Matt Simon, PhD
he/him/his
Associate Professor TenureDownloadHi-Res Photo
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Additional Titles
Associate Professor of Molecular Biophysics and Biochemistry, Associate Professor of Institute of Biomolecular Design & Discovery
Contact Info
Molecular Biophysics and Biochemistry
Yale's Chemical Biology Institute, P.O. BOX 27392
West Haven, CT 06516-7392
United States
Appointments
Additional Titles
Associate Professor of Molecular Biophysics and Biochemistry, Associate Professor of Institute of Biomolecular Design & Discovery
Contact Info
Molecular Biophysics and Biochemistry
Yale's Chemical Biology Institute, P.O. BOX 27392
West Haven, CT 06516-7392
United States
Appointments
Additional Titles
Associate Professor of Molecular Biophysics and Biochemistry, Associate Professor of Institute of Biomolecular Design & Discovery
Contact Info
Molecular Biophysics and Biochemistry
Yale's Chemical Biology Institute, P.O. BOX 27392
West Haven, CT 06516-7392
United States
About
Titles
Associate Professor Tenure
Associate Professor of Molecular Biophysics and Biochemistry, Associate Professor of Institute of Biomolecular Design & Discovery
Biography
Matt grew up in Ann Arbor, MI and received his Ph.D. in Chemistry from UC Berkeley. He commuted between Berkeley and UCSF, working with Kevan Shokat developing chemical methods to make synthetic chromatin substrates to study the biochemistry of epigenetics. He continued this work as a Helen Hay Whitney Foundation post doctoral fellow in Robert Kingston's laboratory at the Massachusetts General Hospital, where his interests expanded to include large non-coding RNAs and their impact on chromatin. In 2012 he joined the faculty at Yale. He is part of the Institute for Bimolecular Design & Discovery on Yale's West Campus, and The Department of Molecular Biophysics & Biochemistry, where his group's research focuses on developing new chemical and biochemical means of investigating regulated gene expression at the level of chromatin and RNA biology.
Appointments
Molecular Biophysics and Biochemistry
Associate Professor TenurePrimary
Other Departments & Organizations
Education & Training
- PhD
- University of California at Berkeley, Chemistry (2006)
- BA
- Tufts University, Biochemistry (1999)
Research
Overview
Medical Subject Headings (MeSH)
Biochemistry; Biophysics; Chromatin; RNA, Untranslated
ORCID
0000-0001-7423-5265- View Lab Website
The Simon Lab
Research at a Glance
Yale Co-Authors
Frequent collaborators of Matt Simon's published research.
Publications Timeline
A big-picture view of Matt Simon's research output by year.
Research Interests
Research topics Matt Simon is interested in exploring.
Karla M Neugebauer, PhD
Haifan Lin, PhD
Nils Neuenkirchen, PhD
Craig B. Wilen, MD, PhD
Giulia Biancon, PhD
Joan Steitz, PhD
35Publications
2,821Citations
Chromatin
RNA, Untranslated
Publications
Featured Publications
STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts
Zimmer JT, Rosa-Mercado NA, Canzio D, Steitz JA, Simon MD. STL-seq reveals pause-release and termination kinetics for promoter-proximal paused RNA polymerase II transcripts. Molecular Cell 2021, 81: 4398-4412.e7. PMID: 34520723, PMCID: PMC9020433, DOI: 10.1016/j.molcel.2021.08.019.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPause releaseRNA polymerase II transcriptsRNA polymerase II moleculesCis-acting DNA elementsTATA box-containing promotersPolymerase II transcriptsPromoter-proximal pausingCritical regulatory functionsTranscriptional regulationRNA turnoverTranscriptional controlDNA elementsTranscriptional shutdownPause sitesHyperosmotic stressRegulatory mechanismsRegulatory functionsPrinciples of regulationHormonal stimuliPausingPremature terminationTranscriptsRegulationAcetyl-methyllysine marks chromatin at active transcription start sites
Lu-Culligan W, Connor L, Xie Y, Ekundayo B, Rose B, Machyna M, Pintado-Urbanc A, Zimmer J, Vock I, Bhanu N, King M, Garcia B, Bleichert F, Simon M. Acetyl-methyllysine marks chromatin at active transcription start sites. Nature 2023, 622: 173-179. PMID: 37731000, PMCID: PMC10845139, DOI: 10.1038/s41586-023-06565-9.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsPost-translational modificationsLysine residuesActive transcription start sitesTranscription start siteRange of speciesChromatin biologyChromatin proteinsLysine methylationActive chromatinProteins BRD2Transcriptional initiationLysine acetylationHistone H4Start siteMammalian tissuesHuman diseasesSame residuesMethylationAcetylationChromatinResiduesProteinBiological signalsHistonesBRD2Enhanced nucleotide chemistry and toehold nanotechnology reveals lncRNA spreading on chromatin
Machyna M, Kiefer L, Simon MD. Enhanced nucleotide chemistry and toehold nanotechnology reveals lncRNA spreading on chromatin. Nature Structural & Molecular Biology 2020, 27: 297-304. PMID: 32157249, DOI: 10.1038/s41594-020-0390-z.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHybridization capture approachGenome-wide changesLong non-coding RNAsUnfolded protein responseNon-coding RNAsStrand exchange reactionLncRNA localizationIndividual RNAsRNA captureUncharacterized changesX chromosomeProtein responseHeat shockChromatinLncRNAsRNACapture approachBinding sitesNucleic acidsNucleotide chemistryRoX2AutosomesChromosomesRelocalizationSpeciesTimeLapse-seq: adding a temporal dimension to RNA sequencing through nucleoside recoding
Schofield JA, Duffy EE, Kiefer L, Sullivan MC, Simon MD. TimeLapse-seq: adding a temporal dimension to RNA sequencing through nucleoside recoding. Nature Methods 2018, 15: 221-225. PMID: 29355846, PMCID: PMC5831505, DOI: 10.1038/nmeth.4582.Peer-Reviewed Original ResearchCitationsAltmetricHigh-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation
Simon MD, Pinter SF, Fang R, Sarma K, Rutenberg-Schoenberg M, Bowman SK, Kesner BA, Maier VK, Kingston RE, Lee JT. High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature 2013, 504: 465-469. PMID: 24162848, PMCID: PMC3904790, DOI: 10.1038/nature12719.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and Concepts
2024
Disulfide Tethering to Map Small Molecule Binding Sites Transcriptome-wide
Moon M, Vock I, Streit A, Connor L, Senkina J, Ellman J, Simon M. Disulfide Tethering to Map Small Molecule Binding Sites Transcriptome-wide. ACS Chemical Biology 2024, 19: 2081-2086. PMID: 39192734, DOI: 10.1021/acschembio.4c00538.Peer-Reviewed Original ResearchAltmetricConceptsCytochrome c oxidase 1Binding sitesRNA-small molecule interactionsPotential binding sitesTranscriptome-wide screeningSmall molecule disulfideSpinal muscular atrophyCellular RNARNA sitesTarget RNAMetabolic labelingSmall molecule bindingRNADisulfide analoguesLead moleculesMolecule bindingTranscriptomeFDA-approved drugsStructural probesMolecule interactionsCovalent attachmentDisulfide tetherThermodynamic propertiesTreat spinal muscular atrophyDisulfidePhosphorylation of the nuclear poly(A) binding protein (PABPN1) during mitosis protects mRNA from hyperadenylation and maintains transcriptome dynamics
Gordon J, Phizicky D, Schärfen L, Brown C, Escayola D, Kanyo J, Lam T, Simon M, Neugebauer K. Phosphorylation of the nuclear poly(A) binding protein (PABPN1) during mitosis protects mRNA from hyperadenylation and maintains transcriptome dynamics. Nucleic Acids Research 2024, 52: 9886-9903. PMID: 38943343, PMCID: PMC11381358, DOI: 10.1093/nar/gkae562.Peer-Reviewed Original ResearchAltmetricConceptsPoly(A)-binding proteinTranscriptome dynamicsNuclear poly(A) binding proteinPoly(A) binding proteinMode of gene regulationFunctional consequences of phosphorylationLong-read sequencingIncreased mRNA turnoverNucleo-cytoplasmic exportConsequences of phosphorylationRegulation of poly(ACohort of mRNAsGene expression programsMRNA biogenesisCytoplasmic mixingMRNA turnoverGene regulationShorter poly(ARNA stabilityMitotic kinasesPoly(ACell cycleMRNA synthesisIncreased transcriptionBinding proteinTranscription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape
Boddu P, Gupta A, Roy R, De La Peña Avalos B, Olazabal-Herrero A, Neuenkirchen N, Zimmer J, Chandhok N, King D, Nannya Y, Ogawa S, Lin H, Simon M, Dray E, Kupfer G, Verma A, Neugebauer K, Pillai M. Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape. Molecular Cell 2024, 84: 1475-1495.e18. PMID: 38521065, PMCID: PMC11061666, DOI: 10.1016/j.molcel.2024.02.032.Peer-Reviewed Original ResearchCitationsAltmetricConceptsRate of RNA polymerase IIChromatin landscapeElongation defectsElongation rate of RNA polymerase IIImpaired protein-protein interactionsSplicing of pre-messenger RNATranscription elongation defectsRNA polymerase IIProtein-protein interactionsPre-messenger RNACancer-associated mutationsIsogenic cell linesSin3/HDAC complexGene bodiesPolymerase IIChromatin accessibilityH3K4me3 markChromatin changesMutant SF3B1ChromatinMutant mouse modelsEpigenetic disordersEpigenetic factorsHuman diseasesMutant state
2023
Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E
Boddu P, Gupta A, Roy R, De La Pena Avalos B, Herrero A, Zimmer J, Simon M, Chandhok N, King D, Neuenkirchen N, Dray E, Lin H, Kupfer G, Verma A, Neugebauer K, Pillai M. Impaired Early Spliceosome Complex Assembly Underlies Gene Body Elongation Transcription Defect in SF3B1K700E. Blood 2023, 142: 714. DOI: 10.1182/blood-2023-187303.Peer-Reviewed Original ResearchCitationsConceptsSplicing factorsChIP-seqK562 cell lineKey regulatory genesCell linesSingle mutant alleleNon-denaturing gelsAlternative splicingTranscriptional kineticsRegulatory genesSpliceosome assemblySplicing efficiencyMRNA splicingCRISPR/Progenitor populationsNeomorphic functionsMolecular mechanismsMutant allelesIsoform changesGene editingNovel mechanismMutationsSF mutationsRecurrent mutationsAssembly kineticsALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m6A modification-mediated RNA stability control
Gao Y, Zimmer J, Vasic R, Liu C, Gbyli R, Zheng S, Patel A, Liu W, Qi Z, Li Y, Nelakanti R, Song Y, Biancon G, Xiao A, Slavoff S, Kibbey R, Flavell R, Simon M, Tebaldi T, Li H, Halene S. ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m6A modification-mediated RNA stability control. Cell Reports 2023, 42: 113163. PMID: 37742191, PMCID: PMC10636609, DOI: 10.1016/j.celrep.2023.113163.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsAlkB homolog 5Post-transcriptional regulatory mechanismsHematopoietic stemNumerous cellular processesProgenitor cell fitnessEnergy metabolismMitochondrial ATP productionMethyladenosine (m<sup>6</sup>A) RNA modificationTricarboxylic acid cycleCell energy metabolismHuman hematopoietic cellsMitochondrial energy productionCell fitnessCellular processesRNA modificationsRNA methylationRegulatory mechanismsEnzyme transcriptsATP productionHomolog 5Acid cycleΑ-ketoglutarateHematopoietic cellsMessenger RNAΑ-KG
Academic Achievements & Community Involvement
honor Post Doctoral Fellowship
National AwardHelen Hay Whitney FoundationDetails07/01/2007United States
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Molecular Biophysics and Biochemistry
Yale's Chemical Biology Institute, P.O. BOX 27392
West Haven, CT 06516-7392
United States
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