The tumor suppressor capability of p53 is dependent on Non-muscle Myosin IIA function in Head and Neck Cancer.

p53 的肿瘤抑制能力依赖于头颈癌中的非肌肉肌球蛋白 IIA 功能。

• 批准号: 9346608
• 负责人: David M. Neskey
• 金额: $ 13.5万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-06 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9346608
• 关键词: Address; Advisory Committees; Applications Grants; Area; Award; Biology; Cancer Center; Candidate Disease Gene; Caring; Cell Line; Cells; Characteristics; Classification; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Committee Members; Complement; DNA Sequence Alteration; Data; Disease; Disease Progression; Ensure; Environment; Event; Functional disorder; Funding; Future; Gene Activation; Gene Targeting; Genes; Genetic; Goals; Guide RNA; Head and Neck Cancer; Head and Neck Neoplasms; Head and Neck Squamous Cell Carcinoma; Investigation; Knowledge; Laboratories; Lead; Malignant Epithelial Cell; Malignant Neoplasms; Mediating; Medical; Mentors; Mentorship; Methodology; Modeling; Mutate; Mutation; Myosin Heavy Chains; Neoplasm Metastasis; Nonmuscle Myosin Type IIA; Normal Cell; Oncogenic; Otolaryngology; Outcome; Pathway interactions; Patient-Focused Outcomes; Patients; Pharmacology; Phenotype; Positioning Attribute; Proteins; Public Health; Research; Research Activity; Research Personnel; Research Project Grants; Research Training; Risk; Role; Scientist; Solid; South Carolina; Surgeon; TP53 gene; Technology; Testing; Therapeutic Intervention; Time; Translating; Tumor Cell Invasion; Tumor Suppressor Genes; Tumor Suppressor Proteins; Tumorigenicity; United States; Universities; Work; base; cancer diagnosis; carcinogenesis; career; cell motility; clinical practice; endonuclease; head and neck cancer patient; high risk; improved; improved outcome; in vivo; malignant mouth neoplasm; migration; molecular marker; mutant; neoplastic cell; non-muscle myosin; novel; overexpression; programs; survival outcome; targeted treatment; tool; transcriptome sequencing; treatment strategy; tumor; vector

PROJECT SUMMARY / ABSTRACT Dr. Neskey's short-term goals are to obtain outstanding research training in methodological, conceptual and theoretical approaches to laboratory-based scientific investigation which will help him determine the role of non-muscle Myosin IIA (NMIIA) in regulating p53 as a tumor suppressor in head and neck cancer. The K08 Award will enable him to further mature as a scientist, and develop the skillset, tools, knowledge, and expertise to excel in the scientific arena. It is anticipated that during the K08 funding period he will be well positioned to submit a Research Project Grant (R01) application, representing the natural progression of his research activities from this K08 grant proposal. Dr. Neskey's long-term career objective is to spearhead an independently funded, comprehensive research program as a surgeon-scientist exploring the mechanisms of tumor cell invasion and metastasis that complements and enhances his clinical practice focused on the care of head and neck cancer patients. Ultimately, discoveries from his laboratory will be translated to the clinical realm with the goal of improving outcomes of patients suffering from oral cancer. In order to achieve his career goals, Dr. Neskey has partnered with Drs. Rosenzweig, Watson, and Garrett- Mayer for scientific mentorship. Each committee member has an established record as a mentor and an independent investigator. In addition to the strong mentoring committee, the Departments of Otolaryngology and Pharmacology at the Medical University of South Carolina along with Hollings Cancer Center have provided protected time, laboratory space, and a significant start up package the ensure a solid and productive research environment. Dr. Neskey has also developed an external advisory committee comprised of two of previous mentors, Drs. Jeffrey Myers and Cynthia Morton who provide additional expertise in the fields of p53 biology and tumor genetics respectively which will complement his MUSC based mentoring committee. Head and neck cancer accounts for over 60,000 new cancer diagnoses annually in the U.S. with 25-30% of patients ultimately dying from their disease, which suggests a significant need for continued research to identify factors contributing to poor outcomes in these patients. A promising area of research is high-risk mutations in the tumor suppressor gene, TP53, which are associated with decreased survival and are harbored in approximately 50% of these cancers. To date, it is not currently understood how these mutations make head and neck tumor cells more invasive. The studies described in this proposal will directly address the role of non- muscle Myosin IIA in the tumor suppressor capability of mutant TP53 in head and neck cancer and demonstrate NMIIA dysfunction results in characteristics of high-risk mutant p53 including increased cell invasion and tumor formation. Ultimately, this research could lead to precise therapies targeting these aggressive tumors and subsequently improving the survival of patients with head and neck cancer.

项目摘要/摘要 博士Neskey的短期目标是在方法论、概念和 理论方法，以实验室为基础的科学研究，这将有助于他确定的作用， 非肌肉肌球蛋白IIA（NMIIA）在调节p53作为肿瘤抑制因子在头颈癌。K08 该奖项将使他能够进一步成熟为一名科学家，并发展技能、工具、知识和专业知识 在科学竞技场中出类拔萃。预计在K 08融资期间，他将处于有利地位， 提交研究项目资助（R 01）申请，代表其研究的自然进展 这是K 08计划的一部分。Neskey博士的长期职业目标是带头 独立资助的，全面的研究计划，作为外科医生，科学家探索的机制， 肿瘤细胞的侵袭和转移，补充和提高他的临床实践的重点是照顾 头颈癌患者。最终，他实验室的发现将被转化为临床应用。 该领域的目标是改善口腔癌患者的预后。 为了实现自己的职业目标，Neskey博士与Rosenzweig、沃森和加勒特博士合作- 梅尔的科学指导。每个委员会成员都有作为导师的既定记录， 独立调查员除了强大的指导委员会，耳鼻喉科部门 南卡罗来纳州医科大学的药理学和霍林斯癌症中心， 提供了受保护的时间、实验室空间和重要的启动包，以确保 研究环境。Neskey博士还建立了一个外部咨询委员会，由以下两人组成： 以前的导师，博士杰弗里迈尔斯和辛西娅莫顿谁提供额外的专业知识在p53领域 生物学和肿瘤遗传学分别将补充他的MUSC为基础的指导委员会。 在美国，头颈部癌症每年占60，000多例新癌症诊断，其中25-30%的人患有头颈部癌症。 患者最终死于他们的疾病，这表明需要继续进行研究， 确定导致这些患者不良结局的因素。一个有前途的研究领域是高风险的 肿瘤抑制基因TP 53的突变，与生存率降低相关， 大约50%的癌症。到目前为止，目前还不清楚这些突变如何使头部 颈部肿瘤细胞更具侵袭性。本提案所述的研究将直接涉及非政府组织的作用， 肌球蛋白IIA在突变型TP 53头颈癌抑癌能力中的作用 证明NMIIA功能障碍导致高风险突变型p53的特征，包括细胞增殖增加， 侵袭和肿瘤形成。最终，这项研究可能会导致针对这些疾病的精确治疗。 侵袭性肿瘤，并随后提高头颈癌患者的生存率。