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

项目摘要/摘要 Neskey博士的短期目标是在方法学、概念性和 以实验室为基础的科学研究的理论方法，这将有助于他确定 非肌肉肌球蛋白IIA(NMIIA)在头颈癌中调节抑癌基因P53中的作用。K08 获奖将使他作为一名科学家进一步成熟，并发展技能、工具、知识和专业知识 在科学领域出类拔萃。预计在K08资助期内，他将处于有利地位 提交研究项目拨款申请(R01)，代表其研究的自然进展 此K08拨款提案中的活动。内斯基博士的长期职业目标是带头 作为一名外科医生兼科学家，独立资助的全面研究计划探索了 肿瘤细胞侵袭和转移，补充和加强了他的临床实践，专注于治疗 头颈部癌症患者。最终，来自他的实验室的发现将转化为临床 其目标是改善口腔癌患者的治疗结果。 为了实现他的职业目标，内斯基博士与罗森茨韦格、沃森和加勒特博士合作- 梅耶尔科学导师奖。每个委员会成员都有既定的导师记录和 独立调查员。除了强大的指导委员会，耳鼻咽喉科 南卡罗来纳医科大学和霍林斯癌症中心的药理学 提供受保护的时间、实验室空间和重要的启动包，以确保可靠和高效的 研究环境。Neskey博士还建立了一个外部咨询委员会，由两名成员组成 之前的导师，Jeffrey Myers博士和Cynthia Morton博士，他们在p53领域提供了额外的专业知识 生物学和肿瘤遗传学，这将补充他在MUSC的指导委员会。 在美国，头颈癌每年新诊断的癌症病例超过6万例，其中25%-30% 患者最终死于他们的疾病，这表明有必要继续研究 找出导致这些患者预后不佳的因素。高风险是一个很有前途的研究领域 肿瘤抑制基因TP53的突变与存活率降低有关 在这些癌症中，大约有50%。到目前为止，人们还不清楚这些突变是如何使Head 而颈部肿瘤细胞侵袭性更强。本提案中描述的研究将直接涉及非 肌肉肌球蛋白IIA在突变型TP53对头颈部肿瘤抑制作用中的作用 证明NMIIA功能障碍导致高危突变型P53的特征，包括细胞增加 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，进而提高头颈癌患者的存活率。

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.