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 Young, MD
Associate Clinical ProfessorAbout
Research
Publications
2025
Protein codes and mobility together shape cellular function and disease
Kilgore H, Moreno S, Young R. Protein codes and mobility together shape cellular function and disease. Trends In Biochemical Sciences 2025, 51: 8-26. PMID: 41318327, PMCID: PMC12703758, DOI: 10.1016/j.tibs.2025.10.009.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMembrane-bound organellesMembrane-less condensatesMovement of proteinsProtein codingProtein foldingBiochemical functionsCellular functionsProtein propertiesBiochemical activityCellular healthProtein mobilityBiochemical ratesProteinDisease pathologyCondenser compartmentCompartmentNormal functionOrganellesCompartmentalizationFoldingDynamic movementCRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNAs
Morelli E, Aktas-Samur A, Maisano D, Gao C, Favasuli V, Papaioannou D, De Nola G, Henninger J, Liu N, Turi M, Folino P, Vreux L, Cumerlato M, Chen L, Aifantis I, Fulciniti M, Anderson K, Lytton-Jean A, Gulla A, Young R, Samur M, Munshi N. CRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNAs. Blood 2025, 146: 847-860. PMID: 40403231, PMCID: PMC12783513, DOI: 10.1182/blood.2025028746.Peer-Reviewed Original ResearchCRISPR-Cas13dMultiple myelomaTE-lncRNAsIsoform-specific functionsDiverse cancer cell linesMM patientsCancer cell linesCellular proteostasisSubcellular localizationTumor cellsClinical dataCancer transcriptomeCytosolic isoformEndoplasmic reticulumFunctional transcriptomeHeat shock proteinsCancer dependenciesMM-specificClinical relevanceAnimal modelsLong noncoding RNAsLncRNA transcriptomeTherapeutic potentialCharacterize hundredsTranscriptomeExploring the complexity of MECP2 function in Rett syndrome
Liu Y, Whitfield T, Bell G, Guo R, Flamier A, Young R, Jaenisch R. Exploring the complexity of MECP2 function in Rett syndrome. Nature Reviews Neuroscience 2025, 26: 379-398. PMID: 40360671, DOI: 10.1038/s41583-025-00926-1.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMethylated DNA binding protein MeCP2Neuronal gene regulationReview recent insightsChromatin structureTranscriptional regulationGene regulationInteraction hubProtein MeCP2Cofactor interactionsTranscription factorsEpigenetic regulationRett syndromeProteomic studiesDiverse processesMolecular mechanismsMeCP2 functionTherapeutic designMeCP2Neuronal functionRegulationModel systemNeurodevelopmental disordersRepressorChromatinMechanistic studiesProtein codes promote selective subcellular compartmentalization
Kilgore H, Chinn I, Mikhael P, Mitnikov I, Van Dongen C, Zylberberg G, Afeyan L, Banani S, Wilson-Hawken S, Lee T, Barzilay R, Young R. Protein codes promote selective subcellular compartmentalization. Science 2025, 387: 1095-1101. PMID: 39913643, PMCID: PMC12034300, DOI: 10.1126/science.adq2634.Peer-Reviewed Original ResearchConceptsProtein sequencesSubcellular compartmentsDiverse subcellular compartmentsProtein language modelsAmino acid sequenceProtein codingAcid sequenceSubcellular localizationDiverse proteinsHuman proteinsSubcellular compartmentalizationFolding codePathological mutationsCompartment localizationProteinSequenceCompartmentMutationsAminoNucleolusCompartmentalizationCells
2024
Proteolethargy is a pathogenic mechanism in chronic disease
Dall'Agnese A, Zheng M, Moreno S, Platt J, Hoang A, Kannan D, Dall'Agnese G, Overholt K, Sagi I, Hannett N, Erb H, Corradin O, Chakraborty A, Lee T, Young R. Proteolethargy is a pathogenic mechanism in chronic disease. Cell 2024, 188: 207-221.e30. PMID: 39610243, PMCID: PMC11724756, DOI: 10.1016/j.cell.2024.10.051.Peer-Reviewed Original ResearchPathogenic signalsExcessive reactive oxygen speciesMobility phenotypeCellular functionsAffected proteinsPathogenic mechanismsReactive oxygen speciesCysteine residuesSpectra of proteinsProtein mobilityPathogenic stimuliPathogenic featuresOxygen speciesMolecular levelCellular mechanismsDiverse chronic diseasesProteinChronic diseasesAn RNA-centric view of transcription and genome organization
Henninger J, Young R. An RNA-centric view of transcription and genome organization. Molecular Cell 2024, 84: 3627-3643. PMID: 39366351, PMCID: PMC11495847, DOI: 10.1016/j.molcel.2024.08.021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGene regulationGenome architectureTranscriptional regulationModel of transcriptional regulationAssembly of protein complexesAssembly of transcription complexesLocal genome architectureSilencing of genesGenomic compartmentsGenome organizationGenomic structureRNA polymeraseChromatin regulationTranscription complexActive genesProtein complexesRNA moleculesTranscription factorsGenomeProtein kinaseSpecific genesGenesFeedback regulationRNASpatial compartmentsRNA and condensates: Disease implications and therapeutic opportunities
Han T, Portz B, Young R, Boija A, Klein I. RNA and condensates: Disease implications and therapeutic opportunities. Cell Chemical Biology 2024, 31: 1593-1609. PMID: 39303698, DOI: 10.1016/j.chembiol.2024.08.009.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRegulate key cellular processesDiverse RNA speciesRNA speciesTarget RNACompartmentalizing proteinsCellular processesRNA moleculesMembraneless organellesRNA roleBiomolecular condensatesRNA-based therapiesComplex diseasesRNA abnormalitiesRNADisease pathogenesisCondensate formationProperties of condensatesTherapeutic strategiesSmall moleculesOrganellesMislocalizationOverexpressionProteinSpeciesNeurological disordersMECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons
Liu Y, Flamier A, Bell G, Diao A, Whitfield T, Wang H, Wu Y, Schulte F, Friesen M, Guo R, Mitalipova M, Liu X, Vos S, Young R, Jaenisch R. MECP2 directly interacts with RNA polymerase II to modulate transcription in human neurons. Neuron 2024, 112: 1943-1958.e10. PMID: 38697112, DOI: 10.1016/j.neuron.2024.04.007.Peer-Reviewed Original ResearchPromoter-proximal regionRNA polymerase IIPolymerase IIHuman neuronsMethylated DNA binding protein MeCP2RNA Pol IIWild-typeLoss of gene activityAutism risk genesPol IIPositive cofactorCpG islandsTranscriptional regulationModulate transcriptionProtein MeCP2Patient mutationsNeurodevelopmental disorder Rett syndromeGene activationRisk genesProteomic analysisNeuronal genesRett syndromeGene expressionGenesRNA
1990
Conditional Mutations Occur Predominantly in Highly Conserved Residues of RNA Polymerase II Subunits
Scafe C, Martin C, Nonet M, Podos S, Okamura S, Young R. Conditional Mutations Occur Predominantly in Highly Conserved Residues of RNA Polymerase II Subunits. Molecular And Cellular Biology 1990, 10: 1270-1275. DOI: 10.1128/mcb.10.3.1270-1275.1990.Peer-Reviewed Original ResearchRNA polymerase II largest subunitRNA polymerase mutantsAmino acid residuesRPB1 geneLarge subunitInvariant residuesEucaryotic organismsPolymerase mutantsConditional mutationsYeast cellsSequence analysisAcid residuesRPB2RPB1MutationsCold sensitivityResiduesYeastMutantsCellsHomologyPlasmidGenesRNASubunit
1989
RNA Polymerase II Subunit RPB4 Is Essential for High- and Low-Temperature Yeast Cell Growth
Woychik N, Young R. RNA Polymerase II Subunit RPB4 Is Essential for High- and Low-Temperature Yeast Cell Growth. Molecular And Cellular Biology 1989, 9: 2854-2859. DOI: 10.1128/mcb.9.7.2854-2859.1989.Peer-Reviewed Original ResearchRPB4 subunitRNA polymerase II subunitEscherichia coli RNA polymeraseSequence analysis of tryptic peptidesAmino acid sequence analysis of tryptic peptidesRNA polymerase II activityAmino acid sequence analysisDeletion of RPB4Polymerase II subunitAnalysis of tryptic peptidesRNA polymerase IIAmino acidsPolymerase II activityRPB4 geneSigma subunitCrude extracts in vitroPolymerase IIRNA polymeraseSaccharomyces cerevisiaeEnzyme assemblyDNA sequencesRpb4Purified subunitsExtracts in vitroMRNA synthesis