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Understanding programs of invasion and metastasis in head and neck cancer

Understanding programs of invasion and metastasis in head and neck cancer
了解头颈癌的侵袭和转移程序
批准号:
10679102
负责人:
Sidharth Venkata Puram
金额:
$16.39万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-09-01 至 2023-10-01
关键词:
3-DimensionalAdvisory CommitteesApplied SkillsAppointmentAtlasesAutomobile DrivingAwardBiochemicalBiochemistryBiologicalBiological AssayBrainCRISPR/Cas technologyCancer ModelCell LineCellsCellular AssayCellular biologyCessation of lifeChIP-seqChemicalsChromatinClinicalCoculture TechniquesCollaborationsCommunicationComplementCultured CellsData SetDevelopmentDiseaseDistant MetastasisDoctor of PhilosophyDrug DesignEnhancersEnvironmentEpigenetic ProcessEpitheliumExtracapsularFGF7 geneFibroblastsFlow CytometryFosteringGene ExpressionGenesGenetic TranscriptionGenomeGenomicsGliomaGoalsHead and Neck CancerHead and Neck Squamous Cell CarcinomaHead and Neck SurgeryHeterogeneityHistone AcetylationHistone H3HumanITGA5 geneImmuneIn VitroInternationalInvadedLAMC2 geneLaboratoriesLeadershipLigandsLinkLysineMMP2 geneMalignant - descriptorMalignant NeoplasmsMapsMass Spectrum AnalysisMediatingMentorsMesenchymalMetastatic Neoplasm to Lymph NodesMicrofluidic MicrochipsModelingMorbidity - disease rateNational Cancer Advisory BoardNeoplasm MetastasisOncogenesOncologyOperative Surgical ProceduresPathway interactionsPatientsPhenotypePopulationPositioning AttributeProcessProfessional counselorPrognosisProliferatingRadiation therapyRecording of previous eventsRegulationReporterResearchResearch InstituteResearch ProposalsRoleSTAT3 geneSignal PathwaySignal TransductionSolid NeoplasmSortingStromal Cell-Derived Factor 1Surgical OncologyTGFBI geneTechniquesTestingThe Cancer Genome AtlasTrainingTranscriptional RegulationTransforming Growth Factor betaTranslatingTransposaseTreatment outcomeTumor BiologyTumor Cell InvasionTumor SubtypeTumor Suppressor ProteinsUniversitiesWashingtonadvanced diseasecancer cellcareerchemotherapydifferential expressionepigenetic regulationexperimental studyin vivoinhibitorinnovationinnovative technologiesinterestlymph nodeslymphatic Invasionmembermolecular oncologymortalityneoplastic cellnovel therapeuticsoverexpressionpatient derived xenograft modelpharmacologicpost-doctoral trainingprogramsreceptorsingle-cell RNA sequencingskillssmall hairpin RNAsmall moleculetargeted treatmenttherapeutically effectivetranscription factortranscriptome sequencingtreatment responsetumortumor behaviortumor heterogeneity

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中文摘要
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英文摘要
PROJECT SUMMARY Intra-tumoral heterogeneity in human cancers is associated with poor treatment response and prognosis. Head and neck squamous cell carcinoma (HNSCC) is a strikingly heterogeneous tumor, with over 550,000 new cases per year. Unfortunately, this heterogeneity represents a major challenge in targeted therapy and treatment responses, with detailed maps of intra-tumoral heterogeneity just starting to be defined. During my Ph.D. training with Dr. Azad Bonni, I studied normal processes of brain development using sophisticated biochemistry techniques 1,2,3,4, which inspired me to understand the signaling pathways that drive specific biological programs. I applied these skills to studies of glioma, ultimately, defining a dual role for the transcription factor STAT3 as a tumor suppressor and an oncogene 5,6,7. For my post-doctoral training, I joined the laboratory of Dr. Bradley Bernstein, an expert in transcription, epigenetics, and innovative technology, to combine my interests in tumor heterogeneity with my clinical interests in head and neck surgical oncology. Using single cell RNA-seq, we defined the first atlas of HNSCC, identifying a partial epithelial-to-mesenchymal (p-EMT) program associated with lymph node metastasis, lymphovascular invasion, and extracapsular extension8. We also refined tumor subtyping from bulk RNA-seq approaches such as the Cancer Genome Atlas by leveraging our single cell profiles. The objectives of this proposal are to (1) determine expression heterogeneity within 2D and 3D head and neck cancer models and identify suitable models of p-EMT, (2) investigate the regulatory influence of cancer-associated fibroblasts and their ligands on malignant cancer cell states, including the underlying transcriptional and epigenetic mechanisms, and (3) define the signaling pathways downstream of p-EMT and discern their functional importance in tumor behaviors. Dr. Tim Ley and Dr. Greg Longmore are exceptional mentors with an extensive history of trainees in major academic positions. Dr. Ley is an internationally renowned leader in oncology, genomics, and tumor biology, with appointments including Associate Director of the Siteman Cancer and the McDonnell Genome Institute at Washington University St. Louis (WUSTL), National Cancer Advisory Board Member, and former Chair of Board of Scientific Counselors for National Institute Genome Research Institute. Similarly, Dr. Greg Longmore is a world expert in molecular oncology, EMT, and cell biology, with appointments as Co-Director of Molecular Oncology and Director of the Integrating Communications within the Cancer Environment Institute, WUSTL. An exceptional Research Advisory Committee (RAC) will provide additional guidance, including Dr. Ting Wang, Dr. Jose Zevallos, and Dr. Rob Mitra. The K08 award will provide me with the ideal opportunity to succeed in my career goals. The detailed training plan includes a RAC and development of technical/leadership skills that will be invaluable for a transition to independence. Research will be carried out at WUSTL, a prestigious research institute that fosters collaboration, emphasizes intellectual exchange, and boasts unparalleled facilities.
期刊论文(9)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1136/jitc-2020-001048
发表时间: 2020-09
期刊: Journal for immunotherapy of cancer
影响因子: 10.9
作者: [Parikh A, Shin J, Faquin W, Lin DT, Tirosh I, Sunwoo JB, Puram SV]
通讯作者: Puram SV
DOI: 10.1038/s41588-020-00726-6
发表时间: 2020-11
期刊: Nature genetics
影响因子: 30.8
作者: [Kinker GS, Greenwald AC, Tal R, Orlova Z, Cuoco MS, McFarland JM, Warren A, Rodman C, Roth JA, Bender SA, Kumar B, Rocco JW, Fernandes PACM, Mader CC, Keren-Shaul H, Plotnikov A, Barr H, Tsherniak A, Rozenblatt-Rosen O, Krizhanovsky V, Puram SV, Regev A, Tirosh I]
通讯作者: Tirosh I
DOI: 10.1016/j.oraloncology.2020.104893
发表时间: 2020-11
期刊: Oral oncology
影响因子: 4.8
作者: [Stepan KO, Li MM, Kang SY, Puram SV]
通讯作者: Puram SV
ASO Author Reflections: Margin Analysis in Head and Neck Cancer-State of the Art and Future Directions.
ASO 作者感言:头颈癌的利润分析——最新技术和未来方向。
DOI: 10.1245/s10434-019-07773-2
发表时间: 2019
期刊: Annals of surgical oncology
影响因子: 3.7
作者: [Silverman,DustinA, Li,MichaelM, Puram,SidharthV, Kang,StephenY]
通讯作者: Kang,StephenY
Dissecting hybrid epithelial-mesenchymal states in head and neck cancer
  • 批准号:
    10566685
  • 项目类别:
  • 资助金额:
    $39.17万
  • 财政年份:
    2023
  • 负责人:
    Sidharth Venkata Puram
  • 依托单位:
RNA modification and the regulation of partial EMT in head and neck cancer
  • 批准号:
    10428650
  • 项目类别:
  • 资助金额:
    $23.63万
  • 财政年份:
    2021
  • 负责人:
    Sidharth Venkata Puram
  • 依托单位:
RNA modification and the regulation of partial EMT in head and neck cancer
  • 批准号:
    10285358
  • 项目类别:
  • 资助金额:
    $19.69万
  • 财政年份:
    2021
  • 负责人:
    Sidharth Venkata Puram
  • 依托单位:
Understanding programs of invasion and metastasis in head and neck cancer
  • 批准号:
    10247778
  • 项目类别:
  • 资助金额:
    $21.88万
  • 财政年份:
    2019
  • 负责人:
    Sidharth Venkata Puram
  • 依托单位:
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