Meet the Team
The DDL team consists of accomplished scientists and skilled technicians from multiple scientific disciplines who have joined the lab to find effective, safe therapeutics for the treatment of neurodegenerative disease, with a focus on Alzheimer's disease. Led by Varghese John, Ph.D, the team works together to conduct most aspects of preclinical drug discovery, from development of phenotypic screens and target validation, to medicinal chemistry for hit-to-lead optimization, in vitro ADME-T studies for lead advancement, in vivo pharmacokinetic and pharmacodynamic testing for target engagement, and lead confirmation.
Idealogy & Vision
The goal of our research is to discover why the aging brain is at risk for Alzheimer's disease (AD) and based on this knowledge, develop strategies to prevent, delay, and cure AD. To achieve these goals we rely on unique approaches to understanding the mechanisms underlying AD, to therapeutic discovery, and to design of clinical trials. We use a "Pharma" model in an academic setting wherein we design primary (including high-throughput screening, HTS), secondary and tertiary in vitro assays and a variety of in vivo studies appropriate for each compound series and target, to identify new therapeutics than can advance to clinical testing in AD (or other neurodegenerative disease) patients.
The DDL approach is based on the hypothesis that AD results from an imbalance in an extensive array of networks. Current monotherapeutic approaches may address a single network dysfunction, but this has not lead to an efficacious new AD therapy in more than 10 years. Rather than focusing on a single target, we are developing a more comprehensive Systems Therapeutic Approach that includes both pharmacological and nonpharmacological components to correct the various known network imbalances in AD.
The DDL embraces all stages of early drug discovery: target validation, development of phenotypic screens, medicinal chemistry for hit-to-lead optimization, in vitro ADME/T, in vivo pharmacokinetic (PK)/pharmacodynamic (PD) testing for target engagement studies for lead advancement, and lead confirmation. Members of the DDL each have a specialty and focus, and their efforts are coordinated to advance drug development.