The Lindsley research group at Vanderbilt University is a unique environment for graduate and postgraduate training. The primary focus of research in our group is drug discovery, medicinal chemistry and synthetic chemistry (total synthesis). The Lab features state-of-the-art technology, typically found only in major pharmaceutical companies, and a diverse group of scientists: staff synthetic and medicinal chemists, experienced Ph.D. Medicinal Chemists from Big Pharma, staff chromatography specialists and a diverse pool of graduate students pursuing Ph.D.s in Chemistry, Pharmacology and Chemical & Physical Biology.
Members of our lab will collaborate with other members of the Pharmacology, Drug Metabolism and Clinical Pharmacology departments to pursue small molecule hits from high throughput screens, perform lead optimization studies to develop structure-activity-relationships (SAR) and ultimately deliver small molecules with acceptable properties to validate novel targets/mechanisms in in vivo animal models of target diseases. The molecular targets of interest are kinases, GPCRs, ion channels, nuclear hormone receptors and protein-protein interactions, with an emphasis on allosteric modulation as opposed to classical agonism/antagonism. Therapeutic areas of interest span cancer, neuroscience (schizophrenia, anxiety, pain, sleep, Parkinson’s disease) and endocrinology (diabetes, obesity). Students will be exposed to every phase of classical drug discovery. As Director of Medicinal Chemistry in the Vanderbilt Program in Drug Discovery, and Director of the Vanderbilt Specialized Chemistry Center (MLPCN), training in my laboratory will be broad and involve organic synthesis, medicinal chemistry, pharmacology and drug metabolism. For many programs in the neuroscience area, students will have the opportunity to also develop radioligands for binding assay development and PET tracers for imaging studies.
Another focus in the Lindsley group is parallel synthesis and the development of new technologies for library synthesis. The lab has state-of-the-art microwave synthesis technology, a mass-directed HPLC purification platform, automated normal and reverse phase chromatography, analytical and preparative chiral HPLC, and a large collection of monomers and polymer-supported reagents. There are a number of projects directed at synthesizing libraries of small molecule protein-protein inhibitors, target family-directed libraries and other drug-like small molecule libraries for use in high throughput screening efforts.
The third area of interest in our group is synthetic organic chemistry. Students will have the opportunity to work on synthetic methodology projects as well as partial and total synthesis projects. Since October 2006, three total syntheses (carpanone, dispyrin, ciliatimides A-C) have been completed with many more nearing completion.