Genetics and Genomics

遗传学和基因组学

• 批准号: 10398063
• 负责人: John J. Krolewski
• 金额: $ 4.45万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-06-16 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10398063
• 关键词: Address; African American population; Applications Grants; Area; Basic Science; Big Data; Bioinformatics; Biological Markers; Biometry; CDK4 gene; Cancer Center Support Grant; Cancer Etiology; Catchment Area; Cell Cycle Regulation; Cells; Clinical; Collaborations; Complement; Cytokine Signaling; DNA Methylation; Data Analyses; Dependence; Development; Direct Costs; Disease; Disease Progression; Doctor of Philosophy; Endocrine; Epigenetic Process; Etiology; Event; Funding; Future; Gene Expression; Genes; Genetic; Genetic Transcription; Genets; Genitourinary system; Genome; Genome Stability; Genomics; Goals; Hormones; Journals; Knowledge; Leadership; Malignant Neoplasms; Malignant neoplasm of gastrointestinal tract; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Malignant neoplasm of prostate; Medicine; Methods; Modeling; Molecular; Molecular Diagnosis; Molecular and Cellular Biology; Nuclear Receptors; Oncogenes; Outcome; Pathology; Pathway interactions; Patients; Peer Review; Pharmaceutical Preparations; Pharmacology; Phenotype; Population; Productivity; Publications; Recurrent disease; Refractory; Research; Research Personnel; Resistance; Role; SETDB1 gene; Science; Signal Pathway; Site; Strategic vision; The Sun; Therapeutic; Therapeutic Intervention; Therapeutic Trials; Thoracic Surgical Procedures; Translating; Translational Research; Tumor Biology; Tumor Suppressor Genes; Tumor Suppressor Proteins; Tumor Tissue; Urology; Work; arm; cancer genetics; cancer genomics; cancer therapy; chromatin modification; clinical application; clinical development; clinical diagnostics; cohort; data hub; experience; gene discovery; genome sciences; genomic locus; innovation; insight; interest; investigator-initiated trial; malignant breast neoplasm; member; molecular diagnostics; novel; personalized approach; personalized intervention; personalized medicine; precision medicine; precision oncology; programs; progression marker; prospective; prostate cancer progression; recruit; replication stress; response; targeted treatment; therapeutic target; therapy development; tool; translational cancer research; tumor; tumorigenic

The overall goal of the Genetics and Genomics (GG) Program is to discover novel cancer genes, to elucidate the function of diverse genetic and epigenetic states, to translate mechanistic insight into therapeutic targets and associated biomarkers, and to accelerate the delivery of precision cancer medicine to our patients. This will be accomplished in three aims: Aim 1 – To interrogate genetic drivers of tumor hallmarks; Aim 2 – To delineate epigenetic states as biomarkers and targets in cancer, and Aim 3 – To translate of genetic and epigenetic discovery toward clinical application. A number of important scientific discoveries emanated from the GG Program that illustrate the overall research depth, cancer focus, and added value. Additionally, the GG Program developed unique tumor sequencing data and analysis approaches to support precision medicine concepts. For example, panels developed within the GG Program were leveraged toward the development of a molecular diagnostic company (OmniSeq) that contributes to the recruitment of Roswell Park patients into molecular basket trials, such as NCI-MATCH. The GG Program research portfolio encompasses studies addressing genetic basis of aggressiveness of hormone refractory breast and prostate cancer in African- American populations – cancers that are of particular importance for our WNY catchment area. John Krolewski, MD, PhD and Erik Knudsen, PhD are new co-Leaders for the Program who have strong interests in basic, clinical, and population aspects of tumor genetics and epigenetics. Dr. Krolewski's leadership efforts focus on signaling/cytokine pathways and genomics of genitourinary malignancies, which complements Dr. Knudsen's focus in the areas of cell cycle control and genomic stability, and targeting such pathways in breast and gastrointestinal cancers. The Program is comprised of 27 members from nine Roswell Park departments/centers (Cancer Genetics and Genomics, Center for Personalized Medicine, Molecular and Cellular Biology, Pharmacology and Therapeutics, Urology, Thoracic Surgery, Biostatistics and Bioinformatics, Medicine, and Pathology), whose total peer-reviewed funding is $3.1M direct costs (NCI funding $1.9M direct) and a total funding of $5.4M direct costs. Since the last renewal, 12 new members (nine recruited from outside Roswell Park) have joined the Program. Of the 385 publications generated over the last funding cycle, 9% are intra-programmatic and 44% are inter-programmatic; 50 (13%) publications are in journals with an impact factor >10. Future goals of the Program are focused on multi-investigator projects that make impactful discoveries and translate basic science into the clinical arena, harnessing GG science to target cancers at the genetic and epigenetic levels.

遗传学和基因组学（GG）计划的总体目标是发现新的癌症基因， 阐明不同的遗传和表观遗传状态的功能，将机械的见解转化为治疗 靶点和相关的生物标志物，并加速向我们的患者提供精确的癌症药物。 这将在三个目标中实现：目标1 -询问肿瘤标志物的遗传驱动因素;目标2 - 将表观遗传状态描述为癌症中的生物标志物和靶点，目标3 -将遗传和 表观遗传学发现走向临床应用。许多重要的科学发现都来自于 GG计划说明了整体研究深度，癌症重点和附加值。此外，GG 该计划开发了独特的肿瘤测序数据和分析方法，以支持精准医疗 理念的例如，在GG计划内开发的面板被用于开发 分子诊断公司（OmniSeq），有助于招募罗斯韦尔公园患者进入 分子篮试验，如NCI-MATCH。GG计划的研究组合包括研究 解决非洲激素难治性乳腺癌和前列腺癌侵袭性的遗传基础- 美国人口-癌症是我们的WNY集水区特别重要。 John Krolewski，MD，PhD和Erik Knudsen，PhD是该计划的新共同领导人，他们拥有强大的 对肿瘤遗传学和表观遗传学的基础、临床和人群方面感兴趣。克劳莱斯基医生 领导层的工作重点是信号/细胞因子途径和泌尿生殖系统恶性肿瘤的基因组学， 补充了Knudsen博士在细胞周期控制和基因组稳定性领域的重点，并针对这些领域， 乳腺癌和胃肠癌的通路。该计划由来自9个罗斯韦尔的27名成员组成 公园部门/中心（癌症遗传学和基因组学，个性化医学中心，分子和 细胞生物学，药理学和治疗学，泌尿外科，胸外科，生物统计学和生物信息学， 医学和病理学），其同行评审资金总额为310万美元直接成本（NCI直接资金为190万美元） 以及540万美元的直接成本。自上次延长任期以来，12名新成员（9名从外部征聘） 罗斯韦尔公园）已加入该计划。在上一个供资周期产生的385份出版物中， 方案内出版物和44%的方案间出版物; 50份（13%）出版物发表在具有影响因子的期刊上 >10.该计划的未来目标集中在多研究者项目，使有影响力的发现 并将基础科学转化为临床竞技场，利用GG科学将癌症靶向遗传和 表观遗传水平