Voluntary Faculty
Voluntary faculty are typically clinicians or others who are employed outside of the School but make significant contributions to department programs at the medical center or at affiliate institutions.
Voluntary rank detailsRichard Silverman, MD
Assistant Clinical ProfessorAbout
Research
Publications
2025
Kinetically Controlled aza-Michael/Epimerization Cascade Enables a Scalable Total Synthesis of Putative (+)‑Fumigaclavine F
Dukes A, Weerawarna P, Silverman R. Kinetically Controlled aza-Michael/Epimerization Cascade Enables a Scalable Total Synthesis of Putative (+)‑Fumigaclavine F. Organic Letters 2025, 27: 10174-10179. PMID: 40864606, PMCID: PMC12459949, DOI: 10.1021/acs.orglett.5c03284.Peer-Reviewed Original ResearchTargeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors
Patel A, Tong S, Lozada K, Awasthi A, Silverman R, Totonchy J, Yang S. Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors. Pharmaceutics 2025, 17: 691. PMID: 40574005, PMCID: PMC12196278, DOI: 10.3390/pharmaceutics17060691.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsNeuronal nitric oxide synthaseNeuronal nitric oxide synthase inhibitorActivity of immune checkpoint inhibitorsT cell activationImmune checkpoint inhibitorsAnti-melanoma activityT cellsTargeting nNOSNitric oxide synthaseCheckpoint inhibitorsIFN-gCD8+ PD-1+ T cellsInterleukin-2PD-1+ T cellsEffects of nNOS inhibitionIL-2-secreting T cellsImmune responseMouse peripheral blood mononuclear cellsOxide synthaseAnti-PD-1Immune checkpoint blockadeMelanoma immune responsePD-1 blockadePD-L1 expressionTruncated pyridinylbenzylamines: Potent, selective, and highly membrane permeable inhibitors of human neuronal nitric oxide synthase
Vasu D, Do H, Li H, Hardy C, Poulos T, Silverman R. Truncated pyridinylbenzylamines: Potent, selective, and highly membrane permeable inhibitors of human neuronal nitric oxide synthase. Bioorganic & Medicinal Chemistry 2025, 124: 118193. PMID: 40252563, PMCID: PMC12404148, DOI: 10.1016/j.bmc.2025.118193.Peer-Reviewed Original ResearchConceptsHuman neuronal nitric oxide synthaseArtificial membrane permeability assayMembrane permeability assayMembrane permeable inhibitorCrystal structureSuzuki-Miyaura cross-coupling reactionTetra-n-butylammonium fluorideCross-coupling reactionsIsoform selectivityTetra-n-butylammoniumEfficient synthetic procedureSynthetic procedureTrifluoroacetic acidExcellent potencyRat neuronal nitric oxide synthaseNeuronal nitric oxide synthaseInhibitor designNovel inhibitorsNitric oxide synthasePermeable inhibitorStructural insightsEndothelial nitric oxide synthasePermeability assayInducible nitric oxide synthaseCrystalA Tetrahydrobiopterin-Displacing Potent Neuronal Nitric Oxide Synthase Inhibitor with an Unprecedented Binding Mode
Weerawarna P, Li H, Rathnayake A, Hardy C, Poulos T, Silverman R. A Tetrahydrobiopterin-Displacing Potent Neuronal Nitric Oxide Synthase Inhibitor with an Unprecedented Binding Mode. ACS Medicinal Chemistry Letters 2025, 16: 651-659. PMID: 40236557, PMCID: PMC11995208, DOI: 10.1021/acsmedchemlett.5c00062.Peer-Reviewed Original ResearchBinding modeX-ray crystallographic studiesX-rayX-ray crystallography dataHuman nNOS inhibitorsExcellent selectivityRegulate various physiological processesCrystallographic studiesCrystallography dataNitric oxide synthaseHybrid inhibitorsEvaluation of bindingObserved potencyHuman eNOSNitric oxide synthase isoformsCompoundsPhysiological processesNeuronal NOSNeurodegenerative diseasesInhibitory activityDesign rationaleIsoformsNNOS inhibitorNeuronal nitric oxide synthase inhibitorNitric oxide synthase inhibitorInhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases
Johnson E, Nowar R, Viola K, Huang W, Zhou S, Bicca M, Zhu W, Kranz D, Klein W, Silverman R. Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2402117122. PMID: 40030015, PMCID: PMC11912461, DOI: 10.1073/pnas.2402117122.Peer-Reviewed Original ResearchConceptsProtein aggregationNeurodegenerative diseasesMechanisms of protein aggregationAmyloid-beta oligomersAlzheimer's disease neurodegenerationEndolysosomal traffickingBeta oligomersOligomer accumulationTreatment of neurodegenerative diseasesTDP-43Disease neurodegenerationPeptide aggregationLysosome-dependentCathepsin LProteinHippocampal neuronsPathological accumulationQuantitative assayTraffickingCellular mechanismsCathepsin BBlock neurodegenerationImmunofluorescence imagingPathogenic mechanismsNeurodegenerationCrosstalk Between nNOS/NO and COX-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression
Patel A, Tong S, Roosan M, Syed B, Awasthi A, Silverman R, Yang S. Crosstalk Between nNOS/NO and COX-2 Enhances Interferon-Gamma-Stimulated Melanoma Progression. Cancers 2025, 17: 477. PMID: 39941844, PMCID: PMC11816268, DOI: 10.3390/cancers17030477.Peer-Reviewed Original ResearchNeuronal nitric oxide synthaseIFN-gPro-tumorigenic activityCOX-2Human melanoma xenograft mouse modelMelanoma progressionMelanoma cellsFlow cytometryInduction of neuronal nitric oxide synthaseNeuronal nitric oxide synthase blockadeIn vivo antitumor efficacyMelanoma xenograft mouse modelMelanoma tumor microenvironmentLevels of PGE2PD-L1 expressionAnticancer immune responseMelanoma tumor growth in vivoCOX-2 expression levelsAnalysis of patientsInduction of COX-2Increased intracellular NO levelsSTAT3 inhibitor NapabucasinNitric oxideInhibited COX-2 expressionXenograft mouse modelProtection against Amyloid‑β Aggregation and Ferroptosis/Oxytosis Toxicity by Arylpyrazolones: Alzheimer’s Disease Therapeutics
Soares P, Rahaman M, Maher P, Silverman R. Protection against Amyloid‑β Aggregation and Ferroptosis/Oxytosis Toxicity by Arylpyrazolones: Alzheimer’s Disease Therapeutics. ACS Medicinal Chemistry Letters 2025, 16: 294-300. PMID: 39967645, PMCID: PMC11831554, DOI: 10.1021/acsmedchemlett.4c00530.Peer-Reviewed Original ResearchSynthesis of Oxabicyclo[3.2.1]octan-3-ol Scaffold via Burgess Reagent Mediated Cyclodehydration of δ‑Diols under Acidic Conditions
Elmansy M, dos Remedios J, Silverman R. Synthesis of Oxabicyclo[3.2.1]octan-3-ol Scaffold via Burgess Reagent Mediated Cyclodehydration of δ‑Diols under Acidic Conditions. Organic Letters 2025, 27: 640-644. PMID: 39761354, PMCID: PMC11901898, DOI: 10.1021/acs.orglett.4c04473.Peer-Reviewed Original Research
2024
Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction
Wirt J, Ferreira L, Jesus C, Woodward T, Oliva I, Xu Z, Crystal J, Pepin R, Silverman R, Hohmann A. Efficacy of GABA aminotransferase inactivator OV329 in models of neuropathic and inflammatory pain without tolerance or addiction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 122: e2318833121. PMID: 39793055, PMCID: PMC11725897, DOI: 10.1073/pnas.2318833121.Peer-Reviewed Original ResearchConceptsComplete Freund's adjuvantInflammatory painMechanical hypersensitivityAntinociceptive efficacyGlutamate levelsInjection of complete Freund's adjuvantConditioned place preference assayPaclitaxel-induced mechanical hypersensitivitySpinal site of actionSide effectsEnhancement of GABAergic transmissionChemotherapeutic agent paclitaxelPaclitaxel-induced increaseCompared to morphineLumbar spinal cordIncreased endogenous GABA levelsReduced glutamate levelsNeuropathic nociceptionSite of actionGABAergic transmissionAnalgesic strategiesPathological painGABAergic inhibitionSpinal sitesAbuse liabilityCorrection to “Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase”
Devitt A, Vargas A, Zhu W, Des Soye B, Butun F, Alt T, Kaley N, Ferreira G, Moran G, Kelleher N, Liu D, Silverman R. Correction to “Design, Synthesis, and Mechanistic Studies of (R)‑3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase”. ACS Chemical Biology 2024, 19: 1850-1850. PMID: 39023367, DOI: 10.1021/acschembio.4c00478.Peer-Reviewed Original Research