耶鲁大学讲席教授樊荣讲述开启人体生命科学的未来

直播时间：2025年4月18日（周五）20:00-21:30

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北京时间2025年4月18日晚八点，iCANX Talks 第223期邀请到了耶鲁大学讲席教授樊荣作为主讲嘉宾，宾夕法尼亚大学助理教授Yanxiang Deng，中国科学院动物研究所Fangqing Zhao，新加波国立大学助理教授Jinmiao Chen担任研讨嘉宾，北京大学教授张海霞担任主持人。这将是一场汇聚顶尖学者的盛会，共同探讨前沿科技与学术挑战！更多精彩，敬请期待！

【嘉宾介绍】

樊荣‍

耶鲁大学

Ushering in a New Era of Human Biology

【Abstract】

The human body is an extraordinarily complex, dynamic, and heterogeneous multi-cellular system, which cannot be fully recapitulated by any model organism. As the saying goes, “mice get models, humans get disease.” Gaining a deep understanding of human molecular biology has long been a challenge, largely due to the limited ability to investigate biological mechanisms directly within human tissue specimens – especially those archived in clinical tissue banks worldwide. Over the past decade, spatial transcriptomics, enabled by imaging or sequencing-based approaches, has emerged as a powerful tool to map molecular and cellular landscapes and genome-wide gene expression profiles within intact tissues. However, these technologies have yet to integrate additional omics layers needed to reveal deeper biological mechanisms and to achieve full compatibility with clinically archived tissue samples. Our laboratory pioneered “spatial multi-omics” by achieving the first spatially resolved co-mapping of whole transcriptome and hundreds of proteins (Liu Y, et al., Cell, 2020), the first demonstration of “spatial epigenomics” sequencing (Deng Y, et al., Nature, 2022; Deng Y, et al., Science, 2022), as well as spatial co-profiling of epigenome and transcriptome on the same tissue sections (Zhang D, et al., Nature, 2023). However, formalin-fixed paraffin-embedded (FFPE) tissue blocks – the most abundant human biospecimens stored in clinical biobanks – have remained largely incompatible with spatial omics assays. This represents a critical unmet need and a major barrier to unlocking the full potential of human biology research and translational development. We recently developed Patho-DBiT – a first-of-its-kind platform for spatially resolved profiling of diverse RNA species – including microRNA, tRNA, snoRNA, lncRNA, region-specific RNA splicing isoforms, as well as genome-wide single-nucleotide RNA variants to decode cancer evolutionary dynamics in each patient’s tumor and reveal underlying epigenetic mechanisms – all from routinely archived clinical FFPE specimens (Bai Z, et al., Cell, 2024). Human clinical trials represent the most biologically relevant experiments for studying human biology. However, until recently, their utility in directly uncovering biological mechanisms with both depth and breadth from clinical biospecimens has been limited. This is now changing! Building upon efforts to develop virtual cell large-language models that capture the fundamental principles of molecular cell biology, spatial multi-omics technologies – including those pioneered in our laboratory – are poised to connect such models with spatial omics data. Together, they offer unprecedented power to decode the complexity of human biology and guide the design of personalized treatments, ushering in a new era of human biology research and precision health.

人体是一个极其复杂、动态且异质性的多细胞系统，任何模式生物都无法完全再现其全部特性。正如那句广为流传的话：“小鼠得模型，人类得疾病。”深入理解人类分子生物学一直是一个重大挑战，这在很大程度上是因为我们在直接研究人体组织样本中的生物机制方面能力有限 –尤其是那些储存在全球临床组织库中的病人组织样本。 在过去十年中，借助成像或测序技术的空间转录组学（spatial transcriptomics）成为了一个强有力的分析工具，用于在完整组织中绘制分子和细胞图谱以及全基因组范围内的基因表达图谱。然而，这些技术尚未很好的整合其他组学层面，从而无法深入揭示更复杂的生物机制，也难以与临床归档的组织样本（如 FFPE 样本）完全兼容。 我们实验室开创了“空间多组学”（spatial multi-omics）研究，率先实现了全转录组与数百种蛋白质的空间共定位图谱绘制（Liu Y et al，Cell, 2020），首次开展了“空间表观基因组学”测序（Deng Y et al，Nature, 2022；Science, 2022），以及在同一组织切片上实现了表观基因组与转录组的空间共分析（Zhang D et al，Nature, 2023）。然而，作为临床生物样本库中最丰富的人体样本类型，福尔马林固定石蜡包埋（FFPE）组织块仍与当前空间组学方法存在较大不兼容性，这构成了人体组织生物学研究和转化医学发展中的一个关键未满足需求和重大障碍。 为应对这一挑战，我们最近开发了Patho-DBiT – 首个实现多种RNA分子空间解析的平台。该平台可在常规归档的临床FFPE样本中，对包括microRNA、tRNA、snoRNA、lncRNA、区域特异性RNA剪接异构体以及全基因组单核苷酸RNA变异在内的多种RNA种类进行高分辨率空间分析，从而解析每位患者肿瘤的进化动态，并揭示其潜在的表观遗传机制（Bai Z et al，Cell, 2024）。临床试验是研究人体生物学最具生物学相关性的实验形式。直到最近，从临床样本中同时深入且广泛地揭示生物机制的能力依然受限。但这一状况正在发生改变！在构建虚拟细胞大语言模型以捕捉分子细胞生物学基本原理的努力基础上，空间多组学技术、包括我们实验室首创的方法，有望将此类模型与空间组学数据相连接。两者结合将前所未有地增强我们解析我们的能力来研究人体自身的复杂分子生物学，并推动个体化治疗设计的实现，开启人体组织生物学研究与精准健康的新时代。

【BIOGRAPHY】

Rong Fan, is the Harold Hodgkinson Professor of Biomedical Engineering and of Pathology at Yale University. He earned his Ph.D. in Chemistry from the University of California, Berkeley, and completed postdoctoral training at the California Institute of Technology before joining Yale University’s faculty in 2010. Dr. Fan’s research focuses on developing single-cell and spatial omics technologies to investigate functional cellular heterogeneity and intercellular signaling networks in human health and disease. He is a co-founder of IsoPlexis, Singleron Biotechnologies, and AtlasXomics and has served on the Scientific Advisory Board of Bio-Techne. His contributions have been recognized with numerous awards, including the National Cancer Institute’s Howard Temin Career Transition Award, the NSF CAREER Award, and the Packard Fellowship for Science and Engineering. He is an elected fellow of the American Institute for Medical and Biological Engineering (AIMBE), the Connecticut Academy of Science and Engineering (CASE), and the National Academy of Inventors (NAI).

樊荣（Rong Fan）博士是耶鲁大学生物医学工程系与病理学系的Harold Hodgkinson讲席教授。他在加州大学伯克利分校获得化学博士学位，并在加州理工学院完成博士后培训，于2010年加入耶鲁大学任教。 樊博士的研究主要致力于开发单细胞和空间组学技术，用以探索人类健康与疾病中的功能性细胞异质性及细胞间信号传导网络。他是IsoPlexis、Singleron Biotechnologies（欣悦生物）和AtlasXomics的联合创始人，并曾担任过Bio-Techne的科学顾问委员会成员。 他在科研方面的杰出贡献获得了众多奖项的认可，包括美国国家癌症研究所颁发的Howard Temin职业转型奖、美国国家科学基金会（NSF）青年学者奖（CAREER Award）以及帕卡德科学与工程奖学金（Packard Fellowship for Science and Engineering）。 他入选了美国医学与生物工程院（AIMBE）， 康涅狄格州科学院（CASE），以及美国国家发明家科学院（NAI）。

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