Mentoring Patient Oriented Research in the Microbiome of Cancer and Stem Cell Transplant Patients

指导癌症和干细胞移植患者微生物组的以患者为导向的研究

• 批准号: 10593178
• 负责人: ANDREW Y KOH
• 金额: $ 11.69万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-14 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10593178
• 关键词: Antitumor Response; Award; Bacterial Infections; Basic Science; Biological; Cancer Patient; Centers for Disease Control and Prevention (U.S.); Child; Childhood; Clinic; Clinical; Clinical Investigator; Clinical Services; Communicable Diseases; Development; Diagnosis; Disease model; Etiology; Exposure to; Foundations; Funding; Future; Generations; Goals; Grant; Health; Hematology; Hematopoietic Stem Cell Transplantation; Immune checkpoint inhibitor; Immune response; Immune system; Immunocompromised Host; Immunology; Industry; Innate Immune Response; Institution; Intestinal Graft Versus Host Disease; Investigator-Initiated Research; K-Series Research Career Programs; Knowledge; Laboratories; Lead; Leadership; Malignant Neoplasms; Medical center; Mentors; Mentorship; Methods; Microbial Antibiotic Resistance; Microbiology; Mid-Career Clinical Scientist Award (K24); Mycoses; National Institute of Allergy and Infectious Disease; Oncologist; Oncology; Patient-Focused Outcomes; Patients; Phenotype; Physician Executives; Physicians; Play; Positioning Attribute; Privatization; Productivity; Research; Research Methodology; Research Personnel; Research Project Grants; Research Training; Resources; Role; Scientist; Shapes; Source; Specialist; Stem cell transplant; Structure; Supervision; Talents; Texas; Time; Training; Training Programs; Translations; Transplant Recipients; United States National Institutes of Health; Universities; Work; adaptive immune response; bacterial resistance; cancer cell; cancer immunotherapy; career; career development; checkpoint therapy; disease phenotype; experience; graft vs host disease; gut colonization; gut microbiome; gut microbiota; immunoregulation; improved; in vitro Model; insight; interest; microbial; microbiome; microbiome research; microbiome signature; mid-career faculty; next generation; novel; novel therapeutics; pathogenic bacteria; pathogenic fungus; patient oriented; patient oriented research; pediatric department; pre-clinical; prevent; programs; research and development; skills; translational approach; translational research program; translational scientist

Project Summary Dr. Andrew Y. Koh is an Associate Professor in the Department of Pediatrics (Division of Hematology/Oncology) and Microbiology at the University of Texas Southwestern Medical Center and Director of Pediatric Hematopoietic Stem Cell Transplantation at Children’s Medical Center Dallas. Clinically trained in both Infectious Diseases and Hematology/Oncology and scientifically trained in microbiology and immunology. Dr. Koh has established a successful and independent research program focused on understanding how the gut microbiome modulates host immune responses in cancer and stem cell transplant (SCT) patients. His experiences as an active clinical oncologist and infectious diseases specialist, a basic/translational researcher, and mentor have positioned him to be an ideal candidate for the K24 Mentoring Career Development Award. For this project, he is particularly interested in using “reverse translational” approaches to identify unique gut microbiome signatures associated with a particular disease phenotype in patients and then confirming causality in the laboratory using preclinical and in vitro models. Hence, his research program is well-poised to further dissect and elucidate the mechanisms by which specific gut microbiota modulate disease phenotypes in cancer and SCT patients with the ultimate goal of devising novel therapies to modulate the gut microbiota and promote patient health. This work has been supported by funding from the NIH/NIAID (K08 and R01), the Centers for Disease Control and Prevention, private foundations, and industry. He has also developed a significant professional interest in mentoring trainees in translational microbiome research and career development. The K24 award will support Dr. Koh’s scientific career activities by allowing him to engage in professional development via coursework/training and execution of novel projects that will enhance his research program and support future independent funding. In addition to supporting scientific career activities, the K24 award will directly allow Dr. Koh to pursue mentorship/leadership training and enhance his ability to more deeply engage with specific mentees pursuing K and R01 awards and more broadly engage with all mentees in patient-oriented microbiome research. The overall scientific aims of this proposal are 1) To mentor trainees to become patient-oriented research investigators; 2) To continue and enhance my career development as a leader in translational patient- oriented research; and 3) To conduct independent translational microbiome research to improve the health of cancer and SCT patients with a focus on the following specific research projects: a) Mechanisms of gut colonization resistance to bacterial and fungal pathogens, with a translational focus on devising novel methods to precisely edit the microbiome and prevent invasive bacterial/fungal infections; b) Gut microbiota-dependent modulation of graft-versus-host disease; c) Mechanisms by which gut microbiota augment host anti-tumor response in the context of cancer immunotherapy; and d) Host and microbial determinants of microbial antibiotic resistance.

项目概要 Andrew Y. Koh 博士是儿科（血液学/肿瘤学部）的副教授 德克萨斯大学西南医学中心微生物学和儿科主任 达拉斯儿童医疗中心的造血干细胞移植。接受过传染病方面的临床培训 疾病和血液学/肿瘤学，并接受过微生物学和免疫学方面的科学培训。许医生有 建立了一个成功且独立的研究计划，专注于了解肠道微生物组如何 调节癌症和干细胞移植 (SCT) 患者的宿主免疫反应。他作为一名 活跃的临床肿瘤学家和传染病专家、基础/转化研究员和导师 使他成为 K24 辅导职业发展奖的理想候选人。为了这个项目，他 对使用“反向翻译”方法来识别独特的肠道微生物组特征特别感兴趣 与患者的特定疾病表型相关，然后在实验室中使用以下方法确认因果关系 临床前和体外模型。因此，他的研究计划已准备好进一步剖析和阐明 特定肠道微生物群调节癌症和 SCT 患者疾病表型的机制 最终目标是设计新疗法来调节肠道微生物群并促进患者健康。这部作品 得到了 NIH/NIAID（K08 和 R01）、疾病控制中心和 预防、私人基金会和工业。他还对以下领域产生了浓厚的专业兴趣： 指导学员进行转化微生物组研究和职业发展。 K24奖将支持 Koh 博士的科学职业活动使他能够通过以下途径从事专业发展 课程作业/培训和新项目的执行将增强他的研究计划并支持未来 独立资助。除了支持科学事业活动外，K24 奖还将直接授予 Dr. Koh 寻求指导/领导力培训，并提高他更深入地参与特定领域的能力 追求 K 和 R01 奖的受训者，并更广泛地与所有受训者接触以患者为导向的微生物组 研究。该提案的总体科学目标是 1) 指导受训者以患者为中心 研究人员； 2) 继续并加强我作为转化患者领导者的职业发展- 定向研究； 3) 进行独立的转化微生物组研究，以改善人们的健康 癌症和 SCT 患者，重点关注以下具体研究项目：a) 肠道机制 对细菌和真菌病原体的定植抗性，重点是设计新方法 精确编辑微生物组并预防侵入性细菌/真菌感染； b) 肠道微生物群依赖性 调节移植物抗宿主病； c) 肠道微生物群增强宿主抗肿瘤的机制 癌症免疫治疗背景下的反应； d) 微生物抗生素的宿主和微生物决定因素 反抗。