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

项目摘要 博士安德鲁·Y Koh是儿科（血液学/肿瘤学分部）的副教授 德克萨斯大学西南医学中心的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。接受过传染病和 疾病和血液学/肿瘤学，并在微生物学和免疫学方面受过科学培训。许医生 建立了一个成功的独立研究项目，专注于了解肠道微生物组如何 调节癌症和干细胞移植（SCT）患者的宿主免疫应答。他作为一名 活跃的临床肿瘤学家和传染病专家，基础/转化研究人员和导师， 使他成为K24职业发展指导奖的理想候选人。对于这个项目，他 特别感兴趣的是使用“反向翻译”方法来识别独特的肠道微生物组特征 与患者的特定疾病表型相关，然后在实验室使用 临床前和体外模型。因此，他的研究计划准备进一步剖析和阐明 特定肠道微生物群调节癌症和SCT患者疾病表型的机制 最终目标是设计新的疗法来调节肠道微生物群并促进患者健康。这项工作 由NIH/NIAID（K 08和R 01）、疾病控制中心和 预防、私人基金会和工业。他还对以下方面产生了浓厚的专业兴趣： 指导转化微生物组研究和职业发展的学员。K24奖将支持 博士Koh的科学职业活动，使他能够通过 课程/培训和新项目的执行，将加强他的研究计划，并支持未来 独立融资。除了支持科学事业活动，K24奖将直接允许博士。 Koh将继续接受导师/领导力培训，并提高他更深入地参与具体工作的能力。 寻求K和R 01奖项的学员，并在以患者为导向的微生物组中更广泛地与所有学员接触 research.该建议的总体科学目标是：1）指导学员以患者为导向 研究调查员; 2）继续并加强我作为翻译患者领导者的职业发展- 3）进行独立的转化微生物组研究，以改善 癌症和SCT患者，重点关注以下具体研究项目： 对细菌和真菌病原体的定殖抗性，翻译重点是设计新方法 精确编辑微生物组并防止侵入性细菌/真菌感染; B）肠道微生物依赖性 c）肠道微生物群增强宿主抗肿瘤能力的机制 d）微生物抗生素的宿主和微生物决定因素 阻力

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.