Impact of age on altered steroidogenesis and estrogen receptor activation in benign prostatic hyperplasia progression
年龄对良性前列腺增生进展中类固醇生成改变和雌激素受体激活的影响
基本信息
- 批准号:10610847
- 负责人:
- 金额:$ 13.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-05-15 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAgeAgingAndrogensAnimal ModelApoptosisAreaBenign Prostatic HypertrophyBiological AssayBiological MarkersCRISPR/Cas technologyCatabolismCell LineChromatinClinicalCombined Modality TherapyComplexDNA MethylationDataDevelopmentDiseaseDisease ProgressionDisease stratificationElementsEnvironmentEnzymesEpigenetic ProcessEquilibriumEstrogen Receptor alphaEstrogen Receptor betaEstrogen ReceptorsEstrogensEtiologyFunctional disorderGene ExpressionGenesGlycolsGoalsGonadal Steroid HormonesGrantHomeostasisHormone ReceptorHormonesHumanHyperplasiaImmunohistochemistryIn VitroIncreased frequency of micturitionKnockout MiceLigandsLower urinary tractMapsMediatingMentorsMetabolismMethodsMethylationModelingModificationMolecularMonitorMusPatientsPeripheralPharmaceutical PreparationsPharmacotherapyPositioning AttributeProductionProliferatingProstateProstatic DiseasesQuality of lifeReceptor ActivationResearchResearch PersonnelResolutionSamplingSelective Estrogen Receptor ModulatorsSignal TransductionStanoloneSteroid biosynthesisSteroidsSymptomsTestingTestosteroneTissuesTrainingTreatment CostTreatment EffectivenessTreatment EfficacyUniversitiesUrologic DiseasesWisconsinWorkage effectage relatedagedandrogen biosynthesisbiomarker identificationbisulfite sequencingcareercareer developmentchromatin remodelingclinical efficacyclinical examinationdesigneffective therapyeffectiveness evaluationepigenetic regulationexperiencegain of functiongenome-widehormone regulationimprovedin vivoinsightloss of functionlower urinary tract symptomsmalemenminimally invasivemolecular modelingmouse modelnovelnovel drug combinationoxysterol 7-alpha-hydroxylasepromoterprototypereceptorreceptor expressionsteroid hormonesteroid hormone metabolismsteroid hormone receptorsteroid metabolismtherapy resistanturinary
项目摘要
Project Summary/Abstract
Candidate: My overall career goal is to become an independent investigator and leader in an aging
related field focused on urologic diseases, especially lower urinary tract dysfunction (LUTD). Benign
prostatic hyperplasia (BPH) is a disease that primarily affects aging men and manifests as urinary dysfunction.
However, the etiology of the disease is complex and multifactorial and the impact of aging on the hormone
environment is often not considered in current research. The overarching goal of my work is to examine the
effects of aging on sex steroid hormones that contribute to the development of disease and identify biomarkers
relevant to disease progression and treatment efficacy. The goal of this K01 career development proposal is to
provide me with the research experience and training needed to become an independent investigator and
leader in the field. My training will be targeted to three key areas: 1) molecular modeling of aging and disease,
2) identification and analysis of peripheral biomarkers, and 3) epigenetic modifiers of the aging steroid
hormone environment. This research experience combined with the mentoring from leading experts at the
University of Wisconsin – Madison will uniquely position me for a successful independent research career.
Research: Benign prostatic hyperplasia (BPH) impacts 50% of men in their 50s but dramatically increases to
90% of men in their 80s with annual treatment costs $4 billion. One consequence of aging in males is altered
steroid hormone synthesis and metabolism that leads to elevated levels of circulating estrogens. Estrogen
signaling through estrogen receptors (ER) within the prostate regulate prostate tissue homeostasis with ERα
associated with proliferation and ERβ with apoptosis. Current BPH treatments target the biosynthesis of
androgens with little consideration for androgen conversion to ER ligands. I hypothesize that selective ER
modulators (SERMs) can reestablish ERα:ERβ homeostasis through ERβ activation and reverse the
impact of ERα-mediated proliferation on BPH progression in the aging male. The critical elements of this
hypothesis will be tested in the following specific aims:
Aim 1: Determine the impact of age-related changes in steroidogenic enzymes required for ERβ ligand
production on prostate proliferation in vitro and in vivo.
Aim 2: Examine the effect of aging on the epigenetic regulation of steroid hormone metabolism and activity.
Aim 3: Evaluate the effectiveness of SERMs to limit hyperplasia in the aging prostate.
The work proposed in these aims is designed to identify potential peripheral biomarkers to aid in assessing and
stratifying BPH patients with age-associated hormone driven hyperplasia. This will allow for the development of
novel combination pharmacotherapies that would enhance the clinical efficacy of current drug treatments.
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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Teresa Liu的其他文献
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{{ truncateString('Teresa Liu', 18)}}的其他基金
Impact of age on altered steroidogenesis and estrogen receptor activation in benign prostatic hyperplasia progression
年龄对良性前列腺增生进展中类固醇生成改变和雌激素受体激活的影响
- 批准号:
9976945 - 财政年份:2020
- 资助金额:
$ 13.1万 - 项目类别:
Impact of age on altered steroidogenesis and estrogen receptor activation in benign prostatic hyperplasia progression
年龄对良性前列腺增生进展中类固醇生成改变和雌激素受体激活的影响
- 批准号:
10392989 - 财政年份:2020
- 资助金额:
$ 13.1万 - 项目类别:
Impact of age on altered steroidogenesis and estrogen receptor activation in benign prostatic hyperplasia progression
年龄对良性前列腺增生进展中类固醇生成改变和雌激素受体激活的影响
- 批准号:
10161707 - 财政年份:2020
- 资助金额:
$ 13.1万 - 项目类别:
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