While today's pharmaceuticals are directed toward fewer than 2 percent of the proteins encoded by the human genome, thousands of genes have been implicated in the broad spectrum of rare diseases that affect humanity. Facilitating the discovery and development of drugs for treating rare and underserved diseases is an important area of focus for the National Institutes of Health (NIH).
In collaboration with investigators and foundations, Dr. Inglese's laboratory explores novel strategies to identify chemical modulators targeting the molecular underpinnings of disease pathophysiology. Dr. Inglese develops and validates biochemical and cell-based phenotypic assays for use in the screening of chemical libraries. He also uses gene silencing technologies and chemogenomic libraries to reveal secondary targets mediating the function of primary genetic abnormalities. Assay designs encompass the measurement of gene expression, epigenetic and post-translational regulation, cell-surface and nuclear receptor binding, signal transduction, and metabolic enzymes, as well as the biological activity of entire pathways and the functional variation resulting from the genomic diversity of pathogenic organisms.
In order to support the development of a more efficient drug discovery paradigm, Dr. Inglese's laboratory engages in the evaluation, development, and refinement of high throughput techniques and novel assay technologies for small molecule discovery. For example, he and his colleagues developed an improved process for testing large chemical libraries by integrating the resolving power of the pharmacologic dose-response relationship with the speed and accuracy of automated HTS. The resulting technology has become a fundamental asset at the National Center for Advancing Translational Sciences (NCATS), and Dr. Inglese's group is now enhancing this methodology to unlock the immense biological potential of natural product extracts.
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Last Updated: February 27, 2012