Ashish Kumar, PhD
About
Titles
Postdoctoral Associate in Pharmacology
Biography
I earned my Ph.D. under the guidance of Dr. Dileep Vasudevan at the Institute of Life Sciences, Bhubaneswar, India. Currently, I am working as a postdoctoral associate in the Department of Pharmacology at Yale University under the mentorship of Prof. Joseph Schlessinger.
During my doctoral studies, I spearheaded diverse research projects that centered on the structural and biophysical characterization of plant chromatin and plant-specific histone chaperones. My research endeavors aimed to unravel the intricate mechanisms governing plant chromatin dynamics. Utilizing X-ray Crystallography as my primary investigative tool, in combination with complementary biophysical techniques like SAXS and AUC, I made substantial contributions to our comprehension of plant chromatin regulation, particularly concerning stress-specific histone chaperones of the NRP family and HDT family. Notably, my Ph.D. work led to the discovery that plant HDTs function as histone chaperones within the nucleoplasmin family rather than actively participating in deacetylation.
In my initial postdoctoral role, my research focused on elucidating the mechanisms governing DNA replication initiation in metazoans. Employing an integrative structural biology approach that involved the biochemical reconstitution of nucleosome complexes, mass spectrometry, and cryo-EM, I have co-authored two publications during my tenure at Yale. These studies shed light on how inhibitory signals, such as phosphorylation by cyclin-dependent kinases, can impede DNA replication initiation factor loading. Additionally, we unveiled the pivotal role played by the initiation factor ORC-associated protein, ORCA, in facilitating DNA replication initiation within the context of condensed chromatin. My primary contributions encompassed the preparation of modified histones, nucleosomes, and nucleosome arrays, as well as the execution of various biochemical experiments.
My ongoing research in Prof. Schlessinger's lab centers on solving the cryo-EM structures of receptor tyrosine kinases (RTKs) in complex with their ligands and other signaling molecules.
Appointments
Education & Training
- PhD
- Institute of Life Sciences (2020)
- MSc
- Babasaheb Bhimrao Ambedkar University, Biotechnology (2013)
- BSc
- Patna University, Biotechnology (2011)
Research
Research at a Glance
Yale Co-Authors
Publications Timeline
Franziska Bleichert, PhD
Sunanda Mallik
Publications
2023
A dual role for the chromatin reader ORCA/LRWD1 in targeting the origin recognition complex to chromatin
Sahu S, Ekundayo B, Kumar A, Bleichert F. A dual role for the chromatin reader ORCA/LRWD1 in targeting the origin recognition complex to chromatin. The EMBO Journal 2023, 42: e114654. PMID: 37551430, PMCID: PMC10505921, DOI: 10.15252/embj.2023114654.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsOrigin recognition complexH4K20 trimethylationHeterochromatin replicationRecognition complexCryo-electron microscopy structureLocal chromatin environmentSpecific histone marksSpecific chromatin contextsMcm2-7 loadingTernary complex assemblyChromatin environmentChromatin marksChromatin contextHistone marksHistone modificationsReplication initiationEukaryotic cellsMicroscopy structureChromatin condensatesORC recruitmentDNA replicationMammalian cellsNucleosomal DNAAromatic cageComplex assembly
2022
Plant-specific HDT family histone deacetylases are nucleoplasmins
Bobde R, Kumar A, Vasudevan D. Plant-specific HDT family histone deacetylases are nucleoplasmins. The Plant Cell 2022, 34: 4760-4777. PMID: 36069647, PMCID: PMC9709999, DOI: 10.1093/plcell/koac275.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsN-terminal domainHistone chaperonesH2A/H2B dimersHistones H3/H4H3/H4Nucleosome dynamicsH2B dimersSequence similarityHistone acetyltransferaseEnigmatic familyHistone acetylationFunctional characterizationNucleoplasminGene expressionHistone deacetylasesC-terminalHistone deacetylaseUrea conditionsHistone oligomersSolution structureChaperonesDifferent familiesArabidopsisA mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6
Schmidt JM, Yang R, Kumar A, Hunker O, Seebacher J, Bleichert F. A mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6. Nature Communications 2022, 13: 1059. PMID: 35217664, PMCID: PMC8881611, DOI: 10.1038/s41467-022-28695-w.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsOrigin recognition complexS. cerevisiaeCyclin-dependent kinase phosphorylationMcm2-7 loadingN-terminal domainCryo-electron microscopyCDK phosphorylationRecognition complexDNA replicationReplication originsÅ resolutionKinase phosphorylationMechanism of originCdc6Coordinated actionCerevisiaePhosphorylationDNAInhibitory signalsStructural detailsSite regulationRecruitmentOrc6AssemblyCdt1
2021
In Vitro Characterization of Histone Chaperones using Analytical, Pull-Down and Chaperoning Assays.
Bobde R, Saharan K, Baral S, Gandhi S, Samal A, Sundaram R, Kumar A, Singh A, Datta A, Vasudevan D. In Vitro Characterization of Histone Chaperones using Analytical, Pull-Down and Chaperoning Assays. Journal Of Visualized Experiments 2021 PMID: 35037657, DOI: 10.3791/63218.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHistone chaperonesH3/H4 tetramersNucleosome assembly processH3/H4H2A/H2BCore histones H2APull-down assaysAnalytical size exclusion chromatographyEukaryotic chromatinH4 tetramersHistone H2AH2A/Core histonesHistone octamerSingle copyChaperonesHistonesCellular cytoplasmDiverse classChromatinProteinDNAH2BH4Non-specific interactions<em>In Vitro</em> Characterization of Histone Chaperones using Analytical, Pull-Down and Chaperoning Assays
Bobde R, Saharan K, Baral S, Gandhi S, Samal A, Sundaram R, Kumar A, Singh A, Datta A, Vasudevan D. In Vitro Characterization of Histone Chaperones using Analytical, Pull-Down and Chaperoning Assays. Journal Of Visualized Experiments 2021 DOI: 10.3791/63218-v.Peer-Reviewed Original ResearchBiochemical characterization of an E. coli cell division factor FtsE shows ATPase cycles similar to the NBDs of ABC-transporters
Mallick S, Kumar A, Dodia H, Alexander C, Vasudevan D, Beuria T. Biochemical characterization of an E. coli cell division factor FtsE shows ATPase cycles similar to the NBDs of ABC-transporters. Bioscience Reports 2021, 41: bsr20203034. PMID: 33320186, PMCID: PMC7791547, DOI: 10.1042/bsr20203034.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsFtsEX complexPG hydrolysisABC transportersCytoplasmic loopBiochemical characterizationATPase cycleCouple ATP hydrolysisATP-binding siteATPase activityE. coliBacterial cell wallTransduce signalsInner membraneSequence similarityBacterial divisionSignal transductionPeptidoglycan layerMid cellATP hydrolysisCell wallSoluble expressionBiochemical propertiesFtsE.Direct interactionTransport molecules
2019
Structure-function relationship of H2A-H2B specific plant histone chaperones
Kumar A, Vasudevan D. Structure-function relationship of H2A-H2B specific plant histone chaperones. Cell Stress And Chaperones 2019, 25: 1-17. PMID: 31707537, PMCID: PMC6985425, DOI: 10.1007/s12192-019-01050-7.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsHistone chaperonesNucleosome assembly proteinChromatin organizationStructure-function relationshipsPlant chromatin organizationNucleosome assembly/Dynamic chromatin organizationVital nuclear functionsPlant chromatinChaperone familyChromatin transcriptionChaperone structuresChromatin structureNuclear functionsEpigenetic regulationDNA recombinationAssembly proteinDNA replicationH2A-H2BDNA repairChaperonesMore isoformsStress conditionsAssembly/PlantsStructural Characterization of Arabidopsis thaliana NAP1-Related Protein 2 (AtNRP2) and Comparison with Its Homolog AtNRP1
Kumar A, Singh A, Bobde R, Vasudevan D. Structural Characterization of Arabidopsis thaliana NAP1-Related Protein 2 (AtNRP2) and Comparison with Its Homolog AtNRP1. Molecules 2019, 24: 2258. PMID: 31213016, PMCID: PMC6630525, DOI: 10.3390/molecules24122258.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNucleosome assembly proteinHistone chaperonesFamily proteinsNAP familyIsothermal titration calorimetry experimentsTitration calorimetry experimentsAssembly proteinOligomerization statusPlant tissuesSequence identityDimerization helixSimilar foldSimilar proteinsBiophysical studiesSpecific functionsStructural superpositionProtein 2ProteinPlantsChaperonesElectrophoretic mobilityStructural studiesCrystal structureThermal melting experimentsStructural architecture
2014
Plant immunophilins: a review of their structure-function relationship
Vasudevan D, Gopalan G, Kumar A, Garcia V, Luan S, Swaminathan K. Plant immunophilins: a review of their structure-function relationship. Biochimica Et Biophysica Acta 2014, 1850: 2145-2158. PMID: 25529299, DOI: 10.1016/j.bbagen.2014.12.017.Peer-Reviewed Original ResearchCitationsMeSH Keywords and ConceptsConceptsPlant immunophilinsPlant biologyProtein foldingRegulation of photosynthesisLittle sequence homologyCell Signaling CatalystsPeptidyl-prolyl isomeraseProtein folding processLittle structural informationStructure-function relationshipsPhotosynthetic organellesMolecular chaperonesFunctional diversityProlyl isomeraseThylakoid lumenSubcellular localizationSequence homologyCYP familiesImmunophilinsPlant systemsDrug targetsFolding processMajor groupsNew functionsFKBP
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Contacts
Pharmacology
Room No B286, YSM 333 Cedar Street
New Haven, Connecticut 06510
United States
Locations
Schlessinger's lab
Lab
Sterling Hall of Medicine
333 Cedar Street, Wing B, Fl 2, Rm 286
New Haven, CT 06510