张令强 Lingqiang Zhang

张令强研究员，博士生导师，国家蛋白质科学中心（北京）主体设施主任，医学蛋白质组全国重点实验室常务副主任，国家杰出青年科学基金获得者，获谈家桢生命科学奖创新奖、树兰医学奖青年奖等，入选国家万人计划领军人才、国家百千万人才工程。主要研究方向为蛋白质泛素化修饰与疾病的发生机理与治疗。研究团队综合运用新一代生命组学（蛋白质组学、修饰组学、转录组学等）技术，揭示了Smurf1家族泛素连接酶的特异性激活机制，发现Smurf1家族修饰泛素化与拟素化的一酶双能特征，鉴定Smurf1及其辅激活因子CKIP-1是潜在的疾病治疗靶点，研发了靶向CKIP-1的干扰小核酸及靶向Smurf1的PROTAC降解剂，提出骨质疏松症的促骨形成治疗、KRAS突变难治性结直肠癌的抗修饰治疗新策略；解析了OTU家族去泛素化酶系列成员的新功能新机制，为理解血管发生、肿瘤进展的机理提供了新认识；揭示抑癌蛋白PTEN的泛素化降解和拟素化失活（PTM二次打击）是PTEN低频突变肿瘤类型中肿瘤发生的重要机制。

Researcher Zhang Lingqiang, Doctoral Supervisor, Director of the Main Facility at the National Center for Protein Sciences (Beijing), Executive Deputy Director of the National Key Laboratory of Medical Proteomics, recipient of the National Science Fund for Distinguished Young Scholars, recipient of the Tan Jiazhen Life Science Innovation Award and Shulan Medicine Young Award, selected for the National Ten Thousand Talents Program Leading Talents and the National Millions of Talents Project. The main research direction is protein ubiquitination modification and the pathogenesis and treatment of diseases. The research team comprehensively uses next-generation omics (proteomics, modification omics, transcriptomics, etc.) technologies to reveal the specific activation mechanism of the Smurf1 family ubiquitin ligase, discovered the dual enzymatic function of the Smurf1 family modification ubiquitination and SUMOylation, identified Smurf1 and its co-activator CKIP-1 as potential disease treatment targets, developed interfering small nucleic acids targeting CKIP-1 and PROTAC degraders targeting Smurf1, proposed new strategies for bone formation-promoting treatment of osteoporosis and anti-modification treatment of KRAS mutation refractory colorectal cancer; analyzed the new functions and mechanisms of members of the OTU family deubiquitinase series, providing new insights for understanding the mechanisms of angiogenesis and tumor progression; revealed that ubiquitination degradation and SUMOylation inactivation (PTM double hit) of tumor suppressor protein PTEN is an important mechanism of tumorigenesis in PTEN low-frequency mutation tumor types.