort to amass and analyze a diverse spectrum of interesting compounds that may not have been tested in the past because they were not considered to have drug-like potential. This collection will include many of the natural products classified as cellular metabolites and biosynthetic intermediates.

HT technologies, which allow for simultaneous collection of data from thousands of individual assays, often involve a fusion of biology, automation, and complex data analysis. Thus, their success is contingent on assembling a multidisciplinary team of scientists, engineers and bioinformatics experts. That is why, when fully developed, NCGC will have a large, technically diverse staff with expertise in several areas, including biomolecular screening and profiling, chemistry and informatics.

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Last Updated: August 1, 2008