Zachary Levine, PhD
Cards
About
Titles
Assistant Professor Adjunct
Biography
Zachary Levine is an Assistant Professor Adjunct of Pathology at Yale School of Medicine. While trained in computational biophysics with special emphasis in protein folding, his interests have recently expanded into solution biophysics measurements of soluble amyloid oligomers. Many of his projects combine atomistic molecular dynamics (MD) simulations with single-molecule fluorescence techniques (smFRET, FCS, and anisotropy) in order to deduce the physical and thermodynamic determinants of age-related diseases.
Appointments
Pathology
Assistant Professor AdjunctPrimary
Other Departments & Organizations
Education & Training
- Postdoctoral Training
- University of California Santa Barbara (2017)
- PhD
- University of Southern California, Physics (2013)
- MSc
- University of Southern California, Computer Science (2012)
- MA
- University of Southern California, Physics (2008)
- BS
- San Francisco State University, Physics (2006)
Research
Publications
2024
Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology
Miller B, Kim S, Cao K, Mehta H, Thumaty N, Kumagai H, Iida T, McGill C, Pike C, Nurmakova K, Levine Z, Sullivan P, Yen K, Ertekin‐Taner N, Atzmon G, Barzilai N, Cohen P. Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4‐induced brain pathology. Aging Cell 2024, e14153. PMID: 38520065, DOI: 10.1111/acel.14153.Peer-Reviewed Original ResearchAPOE4 carriersAPOE4 alleleAmyloid beta clearanceMouse model of amyloidosisAlzheimer's diseaseAmyloid-beta pathologyIn silico analysisAmyloid-beta accumulationMitochondrial-derived peptideGenes associated with phagocytosisResistance to ADModel of amyloidosisAmyloid-betaBeta pathologyAssociated with longevitySilico analysisHumaninFactors to Alzheimer's diseaseApoE4Transcriptomic assessmentAmino acidsInfluence longevityAllelesPhagocytosisAshkenazi descentDecoupling sequence and conformational determinants of strong IDP binders to inform therapeutic intervention
Bogin B, Levine Z. Decoupling sequence and conformational determinants of strong IDP binders to inform therapeutic intervention. Biophysical Journal 2024, 123: 74a. DOI: 10.1016/j.bpj.2023.11.520.Peer-Reviewed Original Research
2023
Apolipoprotein E polymorphism‐dependent effects on cellular function
Beyer B, Levine Z. Apolipoprotein E polymorphism‐dependent effects on cellular function. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.077424.Peer-Reviewed Original ResearchApolipoprotein EStructure:function relationshipsCombination of cell-basedIsogenic hiPSC linesTransport of lipidsSubcellular localizationE4 isoformCellular functionsFunction of apolipoprotein EBiophysical approachesLiving cellsTransport of E2Cell typesCo-localizationCentral nervous systemLipoprotein particlesIsoformsHuman astrocytesRelationship of apolipoprotein EHiPSC linesCell-basedInvestigate mechanismsApolipoproteinCellsOrganellesComparing the structure and stability of diverse amyloid beta oligomers using fluorescence correlation spectroscopy
Nurmakova K, Levine Z. Comparing the structure and stability of diverse amyloid beta oligomers using fluorescence correlation spectroscopy. Biophysical Journal 2023, 122: 350a. DOI: 10.1016/j.bpj.2022.11.1944.Peer-Reviewed Original Research
2019
The Mitochondrial Peptide Humanin Targets but Does Not Denature Amyloid Oligomers in Type II Diabetes
Levine ZA, Teranishi K, Okada AK, Langen R, Shea JE. The Mitochondrial Peptide Humanin Targets but Does Not Denature Amyloid Oligomers in Type II Diabetes. Journal Of The American Chemical Society 2019, 141: 14168-14179. PMID: 31456396, DOI: 10.1021/jacs.9b04995.Peer-Reviewed Original Research
2018
A threonine zipper that mediates protein–protein interactions: Structure and prediction
Oi C, Treado JD, Levine ZA, Lim CS, Knecht KM, Xiong Y, O'Hern CS, Regan L. A threonine zipper that mediates protein–protein interactions: Structure and prediction. Protein Science 2018, 27: 1969-1977. PMID: 30198622, PMCID: PMC6201716, DOI: 10.1002/pro.3505.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsProtein-protein interfacesZipper structureBeta-barrel proteinsIntermonomer hydrogen bondsBarrel proteinsThr residueSide-chain dihedral anglesBiotechnological applicationsProtein interfacesMolecular dynamics simulationsDihedral angleSide-chain conformationsThrH-bondingHydrogen bondsChain conformationMD simulationsSteric constraintsDrug discoveryDynamics simulationsResiduesTargeting the Intrinsically Disordered Proteome Using Small-Molecule Ligands
Wójcik S, Birol M, Rhoades E, Miranker AD, Levine ZA. Targeting the Intrinsically Disordered Proteome Using Small-Molecule Ligands. Methods In Enzymology 2018, 611: 703-734. PMID: 30471705, DOI: 10.1016/bs.mie.2018.09.036.Peer-Reviewed Original ResearchConceptsSmall molecule manipulationSingle-molecule techniquesProtein ensemblesPathological functionsMolecule ligandsTractable targetsConformational flexibilityProteomeAttractive targetProteinDrug developmentExperimental approachIDPsTargetLigandsComplimentary partnersConformationBioengineeringWide range
2017
Significant Performance Enhancement of Polymer Resins by Bioinspired Dynamic Bonding
Seo S, Lee DW, Ahn JS, Cunha K, Filippidi E, Ju SW, Shin E, Kim B, Levine ZA, Lins RD, Israelachvili JN, Waite JH, Valentine MT, Shea JE, Ahn BK. Significant Performance Enhancement of Polymer Resins by Bioinspired Dynamic Bonding. Advanced Materials 2017, 29 PMID: 28833661, PMCID: PMC5640498, DOI: 10.1002/adma.201703026.Peer-Reviewed Original ResearchMineral surfacesMussel foot proteinsMolecular dynamics simulationsMetal coordinationPolymer networksPolymeric interfacesPriming layerLoad-bearing materialsCatechol groupsDynamic bondingPolymer resinDynamics simulationsFoot proteinsHydrophobic bondsToughness enhancementAdhesion strengthAdhesive primerBondingSignificant performance enhancementSecondary surfacePerformance enhancementOrders of magnitudeSurfaceResinBondsQuantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations
Sözer EB, Levine ZA, Vernier PT. Quantitative Limits on Small Molecule Transport via the Electropermeome — Measuring and Modeling Single Nanosecond Perturbations. Scientific Reports 2017, 7: 57. PMID: 28246401, PMCID: PMC5428338, DOI: 10.1038/s41598-017-00092-0.Peer-Reviewed Original Research
2016
Surface force measurements and simulations of mussel-derived peptide adhesives on wet organic surfaces
Levine ZA, Rapp MV, Wei W, Mullen RG, Wu C, Zerze GH, Mittal J, Waite JH, Israelachvili JN, Shea JE. Surface force measurements and simulations of mussel-derived peptide adhesives on wet organic surfaces. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 4332-4337. PMID: 27036002, PMCID: PMC4843488, DOI: 10.1073/pnas.1603065113.Peer-Reviewed Original ResearchConceptsSelf-assembled monolayersOrganic surfacesHydrophobic self-assembled monolayersReplica exchange molecular dynamics simulationsSurface force measurementsMolecular interactionsFree energy profilesMussel foot proteinsUmbrella sampling simulationsMolecular dynamics simulationsVan der WaalsPeptide adsorptionPeptide adhesionSFA measurementsUnderwater adhesivesAqueous adhesivesDer WaalsSurface forcesDynamics simulationsElectrostatic forcesFoot proteinsProtein analoguesSpecific interactionsAdsorptionAdhesive properties
Academic Achievements and Community Involvement
Links & Media
Media
The Mitochondrial Peptide Humanin Targets, But Does Not Denature Amyloid Oligomers in Type II Diabetes
Cover art from our lab was featured in the Sept. 11th, 2019 issue of the Journal of the American Chemical Society (JACS). "The small, mitochondrial peptide humanin binds to amyloid oligomers in Type II Diabetes, acting as an endogenous amyloid chaperone that regulates fibril growth. Outside of their native environments, mitochondrial peptides exhibit a remarkable potential for targeting intermediate protein oligomers in the cytosol and inhibiting cytotoxicity across multiple amyloid diseases."