2024年5月14日，由基础医学院举办的清华大学生物医学前沿系列讲座（Frontier of Biomedical Seminar）2024年度第7期在医学科学楼B323顺利举行。本期讲座嘉宾吴船博士来自美国国家癌症研究所/癌症研究中心（NCI/CCR）实验免疫学分部，他此次的报告题目为：“Gut-liver axis calibrates intestinal stem cell fitness”。本期报告由胡小玉教授主持。
图1. 报告会现场
胡小玉老师首先对吴船博士此次来访基础医学院表示热烈的欢迎，她向在座师生详细介绍了吴船博士的研究经历和所取得的杰出成果。本期报告中，吴船教授幽默、风趣地与大家分享了他与实验团队在肠肝轴校准肠道干细胞适应度方面的多项研究进展。众所周知，肠道和肝脏通过胆道、门静脉和系统循环相互交流。然而，目前尚不清楚这种肠肝轴是如何调节肠道生理的。其团队通过肝切除术、转录组学和蛋白质组学分析，鉴定了色素上皮衍生因子（PEDF），一种肝衍生的可溶性Wnt抑制剂，通过抑制Wnt来抑制肠干细胞（ISC）的过度增殖，以维持肠道稳态Wnt/β-catenin信号通路。与此同时，研究发现肠道炎症产生的微生物危险信号可以被肝脏感知，从而通过过氧化物酶体增殖物激活受体-α（PPAR-α)抑制PEDF的产生，这种抑制释放ISC增殖，以加速肠道中的组织修复。此外，用非诺贝特（一种临床PPAR，用于降血脂的激动剂）治疗小鼠，由于PEDF活性而增强结肠炎易感性。因此确定PEDF在通过肠道和肝脏之间的相互作用来校准肠内稳态的ISC扩张中的独特作用。
图2.吴船博士做报告
本期讲座吸引了免疫学相关各实验室的老师和同学前来参加，会议期间座无虚席，报告结束进入到互动环节，在座老师和同学们积极热情踊跃提问，与吴船老师就学业目标、研究思路及实验方法等方面进行了热烈的交流与互动，吴船针对提出的每个问题都一一做出解答。
Biography
Dr. Wu completed his M.D. at Shanghai Jiaotong University, School of Medicine. He further undertook his doctoral research training at Muenster University, Germany, focusing on T cell migration during inflammation and autoimmunity. Then, he did his post-doctoral training at Brigham and Women’s Hospital, Harvard Medical School, where he studied transcriptional regulation for T cell differentiation. In 2016, Dr. Wu joined the faculty at Brigham and Women’s Hospital, Harvard Medical School as an Assistant Professor and then moved to NCI in 2017 as an Earl Stadtman Investigator, where he re-directed his research to understand intercellular regulation on mucosal barrier integrity.
His lab is utilizing interdisciplinary approaches to elucidate the crosstalk between the nervous system, microbial pathogens, and the immune system. Their findings on how intercellular communications modulate epithelial barrier function can potentially facilitate the discovery of novel therapeutic targets and approaches for Inflammatory Bowel Disease (IBD) and colon cancer. The observations and accomplishments so far are summarized in the following areas:
1. Reciprocal regulations between mucosal barrier and microbiota.
2. Neuro-immune crosstalk for the mucosal homeostasis in lungs and gastrointestinal tract.
3. Inter- and intra-epithelial regulation for intestinal barrier integrity.
Throughout his career, Dr. Wu has published many peer-reviewed manuscripts and review articles. His studies of cellular and molecular machineries of cell-cell interactions for regulating intestinal barrier function will have broad implications across the fields of immunology, physiology, and neuroendocrinology. His research will shed light on novel therapeutic targets to treat both intestinal inflammation and extraintestinal manifestations.
学生感想
吴船老师的talk一直是常听常新，每次都会有不一样的东西。这次关于gut-liver axis的工作依旧让人眼前一亮。本次讲座介绍的基于LPS和PEDF的肠肝互作调节机制和传统认知中高度依赖代谢产物（如短链脂肪酸、胆汁酸等）的互作路径很不一样，拓宽了我们对肠肝轴的理解。其中最令我惊叹的是研究和临床问题与实践的高度结合：这次介绍的研究很好地解释了Fenofibrate所伴随的肠炎副作用成因以及PEDF和炎症性肠病患者的疾病关联。这次的讲座又一次让我深刻感受到了基础医学研究的趣味、魅力和价值。
——基础医学院博士生留言
吴船教授此次的报告阐释了肠道和肝脏相互沟通的细胞和分子机制，他们的研究发现肝脏来源的PEDF可限制肠道干细胞增殖，而肝脏则可通过感知肠道来源的危险信号（LPS）减少PEDF产生从而形成闭环保护性的肠-肝轴。此外，他们还发现中和PEDF可大大缓解Fenofibrate (一种FDA批准的治疗低脂血症药物）所伴随的肠炎副作用，且在溃疡性结肠炎（UC）和克罗恩病（CD）病人急性期时，血液中PEDF和LPS的水平呈负相关，这一发现也提示PEDF可作为诊断 IBD 急性期标志物。
——基础医学院博士生留言
