个人简介

库志强，2005-2010年就读于华中农业大学动物医学专业，获学士学位；2010-2016年就读于中国科学院上海巴斯德研究所，获博士学位；2016-2017年在勃林格殷格翰上海研发中心任科学家；2017年加入德克萨斯大学休斯顿健康科学中心分子医学研究所开展博士后研究工作，随后任讲师；2022年夏季全职加入西湖大学应急医学研究中心、生命科学学院，任博士生导师、助理教授一职。

学术成果及研究方向

库志强博士的研究集中在抗体药物免疫治疗，代表性成果包括：1）针对新冠肺炎，揭示了抗体鸡尾酒抑制病毒逃逸的机制，构建了有效的双特异性抗体，并开发了喷鼻型的广谱中和IgM抗体；2）针对复发性卵巢癌靶点和肿瘤微环境髓系免疫检查点受体靶点，分别开发了治疗性抗体；3）针对手足口病主要病原研究了疫苗和中和抗体，阐述了抗体中和机制。这些研究成果取得了良好的转化，其中新冠肺炎IgM抗体和髓系免疫检查点阻断抗体已转让给生物制药公司，并顺利开展一期临床试验。

实验室将围绕抗体药物的开发和作用机制以及疾病靶点生物学开展基础和转化医学研究，研究方向集中（但不限）于以下几点：

1) 针对传染病和癌症等疾病新靶点开展抗体免疫治疗研究，包括开发不同作用机制的抗体（激活型、抑制型、免疫细胞接合等），设计具有不同结构的抗体（IgG、IgM、双特异性抗体等），以及探索基于抗体的其他新型免疫治疗药物范式（抗体融合蛋白、ADC、CAR-T等）。

2）针对新发和突发病毒性疾病，建立蛋白进化等方法研究病毒重要靶点的发生和演变规律，促进对病毒靶点生物学的理解以及抗体和疫苗等药物的开发。

3）探索细胞外基质重塑在疾病发展中的作用、以及相关靶点的鉴定和治疗药物的开发。

代表论文

(*co-first authors)

1. Ku Z*, Xie X*, Hinton PR*, Liu X*, Ye X, Muruato AE, Ng DC, Biswas S, Zou J, Liu Y, Pandya D, Menachery VD, Rahman S, Cao YA, Deng H, Xiong W, Carlin KB, Liu J, Su H, Haanes EJ, Keyt BA, Zhang N, Carroll SF, Shi PY, An Z. Nasal delivery of an IgM offers broad protection from SARS-CoV-2 variants. Nature. 2021 Jul;595(7869):718-723.

2. Ku Z*, Xie X*, Davidson E, Ye X, Su H, Menachery VD, Li Y, Yuan Z, Zhang X, Muruato AE, I Escuer AG, Tyrell B, Doolan K, Doranz BJ, Wrapp D, Bates PF, McLellan JS, Weiss SR, Zhang N, Shi PY, An Z. Molecular determinants and mechanism for antibody cocktail preventing SARS-CoV-2 escape. Nat Commun. 2021 Jan 20;12(1):469.

3. Ku Z*, Xie X*, Lin J*, Gao P*, El Sahili A, Su H, Liu Y, Ye X, Li X, Fan X, Goh BC, Xiong W, Boyd H, Muruato AE, Deng H, Xia H, Jing Z, Kalveram BK, Menachery VD, Zhang N, Lescar J, Shi PY, An Z. Engineering SARS-CoV-2 cocktail antibodies into a bispecific format improves neutralizing potency and breadth. bioRxiv [Preprint]. 2022 Feb 1:2022.02.01.478504.

4. Geethadevi A*, Nair A*, Parashar D*, Ku Z*, Xiong W, Deng H, Li Y, George J, McAllister DM, Sun Y, Kadamberi IP, Gupta P, Dwinell MB, Bradley WH, Rader JS, Rui H, Schwabe RF, Zhang N, Pradeep S, An Z, Chaluvally-Raghavan P. Oncostatin M Receptor-Targeted Antibodies Suppress STAT3 Signaling and Inhibit Ovarian Cancer Growth. Cancer Res. 2021 Oct 15;81(20):5336-5352.

5. Mishra I*, Duerrschmid C*, Ku Z, He Y, Xie W, Silva ES, Hoffman J, Xin W, Zhang N, Xu Y, An Z, Chopra AR. Asprosin-neutralizing antibodies as a treatment for metabolic syndrome. Elife. 2021 Apr 27;10:e63784.

6. Wang X*, Ku Z*, Zhang X*, Ye X, Chen J, Liu Q, Zhang W, Zhang C, Fu Z, Jin X, Cong Y, Huang Z. Structure, Immunogenicity, and Protective Mechanism of an Engineered Enterovirus 71-Like Particle Vaccine Mimicking 80S Empty Capsid. J Virol. 2017 Dec 14;92(1):e01330-17.

7. Ku Z, Ye X, Shi J, Wang X, Liu Q, Huang Z. Single Neutralizing Monoclonal Antibodies Targeting the VP1 GH Loop of Enterovirus 71 Inhibit both Virus Attachment and Internalization during Viral Entry. J Virol. 2015 Dec;89(23):12084-95.

8. Ku Z, Liu Q, Ye X, Cai Y, Wang X, Shi J, Li D, Jin X, An W, Huang Z. A virus-like particle based bivalent vaccine confers dual protection against enterovirus 71 and coxsackievirus A16 infections in mice. Vaccine. 2014 Jul 23;32(34):4296-303.

专利

1. Ku Z, Zhang N, An Z, Xie X, Shi P. “Antibodies to Coronavirus Spike Protein and Methods of Use”. International Application No. PCT/US2021/028646 based on U.S. Provisional Application No. WO 2021/216876 A2. WO 2021/216876 A3. Licensed to IGM Biosciences.

2. An Z, Zhang N, Ku Z, Zhang C, Liu X, Chen H, Xie J, Costa MJ, Song A, Liao X. “Novel LILRB2 Antibodies and Uses Thereof”. International Patent Publication No. WO 2021/158413 A1. Licensed to Immune-Onc Therapeutics.

3. Zhang N, An Z, Ku Z, Deng H, Lingegoeda SM, Sood KS. “CD5L-BINDING ANTIBODIES AND USES FOR THE SAME”. WO 2021/202908 A1.

4. Zhang N, An Z, Ku Z, Wan Y, Krzeszinski J. “NMES1 Antibodies and Uses and Methods of Use Thereof”. US 2021/0371508 A1

5. Ku Z, Zhang N, An Z, Pradeep S, Chaluvally-Raghavan P. “OSMR-SPECIFIC MONOCLONAL ANTIBODIES AND METHODS OF THEIR USE”. Provisional application filed.

6. Huang Z, Ku Z, Shi J, Liu Q. An anti-enterovirus binding molecules and uses thereof (CN 103421112 B).

全部论文链接

https://pubmed.ncbi.nlm.nih.gov/?term=zhiqiang%20ku&sort=date&size=20

联系方式

电子邮箱：kuzhiqiang@westlake.edu.cn