FASEB SRC on Protein Kinases, Cellular Plasticity and Signal Rewiring

FASEB SRC 关于蛋白激酶、细胞可塑性和信号重新布线

• 批准号: 8782243
• 负责人: Forest M White
• 金额: $ 0.45万
• 依托单位: FEDERATION OF AMER SOC FOR EXPER BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-08 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8782243
• 关键词: Academia; Achievement; Address; Adverse effects; Affect; Area; Award; Biological Products; Biology; Biotechnology; Cancer Biology; Cells; Cellular Stress; Characteristics; Clinic; Clinical Oncology; Clinical Sciences; Collaborations; Combined Modality Therapy; Development; Developmental Process; Discipline; Disease; Drug Industry; Drug Targeting; Educational workshop; Epidermal Growth Factor Receptor; Financial Support; Funding; Future; Goals; Immersion Investigative Technique; Industry; Knowledge; Lead; Learning; Link; Lipids; Malignant - descriptor; Malignant Neoplasms; Mediating; Medicine; Metabolic Diseases; Molecular; Mutation; Oncogenes; Oncogenic; Outcome; Participant; Patients; Pharmacologic Substance; Phosphorylation; Phosphotransferases; Physiological; Progression-Free Survivals; Protein Kinase; Protein Kinase Protein Phosphorylation; Protein Tyrosine Kinase; Proteins; Regulation; Request for Applications; Research; Research Personnel; Resistance; Role; Scientist; Senior Scientist; Series; Signal Transduction; Structure; Survival Rate; Technology; Therapeutic; Therapeutic Intervention; Translational Research; Translations; Travel; Treatment Efficacy; Tumor Tissue; abstracting; base; combat; combinatorial; improved; interest; meetings; new technology; next generation; novel therapeutics; oncology; posters; prevent; programs; public health relevance; resistance mechanism; response; small molecule; success; symposium; therapeutic target

DESCRIPTION (provided by applicant): Kinases regulate normal physiological response to environmental perturbations. When dysregulated, either through aberrant expression or mutation, protein and lipid kinases have been implicated in a host of diseases, from metabolic disorders to cancer. Tyrosine kinases were among the earliest oncogenes, and have emerged as primary drivers of multiple cancer subtypes. Accordingly, many of the targeted therapeutics for cancer, including small molecule and biological agents, have been generated against oncogenic kinases. Unfortunately, the therapeutic efficacy of these molecularly targeted agents has been largely disappointing due to the emergence of therapeutic resistance, much of which is caused by rewiring of the signaling network. Understanding the normal physiological role of protein kinases, as well as their altered substrates and signaling networks in disease states, will significantly improve our ability to selectively target disease- associated kinases and will enable the development of next-generation targeted combinatorial therapeutics with greatly increased efficacy. Some of the main challenges in the field are to improve our knowledge of how kinases regulate cell states and control cellular plasticity, and how kinase signaling networks respond to cellular stress associated with therapeutic treatment. There are three specific objectives of the FASEB 2014 Protein Kinases, Cellular Plasticity and Signal Rewiring Conference. The first objective is to describe the state of the art in kinase structure, function, localization, regulatin, interactions, and targeting in both normal and pathological cell states, as this information will provide critical clues as to how to differentially affect diseased states and thereby increase the therapeutic window, as defined by the difference between targeting the disease and developing toxic side effects. To accomplish this goal we have planned a series of keynote and plenary speakers from many of the leading experts in the field, multiple short talks selected from the poster abstracts, poster sessions, question and answer sessions, several focused workshops, and informal discussions. Since the challenges in this field are daunting and will require collaborative efforts to solve them, the second goal is to enhance interactions between academia, industry, and clinical science. To this end, we have specifically invited speakers representing each of these topics, and are planning a workshop to discuss signaling rewiring and cellular plasticity in therapeutic resistance mechanisms. The third objective is to invest intellectually and financially in the future by supporting promising young trainees. The goal is to encourage trainees to be successful and stay in the field by providing intellectual support through discussions with senior scientists, poster sessions, opportunities to speak, awards that recognize their achievements, and by providing financial support with competitive travel awards. The expected outcomes are increased collaborations, retention of young scientists in the field, identification of new developmental processes and diseases linked to tyrosine kinase signaling, and exploration of new avenues and approaches for identifying and developing therapeutic targets and strategies to combat cancer, developmental deficiencies, and other diseases.

描述（由申请人提供）：激酶调节对环境扰动的正常生理反应。当通过异常表达或突变而失调时，蛋白质和脂质激酶已经涉及从代谢紊乱到癌症的许多疾病。酪氨酸激酶是最早的致癌基因之一，并且已经成为多种癌症亚型的主要驱动因素。因此，许多针对癌症的靶向治疗剂，包括小分子和生物制剂，已经针对致癌激酶产生。不幸的是，这些分子靶向药物的治疗效果在很大程度上令人失望，这是由于出现了治疗耐药性，其中大部分是由信号网络的重新布线引起的。了解蛋白激酶的正常生理作用，以及它们在疾病状态下改变的底物和信号网络， 显著提高我们选择性靶向疾病相关激酶的能力， 下一代靶向组合疗法的发展，大大提高了疗效。该领域的一些主要挑战是提高我们对激酶如何调节细胞状态和控制细胞可塑性的认识，以及激酶信号网络如何响应与治疗相关的细胞应激。FASEB 2014蛋白激酶、细胞可塑性和信号重连会议有三个具体目标。第一个目标是描述激酶结构、功能、定位、调节、相互作用和在正常和病理细胞状态下的靶向方面的最新技术水平，因为这些信息将提供关于如何差异性地影响疾病状态并从而增加治疗窗口的关键线索，如靶向疾病和产生毒副作用之间的差异所定义的。为了实现这一目标，我们计划了一系列来自该领域许多领先专家的主题演讲和全体演讲，从海报摘要中选择的多个简短演讲，海报会议，问答会议，几个重点研讨会和非正式讨论。由于这一领域的挑战是艰巨的，需要共同努力来解决这些问题，第二个目标是加强学术界，工业界和临床科学之间的互动。为此，我们特别邀请了代表这些主题的演讲者，并计划举办一个研讨会，讨论治疗抗性机制中的信号重连和细胞可塑性。第三个目标是通过支持有前途的年轻受训者，对未来进行智力和财政投资。目标是 鼓励受训人员取得成功并留在实地，为此提供智力支持，包括与资深科学家讨论、张贴海报、提供发言机会、颁发表彰其成就的奖项，以及提供具有竞争力的旅行奖等财政支持。预期的成果是增加合作，留住该领域的年轻科学家，识别与酪氨酸激酶信号相关的新的发育过程和疾病，以及探索新的途径和方法，用于识别和开发治疗靶点和策略，以对抗癌症，发育缺陷和其他疾病。