Protein Phosphorylation Networks in Health and Disease

健康和疾病中的蛋白质磷酸化网络

• 批准号: 10682983
• 负责人: Kristen M Naegle
• 金额: $ 0.48万
• 依托单位: FEDERATION OF AMER SOC FOR EXPER BIOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10682983
• 关键词: Academia; Achievement; Address; Area; Award; Binding; Biochemical; Biology; Cells; Cellular biology; Characteristics; Clinic; Clinical Sciences; Collaborations; Compensation; Development; Developmental Process; Diabetes Mellitus; Discipline; Disease; Drug Industry; Drug Targeting; Educational workshop; Epidermal Growth Factor Receptor; Exposure to; FDA approved; Financial Support; Funding; Future; Genetic; Goals; Health; Human; Immersion; Industry; Investments; Knowledge; Learning; Link; Malignant - descriptor; Malignant Neoplasms; Mediating; Metabolic Diseases; Methods; Molecular; Mutation; Nerve Degeneration; Oncology; Outcome; Participant; Pathologic; Patients; Pharmaceutical Preparations; Phosphorylation; Phosphotransferases; Physiological; Progression-Free Survivals; Protein Kinase; Protein Kinase Protein Phosphorylation; Regulation; Request for Applications; Research; Resistance; Role; Scientist; Senior Scientist; Series; Signal Transduction; Specificity; Structure; Survival Rate; System; Techniques; Technology; Therapeutic; Toxic effect; Translational Research; Travel; Treatment Efficacy; combat; combinatorial; developmental disease; drug discovery; human disease; improved; innovation; insulin signaling; interest; mathematical methods; mutant; neurotransmission; next generation; novel strategies; novel therapeutics; posters; prevent; programs; protein function; resistance mechanism; response; skeletal disorder; small molecule inhibitor; success; symposium; targeted treatment; therapeutic target; translational scientist; virtual

Summary Kinases regulate normal physiological response to environmental perturbations. When dysregulated, either through aberrant expression or mutation, protein kinases have been implicated in a host of diseases, from developmental disorders to cancer. Accordingly, many of the successful targeted therapeutics for cancer and developmental diseases have been generated against aberrantly activated kinases. Unfortunately, the therapeutic efficacy of most of these agents has been largely disappointing due to the emergence of resistance caused in part by rewiring of the signaling networks and by mutations that interfere with drug binding. In many cases, mutant kinases cannot be efficiently inhibited due to our incomplete understanding of the effect that disease mutations exert on kinase activation state, downstream network compensation, and anticipated response to a drug. Understanding the normal physiological role of protein kinases and their phosphorylation networks 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. There are three specific objectives of the FASEB 2023 Protein Phosphorylation Networks in Health and Disease Conference. The first objective is to describe the state of the art in kinase structure, function, localization, regulation, interactions, and targeting in both normal and pathological cell states. 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, 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 and to enhance interactions between research approaches, from biochemical-, structural-, systems-level, and computational fields related to phosphorylation. To this end, we have specifically invited speakers representing each of these topics, and are planning workshops on new techniques in the field. The third objective is to invest intellectually and financially in the future by supporting promising young trainees, with an eye towards increasing diversity in the field. 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 kinase signaling, and exploration of new state of the art approaches for identifying and developing therapeutic targets and strategies to combat cancer, developmental deficiencies, and other diseases.

总结 激酶调节对环境扰动的正常生理反应。当失调时， 通过异常表达或突变，蛋白激酶与许多疾病有关， 发展障碍到癌症。因此，许多成功的癌症靶向治疗方法， 针对异常激活的激酶已经产生了发育疾病。可惜 由于耐药性的出现 部分原因是信号网络的重新布线和干扰药物结合的突变。在许多 在某些情况下，突变激酶不能被有效地抑制，因为我们对突变激酶的作用不完全了解， 疾病突变对激酶激活状态、下游网络补偿和预期的 对药物的反应了解蛋白激酶及其磷酸化的正常生理作用 网络将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。那里 FASEB 2023蛋白质磷酸化网络在健康和疾病中的三个具体目标 会议第一个目的是描述激酶结构、功能、定位、 在正常和病理细胞状态中的调节、相互作用和靶向。为了实现这一目标，我们 我已经计划了一系列的主题演讲和全体会议发言，来自该领域的许多领先专家，多个 从海报摘要、海报会议、几个重点研讨会和非正式会议中选出的简短演讲 讨论。由于这一领域的挑战十分艰巨，需要各方共同努力加以解决， 第二个目标是加强学术界、工业界和临床科学之间的互动， 研究方法之间的相互作用，从生物化学，结构，系统水平，和计算 与磷酸化有关的领域。为此，我们特别邀请了代表这些国家的发言者， 主题，并计划在该领域的新技术讲习班。第三个目标是智力投资 通过支持有前途的年轻受训人员，在未来的财政和经济上，着眼于增加多样化， 外地目标是通过提供知识，鼓励学员取得成功并留在该领域 通过与资深科学家的讨论、海报会议、发言机会、 通过表彰他们的成就，并提供具有竞争力的旅行奖励的财政支持。预期 结果是增加了合作，留住了该领域的年轻科学家，确定了新的 与激酶信号相关的发育过程和疾病，以及探索最新技术水平 用于识别和开发治疗靶点和策略的方法，以对抗癌症、发展 缺陷和其他疾病。