Stuart Lipton, MD/PhD
About
Titles
Biography
Neurologist/neuroscientist Stuart Lipton, MD, PhD is a renowned expert in dementia. He was trained at Cornell University, the University of Pennsylvania, and Harvard University. In addition to running a basic-science laboratory, he has an active clinical neurology practice focusing on dementia and general neurology. Lipton completed his PhD thesis research with John Dowling at Harvard, followed by clinical residency and a postdoctoral fellowship at Harvard with Torsten Wiesel during the time that Wiesel won the Nobel prize. He was then on the Harvard faculty for over 20 years before moving to La Jolla as founding director of a new neuroscience center in 2000. He is best known for first describing the mechanism of action and contributing to the clinical development of the FDA-approved Alzheimer’s drug, memantine (Namenda®), and for discovering the posttranslational redox modification, protein S-nitrosylation.
Recently, Lipton 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 and improving neurobehavioral deficits. Lipton’s group also characterized HIV-related pathways to neuronal damage, discovered the NR3 (now known at GluN3) family of modulatory NMDA receptor subunits, characterized the molecular pathways for protecting neurons with Erythropoietin, and discovered the transcription factor MEF2C. His group showed that MEF2C activity is regulated by S-nitrosylation and 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. Lipton was awarded the Ernst Jung Prize in Medicine and is an elected fellow of the AAAS. He recently received an Alzheimer’s Disease Association Award, a Michael J. Fox Foundation Grant, and an NIH Director’s Grant Award.
Appointments
Education & Training
- Research Fellow
- Harvard Medical School, Dept. of Neurobiology (1983)
- Board Certification
- American Board of Psychiatry & Neurology, Neurology (1982)
- Resident and Chief Resident in Neurology
- Brigham & Women's Hospital, Beth Israel Deaconess Medical Center, Boston Children's Hospital (1981)
- Intern in Medicine
- Beth Israel Deaconess Medical Center, Harvard Medical School (1978)
- MD/PhD
- University of Pennsylvania, Biochemistry & Biophysics (1977)
- BA
- Cornell University, Neurobiology and Immunology (1971)
Research
Publications
2024
Single‐Cell Patch‐Clamp/Proteomics of Human Alzheimer's Disease iPSC‐Derived Excitatory Neurons Versus Isogenic Wild‐Type Controls Suggests Novel Causation and Therapeutic Targets
Ghatak S, Diedrich J, Talantova M, Bhadra N, Scott H, Sharma M, Albertolle M, Schork N, Yates J, Lipton S. Single‐Cell Patch‐Clamp/Proteomics of Human Alzheimer's Disease iPSC‐Derived Excitatory Neurons Versus Isogenic Wild‐Type Controls Suggests Novel Causation and Therapeutic Targets. Advanced Science 2024, e2400545. PMID: 38773714, DOI: 10.1002/advs.202400545.Peer-Reviewed Original ResearchAbundance of individual proteinsIsogenic wild-type controlsSingle-cell (scHuman AD brainsWild-type controlsSingle-cellAlzheimer's diseaseMulticellular organismsSingle-cell physiologyAD brainTherapeutic targetIndividual proteinsProteomic informationGenetic mutationsProteinProteomicsProtein expressionHiPSC-neuronsExcitatory neuronsElectrophysiological statusDisease statesPhysiologyElectrophysiological dataNeuronsNeuronal levelMetabolic Bypass Rescues Aberrant S‐nitrosylation‐Induced TCA Cycle Inhibition and Synapse Loss in Alzheimer's Disease Human Neurons
Andreyev A, Yang H, Doulias P, Dolatabadi N, Zhang X, Luevanos M, Blanco M, Baal C, Putra I, Nakamura T, Ischiropoulos H, Tannenbaum S, Lipton S. Metabolic Bypass Rescues Aberrant S‐nitrosylation‐Induced TCA Cycle Inhibition and Synapse Loss in Alzheimer's Disease Human Neurons. Advanced Science 2024, 11: 2306469. PMID: 38235614, PMCID: PMC10966553, DOI: 10.1002/advs.202306469.Peer-Reviewed Original ResearchTricarboxylic acidOxidative phosphorylationAlzheimer's diseaseSynapse lossSynaptic lossPathological correlate of cognitive declineHuman AD brainsTCA cycle inhibitionMetabolic flux experimentsAberrant S-nitrosylationPostmortem human AD brainIsogenic wild-typeAssociated with synaptic lossDysfunctional mitochondrial metabolismMitochondrial bioenergetic functionProtein S-nitrosylationModel of ADMitochondrial energy metabolismCell-permeable derivativeCorrelate of cognitive declineAD brainMitochondrial metabolismEnzyme functionHiPSC-based modelsBioenergetic functionEnzymatic and non-enzymatic transnitrosylation: “SCAN”ning the SNO-proteome
Nakamura T, Lipton S. Enzymatic and non-enzymatic transnitrosylation: “SCAN”ning the SNO-proteome. Molecular Cell 2024, 84: 191-193. PMID: 38242098, DOI: 10.1016/j.molcel.2023.12.018.Peer-Reviewed Original Research
2023
“Dark Matter” Pathways of Protein Transnitrosylation Injure Synapses in Alzheimer’s Disease
Lipton S. “Dark Matter” Pathways of Protein Transnitrosylation Injure Synapses in Alzheimer’s Disease. Free Radical Biology And Medicine 2023, 208: s7. DOI: 10.1016/j.freeradbiomed.2023.10.390.Peer-Reviewed Original Research
2005
Response to Comment on "S-Nitrosylation of Parkin Regulates Ubiquitination and Compromises Parkin's Protective Function"
Lipton S, Nakamura T, Yao D, Shi Z, Uehara T, Gu Z. Response to Comment on "S-Nitrosylation of Parkin Regulates Ubiquitination and Compromises Parkin's Protective Function". Science 2005, 308: 1870c-1870c. PMID: 15976289, DOI: 10.1126/science.1110353.Peer-Reviewed Original ResearchProtection against HIV-1 gp120 and HIV-1 Tat neurotoxicity
Kandanearatchi A, Nath A, Lipton S, Masliah, E, Everall I. Protection against HIV-1 gp120 and HIV-1 Tat neurotoxicity. 2005, 201-210. DOI: 10.1093/oso/9780198526100.003.0019.Peer-Reviewed Original ResearchHIV-1 Tat neurotoxicityViral protein gp120HIV-1 gp120HIV infectionInflammatory changesNeuronal damageTat neurotoxicityPoor prognosisProfound dementiaPathogenetic mechanismsNeurocognitive disordersProtein gp120Cognitive impairmentGp120Mechanisms of toxicityCellular damageNeurotoxicityTranscription (STAT) proteinsHIVPrognosisPathogenesisDementiaInfectionImpairmentBrain
1993
hMEF2C Gene Encodes Skeletal Muscle- and Brain-Specific Transcription Factors
McDermott J, Cardoso M, Yu Y, Andres V, Leifer D, Krainc D, Lipton S, Nadal-Ginard B. hMEF2C Gene Encodes Skeletal Muscle- and Brain-Specific Transcription Factors. Molecular And Cellular Biology 1993, 13: 2564-2577. DOI: 10.1128/mcb.13.4.2564-2577.1993.Peer-Reviewed Original ResearchMyocyte enhancer-binding factor 2Transcription factorsCharacterization of cDNA clonesBind nuclear proteinsTissue-specific patternsTissue-specific isoformsTrans-activation activityBrain-specific transcription factorMode of regulationMEF2 transcription factorsMuscle-specific enhancerCDNA clonesAlternative exonsNuclear proteinsDNA bindingPosttranscriptional processesFunctional characterizationBrain transcriptsGenesSkeletal muscle-TranscriptionMyogenic differentiationCortical neuronsPotential targetMRNA levels
1978
Cessation of smoking followed by Prinzmetal's variant angina and diffuse esophageal spasm.
Lipton S, Markis J, Pine M, Paulin S, Lindsay H. Cessation of smoking followed by Prinzmetal's variant angina and diffuse esophageal spasm. New England Journal Of Medicine 1978, 299: 775-6. PMID: 692554.Peer-Reviewed Original Research