Stuart Lipton, MD, PhD

Biography

Stuart Lipton is best known for first describing the mechanism of action and contributing to the clinical development of the FDA-approved Alzheimer’s drug, memantine & for discovering the posttranslational redox modification known as protein S-nitrosylation. Recently, Lipton and colleagues combined memantine with S-nitrosylation chemistry to produce a new drug called NitroSynapsin, which displays disease-modifying activity in animal models of Alzheimer’s disease, both protecting synapses & improving neurobehavioral deficits.

Lipton’s group also characterized HIV-related pathways to neuronal damage, discovered the NR3 family of modulatory NMDA-type glutamate receptor subunits in the brain, characterized the molecular pathways for protecting neurons with Erythropoietin, & discovered the transcription factor MEF2C. His group showed that MEF2C activity is regulated by S-nitrosylation & serves as a master switch for neurogenesis from human neural stem cells. Dysregulated MEF2C is involved in the pathogenesis of Parkinson’s disease, Alzheimer’s disease, Autism-Spectrum Disorder, and Vascular dementia.

Ongoing research in the lab is focused on 2D human induced pluripotent stem cell (hiPSC)-derived cultures and 3D cerebral organoid models of neurodegenerative and neurodevelopmental disease and aberrant redox/S-nitrosylation pathways leading to synaptic damage.

Using these approaches, the Lipton group is developing novel drugs to combat Alzheimer’s disease, Parkinson’s disease, Vascular dementia (VaD), and other neurodegenerative disorders, as well as Autism-Spectrum Disorder and Intellectual and Developmental Disabilities. Tissue culture models complement whole-animal approaches. A plethora of techniques is employed, including chemical biology, molecular biology, patch-clamp electrophysiology, calcium imaging, and neurobehavioral paradigms.

BRAIN Funded Projects

MEF2C Haploinsufficiency Drug Discovery – Potential to Improve ASD Phenotypes

Optimize lead compounds discovered by Lipton’s lab in order to develop drug candidates to treat a specific type of autism.

Recent & Selected Publications

Trudler D, Ghatak S, Lipton SA. Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases. Int J Mol Sci. 2021;22(15):8196. Published 2021 Jul 30. doi:10.3390/ijms22158196

Lipton SA, Li H, Zaremba JD, et al. Autistic phenotype from MEF2C knockout cells. Science. 2009;323(5911):208. doi:10.1126/science.323.5911.208b

BRAIN Synchrony Symposia presentations