Graduated from the Biology Department of Southwest Normal University in 1995 with a bachelor degree; Graduated from Kunming Institute of Zoology in 2001 with doctorate degree majored in zoology; Post-doctoral research in Biochemistry Department of Liverpool University from 2002 to 2004.

From August 2001 to March 2002, he served as an assistant professor in Kunming Institute of Zoology, Chinese Academy of Sciences; From July 2004 to July 2008, he served as a professor in Kunming Institute of Zoology, Chinese Academy of Sciences; From August 2008 to June 2014, he served as Assistant Director and professor in Kunming Institute of Zoology, Chinese Academy of Sciences; From July 2014 to April 2021, he served as the Deputy Director and professor in Kunming Institute of Zoology, Chinese Academy of Sciences; From May 2021 to now, he served as a professor in Kunming Institute of Zoology, Chinese Academy of Sciences.

He is currently the editorial board member of international publications such as Research, Journal of Venom Research, Toxins, Journal of Pharmacy and Pharmacology, Peptides, Zoological Research, Science China-Life Science and China Natural Medicine. Chairman of the Bio-toxin Professional Committee of the Chinese Society of Toxicology, executive director of the Chinese Society of Zoology, chairman of the Yunnan Society of Experimental Animals, chairman of the Yunnan Society of Biochemistry, Director of Yunnan Key Laboratory for Research and Utilization of Active Peptides, Director of Natural Active Peptide Engineering Laboratory, Chinese Academy of Sciences and Director of the National and Local Joint Engineering Research Center for Natural Active Peptides.

Diversity of animal toxins and their structure-function

Animals such as snakes, scorpions, spiders, wasps, centipedes, cone snails and toads evolved to produce venoms in order to adapt to specific ecological environment and for defense or predation. Animal toxins are with rich diversity, high activity and specificity, which are main reasons why venomous animals have been used in traditional Chinese medicines for thousands of years. These toxins are able to affect the normal function of human body through different physiological and biochemical mechanisms. Animal toxins have become powerful probes to analyze the structure-function of ion channels and receptors. They are also good tools for exploring physiological and pathological mechanisms. At the same time, animal toxins are valuable resources for discovery of innovative drugs. We focus research on discovery of animal toxins, the mechanism underlining their actions, mining of drug leads form toxins, and diagnosis and treatment of bites or stings by venoms animals. Use purification technologies such as activity tracking, molecular sieve chromatography, ion exchange chromatography, high pressure liquid chromatography, and molecular mining technology based on high-throughput bio-molecular interaction detection technology, and use proteomics and high-throughput screening technology to obtain functional active peptides and proteins from toxic animal venom. The biophysical and pharmacological mechanisms of the complex conformational changes in their structure and kinetic characteristics were systematically studied to establish molecular resource database. At the same time, these peptides are carried out for drug evaluation to find candidate drug molecules such as antithrombotic, anti-tumor, analgesic and anti-infection.

 

Ion channel structure-function and animal adaptive evolution

Ion channels are membrane protein molecules that produce bioelectric signals and intracellular calcium signals. Ion channels are various and widely distributed; More than 400 human ion channels have been found to be crucial to all physiological functions of the human body. Disorder of ion channel function and mutation at gene level can lead to a variety of diseases in almost all tissues and organs of human body. Because of their special importance and their relationship with major diseases, ion channels are currently the second drug target in drug development. In the long process of evolution in nature, many animals and plants have produced bioactive molecules that directly act on the ion channels, which are the important material basis for environmental adaptation and the basis for realizing their survival strategies, such as molecular weapons for efficient defense and predation. Peptide toxin molecules in animals (such as snake, scorpion, spider, etc.) and capsaicin in plants are typical examples of specifically acting on ion channels to ensure the adaptation of biological environment. We use pharmacology, electrophysiology and gene knockout/knock-in methods to focus on the activation and deactivation mechanisms of temperature sensing and acid sensing plasma channels. At the same time, the biological significance of ion channel active peptides derived from animal species (centipede and scorpion) with special survival strategies (such as toxic and blood-sucking) for animal survival adaptation was studied to clarify the internal relationship between biological functions and pharmacological functions related to animal survival strategies.

 

Mechanism of cardiovascular, infectious and neurodegenerative diseases and R & D of new drugs

Diseases such as cardiovascular, infectious and neurodegenerative diseases seriously threaten human health, but at present, many clinical treatment drugs have obvious side effects such as bleeding, which seriously restricts the clinical application. Based on the new mechanism of action and new target, the research and development of new low-risk treatment and prevention drugs has a great clinical demand, and is also the main direction of new drug research and development. However, due to the lack of in-depth understanding of the mechanisms of cardiovascular, infectious and neurodegenerative diseases and the lack of breakthroughs in new theories and mechanisms of disease mechanisms, drug design has been seriously restricted. Our work mainly focuses on the mechanism of biological macromolecular complexes in diseases. For example, the interaction between antimicrobial peptides and mitochondrial DNA, the interaction between transferrin and coagulation factors, and the discovery of important molecular cascades that regulate and maintain the homeostasis of coagulation and the complex formed in the process of platelet activation. At the same time, polypeptides from centipede, scorpion, gadfly and other sources are used as "molecular probes" to study the interaction between them and the ion channels and receptors related to the nervous system, blood system and immune system, and their specific functional sites, dynamic characteristics and possible regulatory mechanisms on these ion channels/receptors, so as to further study the pathogenesis of human diseases. We also explore the mechanism of pathogen-host interaction mediated by toxic pathogen vectors using toxins. For example, mosquito salivary toxins assist the transmission mechanism of pathogens, and bat salivary toxins promote the transmission of viruses. Based on the newly discovered mechanism of blood hypercoagulability, platelet membrane receptor complex and signal pathway, we developed new low-risk drug design strategies, designed and synthesized polypeptide molecules and their derivatives. At the same time, we use the established technology system of active molecule mining, drug evaluation and new drug research to carry out the research and development of new drugs such as anti-thrombosis, anti-infection and anti-depression.

1.        Preclinical study of antibacterial peptide ZY13, a new class 1 chemical drug for the treatment of drug-resistant fungal vaginitis

2.        Pharmacochemistry of centipede toxin specific Kv1.3 inhibitor and its molecular mechanism in the treatment of psoriasis

3.        Natural products targeting NMDA receptors and calcium channels in traditional medicine in Southeast Asia and the discovery of drugs for Alzheimer's disease

4.        Preclinical study of class I new drug for ischemic stroke and establishment of natural active peptide molecular resource library

5.        The response of endothermic animals to extreme temperature and its molecular mechanism

6.        Molecular resource bank of toxic medicinal materials and research and development of new drugs in Yunnan

7.        Study on the molecular mechanism of centipede using venom to prey efficiently

8.        Industrialization technology for natural peptides and new product R&D platform

9.        The new mechanism of atherosclerotic disease based on biomolecular complex and the research and development of innovative antithrombotic drugs with high efficiency and low bleeding risk

He has won the second prize of the National Award for Technological Invention (2013), the first prize of the Yunnan Provincial Natural Science Award (2018 and 2008), the second prize of the Chinese Medical Science and Technology Award (2022), the second prize of the Yunnan Provincial Natural Science Award (2009), the National Innovation Award (2017), the Outstanding Contribution Award of the Administration of Traditional Chinese Medicine, the National Administration of Traditional Chinese Medicine, the Outstanding Contribution Award (2017), the Chinese Youth Science and Technology Award (2011), and K. C. Wong Western Scholars Outstanding Contribution Award of the Chinese Academy of Sciences (2010), Outstanding Young Scholars of the Chinese Academy of Sciences (2010), Tan Jiazhen Life Science Innovation Award (2010). In 2022, he was funded by the first "New Cornerstone Researcher Program".

1)        Fang M, Li Y, Liao Z, Wang G, Cao Q, Li Y, Duan Y, Han Y, Deng X, Wu F, Kamau P, Lu Q, Lai Ren. 2023. LBP up-regulation by stress accounts for monoamine insufficiency and depression development. Immunity, in press.

2)        Tian L, Zhang H, Yang S, Luo A, Kamau PM, Hu J, Luo L, Lai Ren. 2023. Vertebrate OTOP1 is also an alkali-activated channel. Nat Commun., 14(1):26.

3)        Li M, Tang X*, Liao Z, Shen C, Cheng R, Fang M, Wang G, Li Y, Tang S, Xie L, Zhang Z, Kamau PM, Mwangi J, Lu Q, Li Y, Wang Y, MacKeigan DT, Cerenzia EGG, Ni H, Lai Ren. 2022. Hypoxia and low temperature up-regulate transferrin to induce hypercoagulability at high altitude. Blood, 140(19):2063-2075.

4)        Fang M, Tang X, Zhang J, Liao Z, Wang G, Cheng R, Zhang Z, Zhao H, Wang J, Tan Z, Kamau PM, Lu Q, Liu Q, Deng G, Lai Ren. 2022. An inhibitor of leukotriene-A4 hydrolase from bat salivary glands facilitates virus infection. Proc Natl Acad Sci U S A., 119(10):e2110647119.

5)        Jin L, Jiang BG, Yin Y, Guo J, Jiang JF, Qi X, Crispell G, Karim S, Cao WC, Lai Ren. 2022. Interference with LTβR signaling by tick saliva facilitates transmission of Lyme disease spirochetes. Proc Natl Acad Sci U S A., 119(47):e2208274119.

6)        Yunfei Wang, Chuanlin Yin, Hao Zhang , Peter Muiruri Kamau , Wenqi Dong, Anna Luo, Longhui Chai, Shilong Yang, Ren Lai. 2022. Venom resistance mechanisms in centipede show tissue specificity. Curr Biol., S0960-9822(22)01079-X.

7)        Wang G, Yang ML, Duan ZL, Liu FL, Jin L, Long CB, Zhang M, Tang XP, Xu L, Li YC, Kamau PM, Yang L, Liu HQ, Xu JW, Chen JK, Zheng YT, Peng XZ, Lai R. Dalbavancin binds ACE2 to block its interaction with SARS-CoV-2 spike protein and is effective in inhibiting SARS-CoV-2 infection in animal models. Cell Res., 31(1):17-24.

8)        Tang X, Zhang Z, Fang M, Han Y, Wang G, Wang S, Xue M, Li Y, Zhang L, Wu J, Yang B, Mwangi J, Lu Q, Du X, Lai Ren. 2020. Transferrin plays a central role in coagulation balance by interacting with clotting factors. Cell Res., 30(2):119-132.

9)        Shen C, Liu M, Xu R, Wang G, Li J, Chen P, Ma W, Mwangi J, Lu Q, Duan Z, Zhang Z, Dahmani FZ, Mackeigan D, Ni H, Lai Ren. 2020. 14-3-3ζ-c-Src-integrin-β3 complex is vital for platelet activation. Blood, 136(8):974-988.

10)     Yang S, Lu X, Wang Y, Xu L, Chen X, Yang F, Lai Ren. 2020. A paradigm of thermal adaptation in penguins and elephants by tuning cold activation in TRPM8. Proc Natl Acad Sci U S A., 117(15):8633-8638.

11)     Yang S, Wang Y, Wang L, Kamau P, Zhang H, Luo A, Lu X, Lai Ren. 2020. Target switch of centipede toxins for antagonistic switch. Sci Adv., 6(32):eabb5734.

12)     Tang X, Fang M, Cheng R, Zhang Z, Wang Y, Shen C, Han Y, Lu Q, Du Y, Liu Y, Sun Z, Zhu L, Mwangi J, Xue M, Long C, Lai Ren. 2020. Iron-Deficiency and Estrogen Are Associated with Ischemic Stroke by Up-Regulating Transferrin to Induce Hypercoagulability. Circ Res., 127(5):651-663.

13)     Yang S, Wang Y, Wang L, Kamau P, Zhang H, Luo A, Lu X, Lai Ren. 2020. Target switch of centipede toxins for antagonistic switch. Sci Adv., 6(32):eabb5734..

14)     Jin L, Guo X, Shen C, Hao X, Sun P, Li P, Xu T, Hu C, Rose O, Zhou H, Yang M, Qin CF, Guo J, Peng H, Zhu M, Cheng G*, Qi X, Lai Ren. 2018. Salivary factor LTRIN from Aedes aegypti facilitates the transmission of Zika virus by interfering with the lymphotoxin-β receptor. Nat Immunol., 19(4):342-353

15)     Zhiye Zhang, Ping Meng, Yajun Han, Chuanbin Shen, Bowen Li, Hakim M.A., Xuguang Zhang, Qiumin Lu, Mingqiang Rong and Ren Lai. 2015. Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition. Immunity, 43:1137-1147.