Sidharth Tyagi, MD, PhD
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Biography
Sidharth Tyagi, MD, PhD conducts research 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 30 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
- MD
- Yale School of Medicine, Medicine (2026)
- 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
Philip Effraim, MD, PhD
Shujun Liu
Ion Channels
Publications
Featured Publications
Sculpting 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, PMCID: PMC12828907, 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 deliveryNav1.8, 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 effectsTreatmentReal-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 culturesCompartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α
Tyagi S, Higerd-Rusli G, Ghovanloo M, Dib-Hajj F, Zhao P, Liu S, Kim D, Shim J, Park K, Waxman S, Choi J, Dib-Hajj S. Compartment-specific regulation of NaV1.7 in sensory neurons after acute exposure to TNF-α. Cell Reports 2024, 43: 113685. PMID: 38261513, PMCID: PMC10947185, DOI: 10.1016/j.celrep.2024.113685.Peer-Reviewed Original ResearchCitationsAltmetricConceptsTNF-aSensory neuronsEffect of TNF-aSensory neuron excitabilityTumor necrosis factor-aRegulation of NaV1.7Voltage-gated sodiumPro-inflammatory cytokinesCompartment-specific effectsNeuronal plasma membraneSensitize nociceptorsNeuronal excitabilitySomatic membraneChannel N terminusElectrophysiological recordingsP38 MAPKIon channelsFactor AAcute exposureMolecular determinantsNeuronsAxonal endingsPhospho-acceptor sitesPlasma membraneCompartment-specific regulationInflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity
Higerd-Rusli G, Tyagi S, Baker C, Liu S, Dib-Hajj F, Dib-Hajj S, Waxman S. Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2215417120. PMID: 36897973, PMCID: PMC10089179, DOI: 10.1073/pnas.2215417120.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsCell biological mechanismsAxonal surfaceLive-cell imagingIon channel traffickingAnterograde transport vesiclesTransport vesiclesInflammatory mediatorsChannel traffickingPlasma membraneVesicular loadingIon channelsKv channelsPotential therapeutic targetPotassium channel KSodium channel NaTraffickingBiological mechanismsTherapeutic targetAbundanceRetrograde transportDistal axonsChannel NaInflammatory painNociceptor activityAxonal transport
2026
Nav1.8 Variant I206M as a Latent Susceptibility Factor in Postaxotomy Ocular Pain
Ghovanloo M, Effraim P, Tyagi S, Aldrich A, Yuan J, Schulman B, Jacobs D, Dib-Hajj S, Waxman S. Nav1.8 Variant I206M as a Latent Susceptibility Factor in Postaxotomy Ocular Pain. Neurology Genetics 2026, 12: e200367. PMID: 41868096, PMCID: PMC13004580, DOI: 10.1212/nxg.0000000000200367.Peer-Reviewed Original ResearchCitationsAltmetricConceptsPersistent ocular painCorneal refractive surgeryOcular painTrigeminal neuronsRefractive surgerySusceptibility factorsChronic ocular painHuman pain disordersTrigeminal ganglia neuronsRat trigeminal neuronsClinical validationCohort of patientsPatch-clamp electrophysiologyMultielectrode array recordingsWhole-exome sequencingIon channel variantsPersistent painPain disordersAnalgesic targetsNerve injuryTrigeminal axonsGanglia neuronsDistal axonsChannel variantsNav1.8Cost-Effectiveness of Free Tissue Transfer for Unilateral Facial Paralysis.
Shah R, Tyagi S, Munshi M, Gadkaree S, Lee Y, Mohan S. Cost-Effectiveness of Free Tissue Transfer for Unilateral Facial Paralysis. Facial Plastic Surgery & Aesthetic Medicine 2026, 26893614261429298. PMID: 41778390, DOI: 10.1177/26893614261429298.Peer-Reviewed Original ResearchConceptsUnilateral facial paralysisFree tissue transferQuality-adjusted life yearsFacial paralysisSuccess rateTissue transferFree tissue transfer surgerySuccess rate of free tissue transferIncremental cost-effectiveness ratioFree tissue transfer techniquesTissue transfer surgeryCost-effectiveness ratioTissue transfer techniquesChronic facial paralysisCost-effective treatmentCost-effectiveSurgical pathwayTransfer surgeryLife yearsSurgeryParalysisPublished literatureInterventionTreatmentUtility values
2025
ImmunoStruct enables multimodal deep learning for immunogenicity prediction
Givechian K, Rocha J, Liu C, Yang E, Tyagi S, Greene K, Ying R, Caron E, Iwasaki A, Krishnaswamy S. ImmunoStruct enables multimodal deep learning for immunogenicity prediction. Nature Machine Intelligence 2025, 8: 70-83. DOI: 10.1038/s42256-025-01163-y.Peer-Reviewed Original ResearchCitationsAltmetricSelective targeting of voltage-gated sodium channels to achieve analgesia: current status and future directions
Gordon E, Tyagi S, Dib-Hajj S, Bennett D. Selective targeting of voltage-gated sodium channels to achieve analgesia: current status and future directions. Pain 2025, 166: s42-s46. PMID: 41086326, DOI: 10.1097/j.pain.0000000000003639.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsVoltage-gated sodium channelsSodium channelsAnalgesic drug targetsSubtype-specific antibodiesSubtype-specific mannerTargeted analgesicPain disordersAcute painChannel blockersNaV isoformsAction potentialsNav subtypesExcitable cellsNociceptorsPainAnalgesicChannel conductanceDrug targetsNavNav1.8Human genetic dataBlockersAnalgesiaSubtypesEffects of stapes surgery prosthesis type on hearing outcome, post-operative dizziness and benzodiazepine use
Wilkins S, Shah R, Valdez C, Malik D, Tyagi S, Hildrew D, Schwartz N. Effects of stapes surgery prosthesis type on hearing outcome, post-operative dizziness and benzodiazepine use. The Journal Of Laryngology And Otology 2025, 139: 1196-1201. PMID: 41030100, PMCID: PMC12674984, DOI: 10.1017/s0022215125103575.Peer-Reviewed Original ResearchMeSH Keywords and ConceptsConceptsPost-operative dizzinessAir-bone gap closureHearing outcomesOtosclerosis surgeryStapedotomy patientsSpeech reception thresholdSensorineural hearing lossReception thresholdsHearing lossProsthesis typeRecords of patientsDizzy patientsLarger improvementsGap closureBenzodiazepine useStapedotomyComplication rateNo significant differenceSurgical approachSurgical methodsDizzinessOvernight admissionOtosclerosisStapedectomyPatients
Academic Achievements & Community Involvement
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Featured
honor Prize Teaching Fellowship
04/28/2023Yale University AwardGraduate School of Arts and SciencesDetailsUnited States
Honors
honor Selma and Karl Folkers Prize in Biomedical Research
05/18/2026Yale School of Medicine AwardYale UniversityDetailsUnited States
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