Sidharth Tyagi, PhD
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Biography
Sidharth Tyagi, PhD is an MD-PhD candidate at the Yale School of Medicine whose research focuses on the molecular and cellular mechanisms of pain, with a particular emphasis on voltage-gated sodium channels as therapeutic targets.
Before coming to Yale, Dr. Tyagi trained at the University of Colorado, where he investigated the role of voltage-gated calcium channels in ALS and other neurodegenerative diseases.
At Yale, he pursued PhD training with Stephen Waxman, MD, PhD, and has led projects defining sodium channel architecture in sensory neurons, the regulation of nociceptor excitability by inflammation, and the development of scalable tools for ion channel drug discovery, including high-throughput electrophysiology (Cell Reports Methods, Nature Protocols) and real-time imaging of membrane protein dynamics (Nature Protocols, cover article). His research has yielded more than 25 publications, including work in Cell Reports, PNAS, and Nature Reviews Neuroscience.
A principal outcome of his PhD research is UbiquiNav, a selective degrader of the Nav1.8 channel that reduces sensory neuron excitability and demonstrates analgesic efficacy in vivo. This project, supported by an NIH F31 fellowship, is the subject of a U.S. patent and ongoing translational development, bridging basic neuroscience and drug discovery.
Dr. Tyagi’s research integrates ion channel biology, high-throughput screening, and translational neuroscience to advance non-addictive pain therapeutics.
Departments & Organizations
Education & Training
- PhD
- Yale University, Neuroscience
- MS
- University of Colorado, Boulder, Integrative Physiology (2019)
- BA
- University of Colorado, Boulder, Biochemistry, Integrative Physiology (2017)
Research
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Overview
Medical Research Interests
ORCID
0000-0001-6097-0541
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Stephen Waxman, MD, PhD
Sulayman Dib-Hajj, PhD
Mohammad-Reza Ghovanloo, PhD
Peng Zhao, PhD
Shujun Liu
Philip Effraim, MD, PhD
Ion Channels
Publications
2025
Altered Gating of Two CaV2.1 Variants Linked to Neurodevelopmental Disorders With Epilepsy and Migraine
Meza U, Romero‐Méndez C, León D, Bibollet H, Tyagi S, Bhadane P, Papadopoulos S, Salamanca‐Vera M, Perez‐Aguilar J, Wangler M, Bannister R. Altered Gating of Two CaV2.1 Variants Linked to Neurodevelopmental Disorders With Epilepsy and Migraine. The FASEB Journal 2025, 39: e71012. PMID: 40906262, DOI: 10.1096/fj.202501708r.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsFamilial hemiplegic migraine type 1Episodic ataxia type 2Channel functionGain-of-functionChannel gatingChannel activation kineticsPatch-clamp electrophysiologyGlobal developmental delayHEK-293 cellsSpectrum of neurological disordersRelease of neurotransmittersP/Q-typeGenome-wide sequencingCerebellar atrophyDelayed closureRat variantNonsense mutationDevelopmental delayType 1Central synapsesType 2Activation kineticsChannel complexPathological mutationsRat orthologueEnhanced trafficking of an inherited erythromelalgia NaV1.7 mutant channel at a physiological temperature
Mis M, Tyagi S, Akin E, Ghovanloo M, Zhao P, Dib-Hajj F, Randall A, Waxman S, Dib-Hajj S. Enhanced trafficking of an inherited erythromelalgia NaV1.7 mutant channel at a physiological temperature. Neurobiology Of Pain 2025, 18: 100188. PMID: 40606587, PMCID: PMC12221430, DOI: 10.1016/j.ynpai.2025.100188.Peer-Reviewed Original ResearchConceptsMutant channelsIB4- neuronsInherited ErythromelalgiaEnhanced traffickingActivity of Nav1.7Expressed sodium channelsHuman pain disordersCurrent-clamp recordingsDRG sensory neuronsVoltage-clamp recordingsAttacks of burning painGain-of-function mutationsIncreased membrane insertionHyperpolarizing shiftNeuronal hyperexcitabilityPain disordersCurrent-clampNav1.7 channelsWT channelsSensory neuronsSodium channelsIncreased firingTemporary reliefNeuronsSkin temperatureHigh-throughput multiplex voltage-clamp/current-clamp evaluation of acutely isolated neurons
Ghovanloo M, Tyagi S, Zhao P, Kiziltug E, Estacion M, Effraim P, Dib-Hajj S, Waxman S. High-throughput multiplex voltage-clamp/current-clamp evaluation of acutely isolated neurons. Nature Protocols 2025, 1-26. PMID: 40514421, DOI: 10.1038/s41596-025-01194-0.Peer-Reviewed Original ResearchAltmetricConceptsPatch-clamp techniquePatch-clamp methodPatch-clamp approachPatch-clamp experimentsHeterologous cell linesIsolated neuronsInvestigated receptorsGraphical user interfaceIsolation of neuronsCell preparationsExcitable cellsOpen-source softwareCell linesNeuronsFiltration criteriaIndividual neuronsUser interfaceNative stateDrug screeningRobotic systemDrug developmentManual implementationBiophysical equationsComplex datasetsIntact tissueSculpting excitable membranes: voltage-gated ion channel delivery and distribution
Tyagi S, Higerd-Rusli G, Akin E, Waxman S, Dib-Hajj S. Sculpting excitable membranes: voltage-gated ion channel delivery and distribution. Nature Reviews Neuroscience 2025, 26: 313-332. PMID: 40175736, DOI: 10.1038/s41583-025-00917-2.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNeuronal compartmentsPeripheral nervous system neuronsIon channel localizationNervous system neuronsMembrane ion channelsIon channel traffickingChronic painNeuronal excitabilityPotential therapeutic targetChannel traffickingIon channel distributionSystem neuronsChannel localizationNeuronal activityTherapeutic targetIon channelsTarget membrane insertionPost-translational modificationsDistal neuronal compartmentsDisease statesNeuronal homeostasisVesicular sortingDiseaseSpatiotemporal regulationChannel deliveryIn vitro inhibition of voltage-dependent sodium currents by the antifungal drug amorolfine
Ghovanloo M, Tyagi S, Effraim P, Waxman S. In vitro inhibition of voltage-dependent sodium currents by the antifungal drug amorolfine. Journal Of Biological Chemistry 2025, 301: 108407. PMID: 40090585, PMCID: PMC12004706, DOI: 10.1016/j.jbc.2025.108407.Peer-Reviewed Original ResearchCitationsAltmetricConceptsNav channelsInhibition of voltage-dependent sodium currentsLocal anestheticsVoltage-dependent sodium currentsStabilization of inactivationVoltage-gated sodiumSodium currentChannel inactivationChannel inhibitorsAmorolfineInactivated statePharmacological modulationIn vitro inhibitionIon channelsInhibitorsNavNav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids
Ghovanloo M, Tyagi S, Zhao P, Waxman S. Nav1.8, an analgesic target for nonpsychotomimetic phytocannabinoids. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2416886122. PMID: 39835903, PMCID: PMC11789019, DOI: 10.1073/pnas.2416886122.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsExcitation of peripheral sensory neuronsTherapeutic potential of cannabinoidsPotential of cannabinoidsPeripheral sensory neuronsVoltage-gated sodiumSpectrum of adverse effectsNociceptor excitabilityPain signalsIn vivo studiesAnalgesic targetsPain treatmentAttenuate painRepetitive firingNav1.8Sensory neuronsTreatment optionsClinical studiesInhibit excitabilityAnalgesic compoundsPainTherapeutic potentialCannabigerolProof-of-principalAdverse effectsTreatment
2024
TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons
Ghovanloo M, Effraim P, Tyagi S, Aldrich A, Cheng X, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. TRPM8 Mutations Associated With Persistent Pain After Surgical Injury of Corneal Trigeminal Axons. Neurology Genetics 2024, 10: e200206. PMID: 39555137, PMCID: PMC11567650, DOI: 10.1212/nxg.0000000000200206.Peer-Reviewed Original ResearchCitationsAltmetricConceptsLaser-assisted in situ keratomileusisPostoperative ocular painTrigeminal ganglion neuronsOcular painMultielectrode array recordingsPersistent painGanglion neuronsLaser-assisted in situ keratomileusis surgeryAxonal injuryRat trigeminal ganglion neuronsTransient receptor potential cation channelCorneal refractive surgeryMultielectrode arraysAnalysis of patientsPatch-clamp analysisGenomic analysis of patientsWild-typePatch-clamp resultsExposure to mentholRefractive surgeryHyperpolarizing directionNeuronal hyperexcitabilityPain-freeTrigeminal axonsWT channelsFinancial Compensation of Academic Otolaryngologists in the United States: Trends and Distribution
Shah R, Tyagi S, Futela D, Malhotra A, Judson B. Financial Compensation of Academic Otolaryngologists in the United States: Trends and Distribution. The Laryngoscope 2024, 135: 1367-1371. PMID: 39530275, DOI: 10.1002/lary.31909.Peer-Reviewed Original ResearchCitationsAltmetricConceptsSalary survey dataMedian compensationFinancial compensationAcademic medical centerCompensation dataFaculty compensationSalary surveySalary gapSalary inequitiesSurvey dataMedical CenterFaculty membersSenior ranksAcademic otolaryngology departmentUnited StatesUS academic centersGeographic regionsFinancialFull-time facultyCompensationImpacts of resident physician unionization on house staff compensation
Tyagi S, Shah R, Huttler J, Kayani J, Ghovanloo M, Effraim P. Impacts of resident physician unionization on house staff compensation. PLOS ONE 2024, 19: e0308100. PMID: 39361626, PMCID: PMC11449312, DOI: 10.1371/journal.pone.0308100.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNon-union counterpartsPhysician unionsWorking long hoursUnion statusResidency training programsUnion programCost-of-livingLow wagesStaff compensationLong hoursTraining programSalaryInternal medicine residency training programsPhysicians-in-trainingRegional factorsDisbursementBenefit dataCross-sectional investigationMonetary benefitsUnionResident salariesCompensationCost-of-living differencesPGY-1Residency programsReal-time imaging of axonal membrane protein life cycles
Tyagi S, Higerd-Rusli G, Akin E, Baker C, Liu S, Dib-Hajj F, Waxman S, Dib-Hajj S. Real-time imaging of axonal membrane protein life cycles. Nature Protocols 2024, 19: 2771-2802. PMID: 38831222, PMCID: PMC11721981, DOI: 10.1038/s41596-024-00997-x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricConceptsMembrane proteinsRecycling of membrane proteinsProtein subcellular localizationMembrane protein homeostasisMembrane protein traffickingEngineered membrane proteinsMultiple membrane proteinsSelf-labeling tagsCell culturesProtein traffickingProtein tagsSubcellular localizationProtein homeostasisSpatiotemporal regulationCellular processesMultiple proteinsSubcellular distributionVesicular packagingThroughput mannerProteinNeuronal compartmentsDistal axonsProtein spatial organizationFluorescent labelingNeuronal cultures
Academic Achievements & Community Involvement
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Honors
honor Prize Teaching Fellowship
04/28/2023Yale University AwardGraduate School of Arts and SciencesDetailsUnited States
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