Super-Resolution Imaging of Higher-Order Heterochromatin Structure for Early Detection of Lung Carcinogenesis
高阶异染色质结构的超分辨率成像用于早期检测肺癌
基本信息
- 批准号:10592368
- 负责人:
- 金额:$ 18.21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-15 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AgeBiological MarkersCancer EtiologyCancer PatientCarcinogensCellsCessation of lifeCharacteristicsChromatinChromatin StructureChronic Obstructive Pulmonary DiseaseCigarette SmokerClinicalDataData CollectionDetectionDevelopmentDiagnosisEarly DiagnosisEpigenetic ProcessEpithelial CellsEventExhibitsEyeFormalinGoalsHeterochromatinHumanImageImage AnalysisInvasive LesionLight MicroscopeLungLung AdenocarcinomaLung NeoplasmsMachine LearningMalignant NeoplasmsMalignant neoplasm of lungMicroscopyMolecularMolecular StructureMorbidity - disease rateMusNormal CellNormal tissue morphologyOpticsParaffin EmbeddingPathologistPathway interactionsPatientsPreparationPreventionPrognosisProtocols documentationRecommendationResearchResolutionRiskRisk AssessmentRisk FactorsSamplingScreening for cancerSensitivity and SpecificitySmokerSmokingSpecimenSputumStructureStructure of parenchyma of lungSystemTechniquesTimeTissuesTobacco-Associated CarcinogenTrainingUnited StatesVisualizationbronchial epitheliumcancer cellcarcinogenesiscigarette smokingclinical imagingclinically significantcohortcommunity based researchcost effectivedetection methodformer smokerhigh resolution imaginghigh riskimaging systemimprovedinnovationinnovative technologieslight microscopylow dose computed tomographylung cancer screeninglung carcinogenesislung developmentmolecular scalemortalitymouse modelnanometer resolutionnanoscaleneoplasticnon-smokernovel strategiesprogramsrepositorysample collectionscreeningsingle moleculesuccesssuperresolution imagingsuperresolution microscopytumortumor progression
项目摘要
PROJECT SUMMARY/ABSTRACT
Lung cancer is the leading cause of cancer-related death in the United States. Overall, patients diagnosed with
early-stage lung cancer have a much better prognosis. Cigarette smoking is the major cause of lung cancer
and screening for lung cancer is currently recommended for high-risk current and former smokers. Compared
with nonsmokers, smokers have an almost 30-fold increased risk of developing lung cancer. Unfortunately,
despite significant efforts, early detection of lung cancer remains sub-optimal with conventional approaches
suffering from high false-positive rates or limited sensitivity. Improved understanding of the early events
underlying smoking-related lung cancer development is crucial to the identification of new biomarkers and
targets for early detection and prevention. Further, new methods that detect those early events in lung cancer
development in a non-invasive and cost-effective manner with high sensitivity and specificity are urgently
needed. Recent advances in super-resolution microscopy revolutionize the field of optical microscopy and offer
a new ability to visualize molecular structure at nanometer resolution that is invisible under a conventional light
microscope. We propose an innovative approach to adapt super-resolution microscopy to improve the early
detection of lung cancer. Our approach is built upon our recent discovery that chromatin folding becomes
gradually fragmented in early lung carcinogenesis, even when cells still appear normal under conventional light
microscope. Our ultimate goal is to detect such nanoscale chromatin “misfolding” in bronchial cells present in
sputum to improve early detection of lung cancer. In this project, we will first establish disrupted nanoscale
chromatin folding as an early event in lung carcinogenesis utilizing a mouse model of carcinogen-induced lung
adenocarcinoma as well as existing well-annotated human lung tissue specimens (Aim 1). In addition, we will
evaluate the feasibility of super-resolution imaging of nanoscale chromatin “misfolding” for early detection of
lung cancer using existing sputum samples and data from the Pittsburgh Lung Screening Study, a community-
based research cohort of current and ex-smokers, screened with low-dose computed tomography and followed
for lung cancer (Aim 2).
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Laura P. Stabile其他文献
Laura P. Stabile的其他文献
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{{ truncateString('Laura P. Stabile', 18)}}的其他基金
(PQA2) Elucidating the link between obesity, inflammation and estrogen signaling
(PQA2) 阐明肥胖、炎症和雌激素信号传导之间的联系
- 批准号:
8683852 - 财政年份:2014
- 资助金额:
$ 18.21万 - 项目类别:
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