BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10091811
• 负责人: William Maurice Shafer
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-10-01 至 2027-09-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10091811
• 关键词: Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Area; Award; Azithromycin; Bacteria; Bacterial Antibiotic Resistance; Bacterial Infections; Basic Science; Biological; Biological Models; Cefixime; Ceftriaxone; Cephalosporins; Communicable Diseases; Communities; Country; Coupled; Development; Disease; Disease Resistance; Education; Educational process of instructing; Faculty; Female; Funding; Funding Agency; Generations; Goals; Gonorrhea; Gynecologic; Health; Homeostasis; Host Defense; Human; Incidence; Infection; Infectious Agent; International; Journals; Knowledge; Laboratories; Leadership; Light; Link; Mediator of activation protein; Medical Research; Medicine; Membrane; Mentors; Military Personnel; Molecular; Mucous Membrane; Neisseria gonorrhoeae; Pathogenesis; Peer Review; Permeability; Pharmaceutical Preparations; Population; Postdoctoral Fellow; Public Health; Reporting; Research; Resistance; Resistance development; Resources; Science; Scientist; Sepsis; Services; Sexual Transmission; Sexually Transmitted Diseases; Societies; Study Section; Surface; System; Transcriptional Regulation; Translational Research; United States; United States National Institutes of Health; Universities; Vaccines; Veterans; Virulence Factors; Work; antimicrobial; base; career; career development; clinical practice; combat; doctoral student; efflux pump; human pathogen; improved; male; medical schools; meetings; microbial; pathogen; pathogenic bacteria; pre-doctoral; programs; resistance factors; resistant strain; student mentoring; therapeutic vaccine; translational study; treatment strategy; vaccine development

Project Summary In this competitive renewal of my Senior Research Career Scientist (SRCS) award I will continue my research, service, and teaching/mentoring efforts that have been the areas of concentration during past funding periods. My research program focuses on antibiotic resistance as it is now recognized that the ability of bacterial pathogens to evade the action of antibiotics is now one of the most important threats to worldwide public health. My research program since entering the VA Medical Research service in 1987 has been to understand the molecular basis by which bacteria develop resistance to antimicrobials with the ultimate goal of advancing basic science knowledge to improving human health. As a model system, the laboratory has largely used the human sexually transmitted pathogen Neisseria gonorrhoeae since this pathogen has historically developed resistance to every antibiotic that has been brought into clinical practice and has a remarkable ability to avoid the action of multiple host defense systems. Our research focus is of importance to both the veteran/active military and civilian populations in the United States given that over 550,000 cases of gonorrhea are reported yearly with over 50% of N. gonorrhoeae isolates resistant to one or more antibiotics. Moreover, the worldwide estimate of cases approaches 100 million with reported instances of strains resistant to front-line antibiotics (azithromycin and/or ceftriaxone). A major accomplishment of my laboratory has been the finding that mechanisms of antibiotic resistance including multidrug efflux pumps, drug permeability changes due to alterations in outer membrane structure and inner membrane homeostasis can be linked to the ability of gonococci to evade mediators of host defense and survive during experimental infections. Thus, we advanced the concept that antibiotic resistance and bacterial pathogenesis are not necessarily separate entities and should be studied together. Importantly, our basic research efforts have now reached a point where translational-driven efforts can facilitate vaccine development and new antibiotic discovery. In addition to these research efforts, I have participated in and provided leadership for multiple local, national and international endeavors to combat antibiotic resistance. These efforts include extensive peer-review service for journals and study sections, membership on national and international advisory boards for agencies advancing new antibiotic development, teaching/mentoring programs through directing an NIH-funded T32 program for pre-doctoral students, developing and directing graduate level courses, and mentoring junior faculty at the Atlanta VA and Emory University School of Medicine. These extensive efforts coupled with my ongoing productive research program will be the focus of my SRCS-supported work during the next funding period.

项目摘要 在我的高级研究职业科学家（SRCS）奖的竞争更新中，我将继续我的研究， 在过去的资金期间，服务，教学/指导工作一直是集中注意力的领域。 我的研究计划侧重于抗生素耐药性，因为现在已经认识到细菌的能力 逃避抗生素作用的病原体现在是对全球公共卫生的最重要威胁之一。 自1987年进入VA医学研究服务以来，我的研究计划一直是为了了解 细菌通过对抗菌剂产生抗性的分子基础，其最终目标是促进碱性 科学知识以改善人类健康。作为模型系统，实验室在很大程度上使用了人类 性传播病原体淋病奈瑟氏病，因为这种病原体在历史上发展了抗性 对于每种被带入临床实践的抗生素，并且具有出色的能力避免行动 多个主机防御系统。我们的研究重点对于老兵/活跃军队和 鉴于每年有超过550,000例淋病案件，美国的平民人口 超过50％的淋病猪笼草分离株对一种或多种抗生素具有抗性。此外，全球估计 病例接近1亿个抗菌株的菌株（阿奇霉素）的菌株实例 和/或头孢曲松）。我实验室的重大成就是发现 抗生素耐药性，包括多种液外排泵，由于改变而改变的药物渗透性变化 外膜结构和内膜内稳态可以与淋球菌的能力联系在一起 在实验感染期间，逃避宿主防御和生存的探测者。因此，我们推进了 抗生素耐药性和细菌发病机理不一定是分开的概念，应 一起研究。重要的是，我们的基础研究工作已经达到了以翻译为导向的地步 努力可以促进疫苗开发和新的抗生素发现。除了这些研究工作，我 已经参与并为战斗的多个地方，国家和国际努力提供了领导 抗生素抗性。这些努力包括针对期刊和研究部分的广泛的同行评审服务， 国际和国际咨询委员会的成员资格推进新的抗生素开发， 通过为博士前学生指挥NIH资助的T32计划，教学/指导课程， 开发和指导研究生级课程，并在亚特兰大弗吉尼亚州和埃默里指导初级教师 大学医学院。这些广泛的努力以及我正在进行的生产研究计划 在下一个资金期间，将是我SRCS支持的工作的重点。