Medicinal Chemistry, Drug Discovery, Preclinical candidate Development, Therapeutic candidates for Alzheimer’s disease (AD) and CNS disorders.
Dr. John is an accomplished medicinal chemist and leads the Drug Discovery Laboratory in the Department of Neurology at UCLA. Dr. John is a member of the Alzheimer’s Disease Program in the Mary S. Easton Center for Alzheimer’s Disease. Previously Dr. John was with Athena Neurosciences and Elan Pharmaceuticals for ~18 years where he was part of project teams developing drug candidates for CNS disorders. These efforts led to clinical candidates for AD and an approved product for multiple sclerosis. His work at Elan included development of potent inhibitors for BACE and γ-secretase, key enzymes in formation Aβ and amyloid plaques. After his industry tenure, he joined the Buck Institute where he led the Alzheimer’s Drug Discovery Network with Dr. Dale Bredesen, the Founding CEO of the Institute. Dr. John is an inventor on over 100 pending or issued patents on compounds for CNS related targets.
The focus of the AD research in the lab include programs to discover molecules targeting varied mechanisms implicated in the disease that affect both phosphorylation and release of tau (p-tau) along with those that modulate postsynaptic uptake of p-tau that could suppress the spread and progression of the disease. These programs are supported by corporate partners and NIH. They include: (1) discovery of molecules that increase the sAPPα, a preclinical candidate from this class DDL-110, has advanced into clinical development for AD by a corporate partner; (2) discovery of molecules that target and reverse the ApoE4-mediated risk factor in AD; (3) discovery of molecules that target secreted clusterin (sCLU) in AD; (4) discovery of corticotrophin factor (CRF) receptor modulators that reduce p-tau and reverse memory deficits; (5) discovery of molecules that target sorting protein-related receptor with A-type repeats (SORLA); and (6) discovery of mimetics of Humanin (HN) as potential therapeutics for AD. The lab is also developing its microfluidic based synthetic exosome (SE) for delivery of protein, antibody and nucleotide based therapeutics for AD and other CNS disorders including SE-ASM for Niemann Pick disease as part of a corporate collaboration.