BLR&D Research Career Scientist Award Application

BLR

• 批准号: 10047723
• 负责人: RAJVIR DAHIYA
• 金额: --
• 依托单位: VETERANS AFFAIRS MED CTR SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-10-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10047723
• 关键词: 5' Untranslated Regions; Address; African American; Area; Asians; Assessment tool; Award; Basic Science; Biological Markers; Biotechnology; Bladder; Cancer Detection; Cancer Patient; Cancer Prognosis; Caucasians; Cause of Death; Cell Death; Cells; Clinical; Clinical Research; Clinical assessments; Collaborations; Communities; DNA Methylation; Databases; Diagnosis; Diagnostic; Diet; Double-Stranded RNA; E-Cadherin; Epigenetic Process; Estrogen Receptors; Estrogens; Event; FDA approved; Faculty; Funding; Gene Activation; Gene Amplification; Gene Expression; Genes; Genetic; Genetic Markers; Genetic Polymorphism; Genistein; Goals; Healthcare Systems; Hypermethylation; Incidence; Institution; Intervention; Journals; Kidney; Laboratories; Legal patent; Link; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Malignant neoplasm of urinary bladder; Methylation; MicroRNAs; Mission; Molecular; Molecular Genetics; Mutation; National Institute of Diabetes and Digestive and Kidney Diseases; Nature; Neoplasm Metastasis; Nucleic Acids; Oncogenes; Oncogenic; Pathway interactions; Peer Review; Pharmacologic Substance; Play; Procedures; Prognosis; Prognostic Marker; Promoter Regions; Prostate; Prostate Cancer therapy; Publications; Publishing; RNA; Race; Regulation; Renal carcinoma; Reporting; Research; Research Personnel; Resources; Risk Assessment; Risk Factors; Role; Science; Scientist; Single Nucleotide Polymorphism; System; Training; Tumor Antigens; Tumor Suppressor Genes; Tumor Suppressor Proteins; United States Department of Veterans Affairs; United States National Institutes of Health; Untranslated RNA; Urologic Cancer; Veterans; Work; anticancer research; base; c-myc Genes; cancer biomarkers; cancer diagnosis; carcinogenesis; career; chromatin remodeling; diagnostic biomarker; differential expression; health disparity; high risk; histone modification; member; molecular marker; overexpression; prognostic significance; programs; promoter; prostate cancer metastasis; prostate cancer progression; risk variant; silibinin; soy; urologic

Prostate, kidney and bladder cancers (urological malignancies) are the most common cause of death among our Veterans. Therefore, there is an urgent unmet need for the management of these malignancies. To address these issues, the applicant has been working in the field of urological malignancies since 1987. There are three main goals of the applicant's research: 1) To investigate the molecular mechanisms of initiation, progression and metastasis of urological malignancies. 2) To identify molecular biomarkers for diagnosis and prognosis of urological cancers. 3) Treatment of urological cancers using natural compounds. To accomplish these goals, the applicant has received several VA and NIH funded projects in collaboration with VA and Non-VA clinicians and scientists. The applicant has been very productive with 350 scientific publications in peer-reviewed journals and has had a distinguished career for 27 years in the VA system. Throughout his career, he has been at the forefront of research into the molecular mechanisms of urological cancers. His research work is supported by several NIH/VA funded projects and currently, he has one VA Merit Review award and two NIH funded RO1 projects. He has trained more than 50 fellows and most of them are faculty members at various institutions with funded research programs. The applicant has extensively collaborated with VA investigators and non-VA investigators in funded program projects and scientific publications. The applicant was the first one to receive a REAP (Research Enhancement Award Program) on prostate cancer from the Department of Veterans Affairs (PI: Dahiya, 1999-2012). He has trained several scientists in collaboration with VA clinician scientists. Recently, the applicant received a VA program project on the “Role of genetic biomarkers in clinical assessment of prostate cancer” (PIs: Dahiya, Tanaka, Lau, 10-2012-09-2017) in collaboration with four VA scientists and clinicians. Under this program, his team has investigated whether SNPs, CpG methylation, miRNAs and X-linked genes together can predict which localized prostate cancer patients have a higher risk of developing metastasis and thus require more aggressive interventions. Currently, the applicant has a VA Merit Review award “ Regulation of c-Myc/HIF pathway in the management of kidney cancer” (PI: Dahiya, 10/2011-09/2020) and two NIH RO1 projects UO1CA184966 “Genetic factors for race related prostate cancer” (PI: Dahiya 07/2015-06/2020) and RO1CA199694 “Molecular biomarkers for kidney cancer prognosis using non-coding RNAs (PI: Dahiya 06/2016-05/2021) In summary, the applicant's scientific contributions are vitally important to the VA mission. He has made ground breaking discoveries in the field of urological cancers and has also provided significant resources to the scientific community and the VA system. The applicant's laboratory has made several significant contributions to the fields of epigenetics (DNA methylation, histone modification, chromatin remodeling), non-coding RNAs (dsRNA, miRNAs), SNPs of various genes and their roles in diagnosis, prognosis, progression, metastasis and risk assessment and treatment of urological malignancies. These are high priority programs for our VA health care system.

前列腺癌、肾癌和膀胱癌（泌尿系统恶性肿瘤）是最常见的 我们退伍军人的死亡原因。因此，迫切需要满足未满足的需求 管理这些恶性肿瘤。为了解决这些问题，申请人一直致力于 自1987年以来一直致力于泌尿系统恶性肿瘤领域。申请人的三个主要目标 研究：1）研究起始、进展和转移的分子机制 泌尿系统恶性肿瘤。 2）确定用于诊断和预后的分子生物标志物 泌尿系统癌症。 3) 使用天然化合物治疗泌尿系统癌症。为了完成 为了实现这些目标，申请人已获得多个 VA 和 NIH 资助的项目 VA 和非 VA 临床医生和科学家。 申请人的成果非常丰富，发表了 350 篇经过同行评审的科学出版物 期刊，并在 VA 系统中拥有 27 年的杰出职业生涯。在他的整个职业生涯中， 他一直处于泌尿系统癌症分子机制研究的前沿。他的 研究工作得到了多个 NIH/VA 资助项目的支持，目前，他拥有一项 VA 优异奖 评审奖和两个 NIH 资助的 RO1 项目。他培训过 50 多名研究员，其中大多数 其中包括拥有资助研究项目的各个机构的教职人员。 申请人与 VA 研究人员和非 VA 研究人员广泛合作 在资助的计划项目和科学出版物中。申请人是第一个收到的 来自卫生部的一项关于前列腺癌的 REAP（研究增强奖计划） 退伍军人事务部（PI：Dahiya，1999-2012）。他与以下机构合作培训了几位科学家 VA 临床医生科学家。 近日，申请人收到VA项目“遗传生物标志物的作用” 前列腺癌的临床评估”（PI：Dahiya、Tanaka、Lau，10-2012-09-2017） 与四位退伍军人管理局科学家和临床医生合作。根据该计划，他的团队调查了 SNP、CpG 甲基化、miRNA 和 X 连锁基因一起能否预测哪些基因 局限性前列腺癌患者发生转移的风险较高，因此需要 更积极的干预措施。 目前，申请人已获得 VA 优异评审奖“Regulation of c-Myc/HIF Pathway” 肾癌管理”（PI：Dahiya，10/2011-09/2020）和两个 NIH RO1 项目 UO1CA184966“种族相关前列腺癌的遗传因素”（PI：Dahiya 07/2015-06/2020） 和 RO1CA199694“使用非编码 RNA 进行肾癌预后的分子生物标志物 （PI：达希亚 06/2016-05/2021） 总之，申请人的科学贡献对于 VA 的使命至关重要。 他在泌尿系统癌症领域取得了突破性的发现，并提供了 为科学界和 VA 系统提供重要资源。申请人实验室 在表观遗传学领域做出了多项重大贡献（DNA甲基化、组蛋白 修饰、染色质重塑）、非编码 RNA（dsRNA、miRNA）、各种 SNP 基因及其在诊断、预后、进展、转移和风险评估中的作用以及 泌尿系统恶性肿瘤的治疗。这些是我们 VA 医疗保健的高度优先计划 系统。

项目成果

PHGDH as a Key Enzyme for Serine Biosynthesis in HIF2α-Targeting Therapy for Renal Cell Carcinoma.

• DOI: 10.1158/0008-5472.can-17-1589
• 发表时间: 2017-11-15
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Yoshino H;Nohata N;Miyamoto K;Yonemori M;Sakaguchi T;Sugita S;Itesako T;Kofuji S;Nakagawa M;Dahiya R;Enokida H
• 通讯作者: Enokida H

Suppressor effect of catechol-O-methyltransferase gene in prostate cancer.

• DOI: 10.1371/journal.pone.0253877
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Hashimoto Y;Shiina M;Maekawa S;Kato T;Shahryari V;Kulkarni P;Dasgupta P;Yamamura S;Saini S;Tabatabai ZL;Dahiya R;Tanaka Y
• 通讯作者: Tanaka Y

MicroRNA-466 inhibits tumor growth and bone metastasis in prostate cancer by direct regulation of osteogenic transcription factor RUNX2.

• DOI: 10.1038/cddis.2017.15
• 发表时间: 2017-01-26
• 期刊: Cell death & disease
• 影响因子: 9
• 作者: Colden M;Dar AA;Saini S;Dahiya PV;Shahryari V;Yamamura S;Tanaka Y;Stein G;Dahiya R;Majid S
• 通讯作者: Majid S

Role of the PI3K/Akt pathway in cadmium induced malignant transformation of normal prostate epithelial cells.

• DOI: 10.1016/j.taap.2020.115308
• 发表时间: 2020-12-15
• 期刊: Toxicology and applied pharmacology
• 影响因子: 3.8
• 作者: Kulkarni P;Dasgupta P;Bhat NS;Hashimoto Y;Saini S;Shahryari V;Yamamura S;Shiina M;Tanaka Y;Dahiya R;Majid S
• 通讯作者: Majid S

Elevated miR-182-5p Associates with Renal Cancer Cell Mitotic Arrest through Diminished MALAT-1 Expression.

• DOI: 10.1158/1541-7786.mcr-17-0762
• 发表时间: 2018-11
• 期刊: Molecular cancer research : MCR
• 作者: Kulkarni P;Dasgupta P;Bhat NS;Shahryari V;Shiina M;Hashimoto Y;Majid S;Deng G;Saini S;Tabatabai ZL;Yamamura S;Tanaka Y;Dahiya R
• 通讯作者: Dahiya R