Adjunct faculty typically have an academic or research appointment at another institution and contribute or collaborate with one or more School of Medicine faculty members or programs.
Adjunct rank detailsStuart Lipton, MD, PhD
Adjunct Professor of NeurologyAbout
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Titles
Adjunct Professor of Neurology
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)
- 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)
- PhD
- University of Pennsylvania, Biochemistry & Biophysics (1977)
- MD
- University of Pennsylvania, Biochemistry & Biophysics (1977)
- BA
- Cornell University, Neurobiology and Immunology (1971)
Research
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Research Projects
ORCID
0000-0002-3490-1259
Research at a Glance
Yale Co-Authors
Publications Timeline
Hal Blumenfeld, MD, PhD
Jeffery Kocsis, PhD
Jong M. Rho, MD
Kaya Bilguvar, MD, PhD
Michael DiLuna, MD, FAANS
Ognen Petroff, MD, FAAN (Neurology), FACNS, FAES, FANA
Publications
2026
Redox regulation of neuroinflammatory pathways contributes to damage in Alzheimer’s disease brain
Carnevale L, Banerjee P, Zhang X, Navarro J, Raspur C, Patel P, Nakamura T, Schahrer E, Scott H, Lang N, Diedrich J, Roberts A, Yates J, Lipton S. Redox regulation of neuroinflammatory pathways contributes to damage in Alzheimer’s disease brain. Cell Chemical Biology 2026 PMID: 42030932, DOI: 10.1016/j.chembiol.2026.03.017.Peer-Reviewed Original ResearchAltmetricConceptsRedox regulationStimulator of interferon genesAlzheimer's diseaseDiseased brainS-nitrosylationRedox-based posttranslational modificationAberrant activationActivation of innate immune signalingAlzheimer's disease brainTransgenic AD mouse modelRedox-sensitive cysteinesAD mouse modelInnate immune signalingProtein S-nitrosylationType I Interferon SignalingPosttranslational modificationsRegulation of neuroinflammatory pathwaysI interferon signalingImmune signalingMolecular linkProtein aggregationSynaptic lossHuman ADInnate immunityAge-related neurological disordersAberrant Protein S‐Nitrosylation Mimics the Effect of Rare Genetic Mutations in Neurodegenerative Diseases
Wang Y, Lipton S. Aberrant Protein S‐Nitrosylation Mimics the Effect of Rare Genetic Mutations in Neurodegenerative Diseases. Journal Of Neurochemistry 2026, 170: e70365-e70365. PMID: 41635116, PMCID: PMC12981794, DOI: 10.1111/jnc.70365.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGenome wide association studiesPost-translational modificationsAberrant S-nitrosylationRare genetic mutationsS-nitrosylationGenetic mutationsPost-translational modification of proteinsAlzheimer's diseaseAmyotrophic lateral sclerosis/frontotemporal dementiaDiseased brainS-nitrosylated proteinsModification of proteinsProtein S-nitrosylationGenetic risk factorsAssociation studiesProtein functionEnvironmental factorsRisk gene variantsHuman geneticsProteomic analysisEnvironmental stressSynaptic dysfunctionRedox biologyGene variantsFunctional consequencesAutophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC‐Derived Cortical Organoids
Labra S, Compher J, Prabhavalkar A, Almaraz M, Kwong C, Baal C, Talantova M, Dolatabadi N, Piña‐Sanz J, Wang Y, Yoon L, Ghatak S, Gao Z, Zhang Y, Trudler D, Massey L, Lin W, Balistreri A, Bula M, Schork N, Mondala T, Head S, Kelly J, Lipton S. Autophagy Activators Normalize Aberrant Tau Proteostasis and Rescue Synapses in Human Familial Alzheimer's Disease iPSC‐Derived Cortical Organoids. Advanced Science 2026, 13: e14783. PMID: 41591759, PMCID: PMC13042409, DOI: 10.1002/advs.202514783.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsSingle-cell RNA sequencing analysisAlzheimer's diseaseFamilial AD mutationsAD patient brainsIsogenic wild-typeP-tau accumulationHigh-molecular-weightMonomeric tauTau proteostasisAD mutationsCause of dementiaAD pathogenesisAmyloid-betaAD phenotypeSynapse lossAnalysis of ADSynaptic lossMolecular mechanismsWild-typePatient's brainPluripotent stem cellsAutophagy activationMolecular abnormalitiesDisease modelsAccumulation
2025
Alzheimer's Disease Pathogenesis Perturbs Specific Spatial Protein Isoforms
McClatchy D, Labra S, Baal C, Lipton S, Yates J. Alzheimer's Disease Pathogenesis Perturbs Specific Spatial Protein Isoforms. Alzheimer's & Dementia 2025, 21: e103003. PMCID: PMC12728306, DOI: 10.1002/alz70855_103003.Peer-Reviewed Original ResearchConceptsUnique subcellular compartmentsIdentical proteinsSubcellular compartmentsAlzheimer's diseaseReciprocal expression patternProtein degradation rateBiological processesUnbiased mass spectrometryProcess of vesicle transportNucleo-cytoplasmic traffickingPulse-chase strategyAD mouse modelVesicle transportProtein traffickingProtein mislocalizationAD pathogenesisProtein isoformsUnique proteinsHuman brain samplesQuantitative MSProtein identificationQuantitative MS analysisBiological fractionationAD organoidsDruggable pathwaysProteome-wide profiling of S-nitrosylated proteins using the SNOTRAP probe and mass spectrometry-based detection
Yang H, Amal H, Tannenbaum S, Lipton S. Proteome-wide profiling of S-nitrosylated proteins using the SNOTRAP probe and mass spectrometry-based detection. Nature Protocols 2025, 1-26. PMID: 41258014, PMCID: PMC13004284, DOI: 10.1038/s41596-025-01282-1.Peer-Reviewed Original ResearchCitationsAltmetricConceptsProteome-wide profilingS-nitrosylated proteinsProtein S-nitrosylationS-nitrosylationIn situ labelingSample preparationSNO-proteinsProteome-wide approachMS-based identificationPost-translational modificationsCellular signal transductionMass spectrometry-based detectionTissue sample preparationOrbitrap MSMS measurementsS-nitrosylation reactionLabel-free quantificationS-nitrosoproteomeStreptavidin captureProtein stabilitySignal transductionArgon atmosphereDisease-modifying therapeuticsMouse tissuesLow abundanceThe transcriptional and cellular landscape of cognitive resilience to Alzheimer’s disease
Khera N, Raju R, Lipton S. The transcriptional and cellular landscape of cognitive resilience to Alzheimer’s disease. Frontiers In Molecular Neuroscience 2025, 18: 1665802. PMID: 41293128, PMCID: PMC12640947, DOI: 10.3389/fnmol.2025.1665802.Peer-Reviewed Original ResearchCitationsAltmetricConceptsAlzheimer's diseasePathological features of Alzheimer's diseaseCellular landscapeNon-cell autonomous effectsFeatures of Alzheimer's diseaseAD-related dementiaMisfolded protein accumulationCell typesTranscriptional changesProtein accumulationTranscriptional driversGene expressionSynaptic stabilityCognitive resilienceCognitive functionDrug developmentCellsPreserving cognitive functionGenesCognitive healthAlzheimerPatient's capacityGasotransmitter signaling in the brain: New frontiers for therapeutics
Paul B, Ignarro L, Lipton S. Gasotransmitter signaling in the brain: New frontiers for therapeutics. Neurotherapeutics 2025, 22: e00784. PMID: 41188152, PMCID: PMC12664559, DOI: 10.1016/j.neurot.2025.e00784.Peer-Reviewed Original ResearchCitationsClassically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide
John S, Seim G, Erazo-Flores B, Votava J, Urquiza U, Arp N, Steill J, Freeman J, Carnevale L, Roberts I, Qing X, Lipton S, Stewart R, Knoll L, Fan J. Classically activated macrophages undergo functionally significant nucleotide metabolism remodelling driven by nitric oxide. Nature Metabolism 2025, 7: 1681-1702. PMID: 40759751, PMCID: PMC12356500, DOI: 10.1038/s42255-025-01337-3.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsDe novo synthesisNucleotide metabolismDynamic reprogrammingTranscriptional downregulationRegulation of nucleotide metabolismDe novo synthesis of purinesPurine salvageDe novo synthesis of pyrimidinesSynthesis of purinesIntracellular parasite Toxoplasma gondiiSynthesis of pyrimidinesRegulatory mechanismsCytidine triphosphateMetabolic remodelingNucleotideUridine monophosphateFunctional significanceParasite Toxoplasma gondiiMetabolismNitric oxidePurinePurine basesMacrophage migrationImmune responseActivated macrophagesAberrant S-nitrosylation in the TCA cycle contributes to mitochondrial dysfunction, energy compromise, and synapse loss in neurodegenerative diseases
Nakamura T, Sharma A, Lipton S. Aberrant S-nitrosylation in the TCA cycle contributes to mitochondrial dysfunction, energy compromise, and synapse loss in neurodegenerative diseases. Neurotherapeutics 2025, 22: e00708. PMID: 40730758, PMCID: PMC12664530, DOI: 10.1016/j.neurot.2025.e00708.Peer-Reviewed Original ResearchCitationsConceptsPosttranslational modificationsMitochondrial energy productionMitochondrial dysfunctionS-nitrosylationMitochondrial metabolismSynapse lossTricarboxylic acid cycle enzymesElectron transport chain proteinsAberrant posttranslational modificationsAberrant S-nitrosylationNeurodegenerative diseasesS-nitrosylation of cysteine residuesMitochondrial bioenergetic functionProtein S-nitrosylationA-ketoglutarate dehydrogenaseMitochondrial dynamicsNitro-oxidative stressTCA cycleModels of neurodegenerative diseasesCycle enzymesBioenergetic functionCysteine residuesChain proteinSynaptic degenerationA-ketoglutarateRedox modulation of the complement cascade contributes to synapse loss in Alzheimer's disease
Oh C, Wang Y, Lipton S. Redox modulation of the complement cascade contributes to synapse loss in Alzheimer's disease. Neurotherapeutics 2025, 22: e00707. PMID: 40713246, PMCID: PMC12664466, DOI: 10.1016/j.neurot.2025.e00707.Peer-Reviewed Original ResearchCitationsConceptsAberrant S-nitrosylationAlzheimer's diseaseRedox-mediated posttranslational modificationSynaptic lossNitric oxide (NO)-related speciesReactive nitrogen speciesPhagocytosis of synapsesProgression of ADCorrelated to cognitive declineComplement systemPosttranslational modificationsInnate immune systemSenile plaquesSynapse lossS-nitrosylationDying CellsImmune responseRedox modulationComplement cascadeSpeciesCentral nervous systemComplement proteinsNitrosative stressComplementAlzheimer
Academic Achievements & Community Involvement
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Activities
activity American Academy of Neurology
07/01/2000 - PresentProfessional OrganizationsMemberDetailsFellowactivity American Neurological Association
11/01/1987 - PresentProfessional OrganizationsMemberDetailsElected Fellowactivity Society for Neuroscience
10/09/2000 - 11/07/2008CommitteesMemberDetailsChair of Education Committee and Neurobiology of Disease Workshops
Honors
honor NIH Director's Grant Award
04/01/2016National AwardNational Institutes of Health/NIDADetailsUnited Stateshonor Elected Fellow, American Association for the Advancement of Science
09/09/2011National AwardAAAS, Neuroscience sectionDetailsUnited Stateshonor Ernst Jung Prize in Medicine
05/08/2004International AwardErnst Jung FoundationDetailsGermanyhonor Alpha Omega Alpha
06/04/1974National AwardDetailsUnited Stateshonor Phi Beta Kappa
06/10/1971National AwardDetailsUnited States
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