Target Validation, Lead Discovery, and Lead Optimization for Neglected Diseases

My group focuses on the discovery and preclinical development of new therapeutic leads for neglected diseases. We place a major focus on discovering new therapeutic chemotypes, determining their mechanism of action, and conducting proof-of-concept studies in pharmacokinetic/pharmacodynamic (PK/PD) models of disease. All of the projects are intended to deliver well-validated compounds that have suitable pharmacokinetic and toxicology profiles for detailed in vivo studies.  During my independent career, both historically and currently, the projects in my laboratory have been split roughly equally between oncology and protozoal diseases.

Our work spans the entire process from initial identification of new chemical hits through optimization of late leads in animal models and finally to the design and execution of human clinical trials. To date, our work has identified dozens of potential new leads for these diseases with novel mechanisms of action or novel applications.  We have contributed to repurposing drugs for clinical trials for ependymoma, infantile ALL, and medulloblastoma; contributed a repurposed clinical candidate for retinoblastoma; and produced a novel clinical candidate, (+)-SJ733, for the treatment of malaria that is currently entering Phase 2 trials (https://clinicaltrials.gov/ct2/show/NCT02867059).