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

项目摘要 许志勇医生是儿科(血液/肿瘤科)副教授。 和微生物学在德克萨斯大学西南医学中心和儿科主任 达拉斯儿童医学中心的造血干细胞移植。在两种传染病方面接受过临床培训 疾病和血液学/肿瘤学，并在微生物学和免疫学方面接受过科学培训。Koh博士已经 建立了一个成功的独立研究项目，专注于了解肠道微生物群是如何 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 积极的临床肿瘤学家和传染病专家，基础/翻译研究人员和导师 将他定位为K24导师职业发展奖的理想候选人。对于这个项目，他 对使用“反向翻译”方法来识别独特的肠道微生物群特征特别感兴趣 与患者的特定疾病表型相关联，然后在实验室中使用 临床前和体外模型。因此，他的研究计划已做好准备，将进一步剖析和阐明 特定肠道微生物区系调节癌症和SCT患者疾病表型的机制 最终目标是设计新的治疗方法来调节肠道微生物区系，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 指导受训人员进行微生物翻译研究和职业发展。K24奖将支持 Koh博士的科学职业活动，允许他通过 课程/培训和执行新颖的项目，以加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奖还将直接允许Dr。 Koh继续进行导师/领导力培训，并增强他更深入地参与特定项目的能力 学员追求K和R01奖项，并更广泛地与所有学员接触以患者为导向的微生物群 研究。这项建议的总体科学目标是：1)指导受训人员变得以病人为本 研究人员；2)继续并加强我作为翻译患者领导者的职业发展- 以研究为导向；以及3)进行独立的翻译微生物组研究，以改善 癌症和SCT患者，重点关注以下具体研究项目：a)肠道机制 对细菌和真菌病原体的定植抗性，翻译重点是设计新的方法 精确编辑微生物组，防止侵袭性细菌/真菌感染；b)依赖肠道微生物区系 移植物抗宿主病的调控；c)肠道微生物区系增强宿主抗肿瘤的机制 在癌症免疫治疗方面的反应；和d)微生物抗生素的宿主和微生物决定因素 抵抗。

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.