申请者主要从事中药药效物质研究。近5年来，应对慢性肾病高发但临床上缺乏药物的严峻形势，从中医治则治法出发，针对性选择分别具有活血、补虚或通络功效的特色树脂类（干漆等）、菌类（灵芝等）和虫类（九香虫等）中药，在中医药理论与仿生学理念指导下，首次围绕慢性肾病开展系统研究。采用多种色谱与光谱手段高效组合的去重复化方法，从中发现了203个靶向TGF-β/Smads或Wnt/β-catenin等信号通路的肾保护活性成分，阐明了27个中药的药效物质基础并丰富了其科学内涵。从具有研究难点的虫类中药中获得450个非肽类小分子，占全球数量的60%，打破了动物药药效物质研究长期以来匮乏的局面，在国内外处于领先地位。以第一或通讯作者在JASN，Org Lett等期刊发表SCI论文72篇；申请专利42项（授权28项）；形成了5个先导化合物和1个具有自主知识产权的候选药物；获2012年广东省科技进步一等奖（第三）。

The applicant’s studies focus on the isolation and identification of bioactive substances from traditional Chinese medicines (TCMs). Although TCMs have been used in clinical practice for centuries, organic compounds responsible for their biological activities remain for the most part unknown. Chronic kidney disease (CKD), for which no effective therapeutic approaches currently exist, is a major disease that causes progressive kidney dysfunction and eventual death. Over the recent five-year period, the investigator’s studies focused on the isolation of compounds from TCMs and evaluation of their activities against CKD. TCM philosophy suggests that “stasis” and “deficiency” are implicated in the pathogenesis of CKD. Thus, “removing stasis” and “tonifying deficiency” are guiding principles in the practice of TCM. Because of this, the investigator has targeted his recent efforts on TCMs that have these properties. Employing multiple strategies, such as dereplication, and guided by TCM theory and bionic ideas, the investigator has selected representative materials such as Resina Toxicodendri, a resin from Toxicodendron vernicifluum used for promoting blood circulation and removing blood stasis, Ganoderma species displaying potent tonic effects and medicinal insects, and has isolated 203 substances that have potent reno-protective effects from TCMs by targeting signaling pathway such as TGF-β/Smads or Wnt/β-catenin. These findings provide sound evidence for the medical applications of 27 TCMs. In addition, 450 insect-derived non-peptide small molecules, accounting for 60% of the total isolated from insects thus far, have been characterized. The investigations have provided deep insight into insect chemicals and will guide future efforts in this field. Thus far, 72 SCI papers on which the applicant is the first or corresponding author have arisen from the investigator’s studies and the work has led to 42 patents including 28 have been authorized. His effort has led to the identification of 5 leading compounds and 1 drug candidate. He also received the first-class scientific and technological progress award of Guangdong Province in 2012 recognizing his achievements in anti-CKD research.

以丹参﹑板蓝根﹑青蒿等重要药用植物为对象，从活性成分的生物合成，转录调控，以及活性成分累积器官的发育等角度开展研究，解析药材品质的遗传机制。在此基础上开展品质调控，将中药质量控制前移至品质设计层次。完成了丹参酚酸B生物合成途径的解析，诠释了菘蓝木脂素类成分的生物合成及调控机制：提出并初步验证“丹参漆酶（Laccase）是催化迷迭香酸生成丹参酚酸B的关键催化酶”假说，对完全植物中酚酸成分生物合成途径具有关键意义。明确了一系列板蓝根木脂素合成途径的特异催化蛋白，通过解析蛋白晶体结构，阐明了结构域特征，解释了其高效催化木脂素转化的机制，为精准开展木脂素类活性成分代谢工程提供了靶点。发现了一系列活性产物合成调控相关的转录因子。首次报道青蒿腺毛特异表达转录调控因子TAR1，具有调控青蒿腺毛发育从而影响腺毛数量，同时对青蒿酸的合成具有关键调控作用；丹参转录因子SmMYC2a及2b对丹参酚酸类和丹参酮合成途径的不同调控作用；板蓝根转录因子IiERF049通过调控水杨酸合成来影响菘蓝木脂素途径。创立了大幅促进丹参酚酸B、落叶松脂素和青蒿素等有效成分积累的技术方法，变“被动筛选”为“主动创制”：构建了丹参CRISPR/Cas9基因编辑系统，该系统将成为开展丹参代谢调控的强效工具。利用蛋白质工程修饰中药药效物质生物合成过程，解析PLR1蛋白结构，V46L定点突变可使催化效率提高约10倍。获得了5个遗传稳定的菘蓝、丹参、黄花蒿优良株系建立药用植物表型组分析平台，实现药材的表型﹑化学特征高通量解析，筛选关键品质特征，获得相关SNP。形成了中药材种苗选育、品质预判、科学栽培的技术体系，板蓝根种质及栽培技术成功实现转换，种植面积25万亩以上。发表研究论文43篇，其中SCI收录论文35篇；申请国家发明专利5项；获教育部科技进步一等奖1项（第一完成人）、国家科技进步二等奖1项（第六完成人）； 国际学术报告6人次；培养博士研究生3名，硕士9名，教育部长江学者奖励计划“青年学者”1名，上海市青年科技启明星2名。