BLRD Research Career Scientist Award Application

癌症是退伍军人的第二大死因，退伍军人健康管理局 据估计，退伍军人管理局系统内有17万名癌症患者。此外，大约有5万人 每年都会诊断出新的癌症病例。随着退伍军人人口的老龄化，这一数字预计将达到 增加，导致伴随而来的对医疗资源的阻碍。肺癌，这是最主要的 工业化国家男性和女性的死因(估计占所有癌症死亡人数的28% (美国)，也是退伍军人中癌症死亡的主要原因。事实上，许多退伍军人继续 在服兵役期间染上烟草瘾，尽管目前不鼓励烟草滥用 军队。因此，有很大比例的高风险现任和前任吸烟者在 VA医疗保健系统将受益于治疗分子靶向治疗的进展 肺癌。此外，肺癌也与公认的致癌物质有关，橙剂、石棉、 而暴露在这些物质中的电离辐射通常是与服务相关的疾病。 为了解决这个问题，Chalfant实验室的研究重点是非小细胞肺癌 代表大多数肺癌的非小细胞肺癌(NSCLC)预后较差，中位生存期较低 超过12个月，累计五年存活率约为15%。Chalfant的研究 实验室是专门为开发这种致命疾病的新治疗方法而量身定做的 因此，这些问题与退伍军人事务部的病人护理任务直接相关。 事实上，调查肺癌治疗发展新策略的生物医学研究已经 退伍军人有巨大的潜在利益，他们中的许多人不再吸烟，但仍处于非小细胞肺癌的高危状态。 Chalfant实验室专注于关于细胞的两个主要但不同的基础科学领域 生物学、微生物学和分子生物学。具体地说，Chalfant实验室研究细胞的机制 与生物活性脂质和RNA剪接相关的信号转导，重点介绍这两种基本科学机制 以及在许多情况下的临床翻译。关于RNA剪接的研究，Chalfant实验室已经 确定了介导非小细胞肺癌细胞肿瘤维持的关键RNA剪接事件和信号机制。 申请者进一步将这些发现与与细胞存活有关的新的脂质信号事件合并。 申请者查尔凡特博士在与&gt；100同行评议的出版物上卓有成效，他已经 17年来一直是退伍军人制度的杰出成员。他的研究工作得到了几个美国国立卫生研究院/退伍军人管理局的支持 资助的项目，目前，他有一个VA功绩审查奖和三个NIH资助的项目(2-R01和1- U01)。他已经培训了40多名不同级别的实习生，其中一些人目前是 有资助研究项目的各种机构。申请者是年轻调查人员的无私导师 允许他们在许多出版物上担任联合通讯作者，以改善他们的职业生涯。 申请人仍然是其科学领域的领导者，这一点从几个编辑委员会的任命中可见一斑。 和国家委员会，其中包括：《血脂研究杂志》的编辑委员会。分子癌 研究和生物化学杂志，癌症和分子的正式成员 美国国立卫生研究院病理生物学研究部，肿瘤学A研究的正式成员 退伍军人管理局的部门。这些研究领域也导致了2011年的交流 ASBMB Avanti血脂研究初级研究员奖颁发给Chalfant博士。申请人还拥有广泛的 在资助的计划项目和科学出版物中与众多研究人员合作。 总之，申请者的科学贡献对退伍军人管理局的任务至关重要。他已经做出了 在非小细胞肺癌、RNA剪接、脂质组学和脂质信号领域的突破性发现，还 为科学界和退伍军人制度提供了大量资源。

Cancer is the second leading cause of death among veterans, and the Veterans Health Administration estimates that there exist >170,000 cancer patients within in the VA system. Moreover, approximately 50,000 new cases of cancer are diagnosed each year. With the aging of the veteran population, this number is expected to increase causing a concomitant encumbering of healthcare resources. Lung cancer, which is the leading cause of death in both men and women in industrialized countries (an estimated 28% of all cancer deaths in the USA), is also the leading cause of cancer death in the veteran population. Indeed, many veterans continue to acquire tobacco addiction during their military service even though tobacco abuse is currently discouraged by the military. Hence, there exists a very large percentage of high-risk current and former smokers cared for in the VA health care system that would benefit from advances in therapeutic molecular targeting in the treatment of lung cancer. Also, lung cancer is also linked to the well-established lung carcinogens, Agent Orange, Asbestos, and Ionizing Radiation, which exposure to these agents are often are service-connected disorders. To address this issue, the research of the Chalfant Laboratory focuses on non-small cell lung cancer (NSCLC), which represents the majority of lung cancers, carries a poor prognosis with a median survival of less than 12 months, and has a cumulative five-year survival rate of approximately 15%. The research of the Chalfant Laboratory is tailored to identify new cellular targets for the development of new treatments for this deadly disease, which are thus, directly relevant to the patient care mission of the Department of Veterans Affairs. Indeed, biomedical research investigating new strategies for the development of lung cancer therapeutics has tremendous potential benefit to veterans, many of whom no longer smoke, yet remain at high risk for NSCLC. The Chalfant Laboratory focuses on two major, but diverse areas of basic science in regard to Cell Biology, Microbiology, and Molecular Biology. Specifically, the Chalfant Laboratory studies mechanisms of cell signaling associated with both bioactive lipids and RNA splicing with a focus on both basic science mechanisms as well as in many cases clinical translation. In regard to RNA splicing research, the Chalfant Laboratory has identified key RNA splicing events and signaling mechanisms mediating the tumor maintenance of NSCLC cells. The applicant is further merging these finding with novel lipid signaling events linked to cell survival. The applicant, Dr. Chalfant, has been very productive with >100 peer-reviewed publications, and he has been a distinguished member of the VA system for 17 years. His research work is supported by several NIH/VA funded projects and currently, he has one VA Merit Review award and three NIH funded projects (2-R01 and 1- U01). He has trained more than 40 trainees at very levels with a number of them currently faculty members at various institutions with funded research programs. The applicant is an unselfish mentor of young investigators allowing them to act as co-corresponding authors on numerous publications for the betterment of their careers. The applicant continues to be a leader in his scientific field as shown by appointments to several Editorial Boards and National Committees, which include: the editorial boards of the Journal of Lipid Research. Molecular Cancer Research, and the Journal of Biological Chemistry, formal membership on the Cancer and Molecular Pathobiology Study Section of the National Institutes of Health, and formal membership on the Oncology A Study Section of the Veterans’ Administration. These areas of research also led to the communication of the 2011 ASBMB Avanti Junior Investigator Award for Lipid Research to Dr. Chalfant. The applicant has also extensively collaborated with numerous investigators in funded program projects and scientific publications. In summary, the applicant’s scientific contributions are vitally important to the VA mission. He has made ground breaking discoveries in the field of NSCLC, RNA Splicing, Lipidomics, and Lipid Signaling and has also provided significant resources to the scientific community and the VA system.