BLR&D Research Career Scientist Award Application
BLR
基本信息
- 批准号:10293583
- 负责人:
- 金额:--
- 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
- 起止时间:2019-10-01 至 2024-09-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAlzheimer&aposs DiseaseAnimal ModelAwardBacteriaBindingBioinformaticsBiological MarkersBiologyCDC2 geneCaliforniaCardiovascular DiseasesCardiovascular systemCell ProliferationCellsChromosomesChromosomes, Human, YClinicalClinical ManagementCloningCloning VectorsCodeCollaborationsCyclin BDNA LibraryDatabasesDevelopmentDiagnosisDiseaseDisease ProgressionEctopic ExpressionEducational workshopElderly manEmbryoEpithelial CellsEquipmentFamilyFeedbackFoundationsFundingGenesGeneticGenetic MaterialsGenetic ModelsGenetic Predisposition to DiseaseGenetic TranscriptionGenomeGenomic InstabilityGenomicsGonadal structureGonadoblastomaHealthHealth Services ResearchHealthcareHealthcare SystemsHepatocyteHistonesHomologous GeneHormone ReceptorHumanHuman GenomeImmunologic SurveillanceImpairmentIncidenceInstitutesInternationalJournalsKnowledgeLaboratoriesLaboratory FindingLinkLysineMalignant NeoplasmsMalignant neoplasm of liverMalignant neoplasm of lungMalignant neoplasm of prostateMammalian CellMapsMediatingMedicalMethodsMolecularMolecular GeneticsMosaicismMyocardial InfarctionNatureNeurodegenerative DisordersOncogenesOncogenicOutcomePharmaceutical PreparationsPhysiologyPilot ProjectsPopulationPredispositionPrognosisPropertyProstateProteinsProto-OncogenesPublishingRecombinant DNAReportingResearchResearch PersonnelRiskRoleSan FranciscoScienceScientistScreening procedureSeriesSex ChromosomesSex DifferencesSignal PathwaySomatic CellStem Cell FactorSystemTK GeneTSPY1 geneTechniquesTechnologyTestingTestisTherapeuticTimeTissuesTransactivationTransgenesTransgenic MiceTreatment outcomeTumor Suppressor ProteinsUnited States National Academy of SciencesUniversitiesValidationVariantVeteransWorkX ChromosomeY Chromosomeauthoritybasecareerchromosome Y lossdesigndifferential expressiondosageeffective therapyexperimental studygender disparitygermline stem cellshealth care deliveryhuman diseasehuman modelimprovedinsightinterestlung developmentmalemale sex hormonesmembermenmortalitymouse modelneurogenesisnew technologynext generation sequencingnon-alcoholic fatty liver diseaseperipheral bloodpostnatalprecision medicineprofessorprogramsresearch and developmentsexsex determinationsexual dimorphismsry Genestargeted treatmenttherapeutic targettooltranscription factortranslational applicationstranslational potentialtreatment planningtreatment responsetumorigenesis
项目摘要
Dr. Lau is an internationally recognized investigator in the Y chromosome biology and an established
expert in molecular genetics and transgenic mouse modeling of human diseases. He has established various
molecular tools in his laboratory, installed advanced next generation sequencing equipment and bioinformatics
in the Molecular Core, and served as consultant for PIs interested in such advanced technologies at the SFVA.
Currently, he has several established and pilot projects. First project focuses on the roles of the Y-located
proto-oncogene TSPY in liver and prostate cancers. TSPY is the gene for the gonadoblastoma locus on the Y
chromosome (GBY), the only oncogenic locus on this male-specific chromosome. Normally, it functions as a
male germ stem cell factor, but as an oncogene when ectopically expressed in somatic cells, such as prostate
epithelial cells and hepatocytes. It stimulates cell proliferation and cyclin B-CDK1 kinase activities. TSPY forms
a positive feedback loop with male sex hormone receptor AR and constitutively active variant AR-V7, thereby
amplifying their respective oncogenic actions. Research centers on exploring the correlation between TSPY,
AR/AR-V7 expression and clinical features and outcomes in liver and prostate cancers; and on studying
experimentally the contributions of TSPY and AR/AR-V7 in oncogenesis in liver and prostate cancer. Validation
of the roles of TSPY in AR/AR-V7 in the male-dominance in liver cancer could offer immediate translational
applications of effective anti-AR/AR-V7 drugs already developed for prostate cancer to the treatment of liver
cancer. The second project focuses on the X-located homologue of TSPY, TSPX on human oncogenesis. Due
to evolutionary divergence, TSPX possesses contrasting properties, i.e. retards cell proliferation, inhibits cyclin
B-CDK1 and AR/AR-V7 transactivation activities, and behaves as a tumor suppressor in various cancers,
including lung, liver and prostate cancers. Studies are designed to identify their respective oncogenic and
tumor suppressor domains, and signaling pathways in oncogenesis. The third project focuses on the genes on
the male-specific region of the Y chromosome (MSY) in sex differences in various physiology and diseases.
The current emphasis is on the sex-determining gene SRY, which is essential for sex determination, but not for
the development of non-gonadal tissues. Dr. Lau has established an efficient transgene activation system and
demonstrated that aberrant expression of a human SRY induces various abnormalities in transgenic mice,
including retardation in neurogenesis and postnatal lung development, nonalcoholic fatty liver disease and
myocardial infarction. Studies are being conducted to characterize the mechanisms of diseases, mediated by
aberrant SRY expression in the respective tissues. The fourth project focuses on the recently observed link
between mosaic loss of the Y chromosome (mLOY) in the peripheral blood and increased risks and mortality in
elderly men. In collaborations with Health Research scientists at SFVA, Dr. Lau plans to explore the possibility
of using mLOY as screening tool for cancers and cardiovascular and neurodegenerative diseases among the
Veterans, such as the databases of the Million Veteran Program (MVP). He hypothesizes that mLOY results in
dosage unbalance of the highly conserved X-Y homologous genes, such as the histone lysine demethylases
SMCY and UTY, resulting in deficiency in immunosurveillance and predisposition of affected tissues to disease
development. He will use transgenic mouse models to evaluate such genetic predisposition, characterize them
with advanced genomics and bioinformatics techniques and correlate the results with clinical observations.
Dr. Lau is a key and contributing member of the SFVA. He has developed a continuously funded
research program using advanced molecular genetics, genomics, bioinformatics and transgenic mouse
approaches. His research has provided useful biomarkers for precise diagnosis, prognosis, and targets for
therapeutics; and the scientific supports for sex differences and disease mechanisms, essential in establishing
the precision medicine for the efficient and effective deliveries of healthcare for our Veterans.
刘博士是国际公认的Y染色体生物学研究者,并建立了
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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YUN-FAI CHRIS LAU其他文献
YUN-FAI CHRIS LAU的其他文献
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{{ truncateString('YUN-FAI CHRIS LAU', 18)}}的其他基金
Molecular Mechanisms of a Male-Specific Positive Feedback Loop in Liver Cancer
肝癌男性特异性正反馈环的分子机制
- 批准号:
10202474 - 财政年份:2019
- 资助金额:
-- - 项目类别:
ShEEP Request for Single-Cell Next-Generation Sequencing Library Preparation System
ShEEP 请求单细胞下一代测序文库制备系统
- 批准号:
9906732 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Role of the Y-Located TSPY Gene in Human Oncogenesis
Y 定位的 TSPY 基因在人类肿瘤发生中的作用
- 批准号:
8196347 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Role of the Y-Located TSPY Gene in Human Oncogenesis
Y 定位的 TSPY 基因在人类肿瘤发生中的作用
- 批准号:
8391614 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Sex Chromosomes and Gender Disparity in HBV-Related Hepatocellular Carcinoma
HBV 相关肝细胞癌中的性染色体和性别差异
- 批准号:
8116508 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Role of the Y-Located TSPY Gene in Human Oncogenesis
Y 定位的 TSPY 基因在人类肿瘤发生中的作用
- 批准号:
7931856 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Role of the Y-Located TSPY Gene in Human Oncogenesis
Y 定位的 TSPY 基因在人类肿瘤发生中的作用
- 批准号:
8597395 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Sex Chromosomes and Gender Disparity in HBV-Related Hepatocellular Carcinoma
HBV 相关肝细胞癌中的性染色体和性别差异
- 批准号:
7977982 - 财政年份:2010
- 资助金额:
-- - 项目类别: