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
Philip Effraim, MD, PhD
Shujun Liu
Ion Channels
Publications
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 admissionOtosclerosisStapedectomyPatientsAltered 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 ResearchAltmetricMeSH 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, 21: 609-634. PMID: 40514421, PMCID: PMC13037423, 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, 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 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 channelsInhibitorsNav
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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