Li Huashun, male, Han nationality,1born in March, 963, born in Tai 'an, Shandong Province, is a doctor of medicine, doctor of science, doctoral supervisor, stem cell expert, and anti-inflammatory and anti-tumor drug research and development expert. He is currently the chairman, president and chief scientist of ascoli Biotechnology Company. Part-time distinguished researcher of Shanghai Institute of Advanced Studies, Chinese Academy of Sciences; Adjunct Professor, Suzhou Institute of Systems Medicine, China Academy of Medical Sciences. Since returning to China in July 2007, I have undertaken seven national scientific research projects as the project leader, all of which are major scientific research projects of the Ministry of Science and Technology (project number: 2007CB947202；; 2009 CB 94 1402； 2009r0022014cb964600) and the National Natural Science Foundation (Project No.30771102; 3 107 1283), and served as the chief scientist of the national major new drug creation project (20 13ZX09509 104), focusing on anti-cancer and anti-inflammatory protein drugs and cell drugs.
Chinese name: Li Huashun.
Mbth: Huashunli
Nationality: China.
Ethnic group: Han nationality
Place of Birth: Tai 'an City, Shandong Province
Date of birth:1March 963
Occupation: scientist, doctor
Graduate institutions: Shanghai Second Military Medical University and Washington University St. Louis.
Faith: Historical Materialism and Dialectical Materialism
Main achievements: CAR-NK tumor immune cell therapy
Anti-cancer and anti-inflammatory protein drugs
Asymmetric cell division
Bite bispecific antibody drug
Nerve axon orientation, cell migration
Masterpieces: cell, neuron, neuron, natural neuroscience, gene &; Develop, develop
Gender: male
Title: Professor
Position: Chairman and President of ascoli Biotechnology Company.
personal record
Li Huashun, male, was born in Tai 'an City, Shandong Province in March of 198 1, graduated from the middle school affiliated to Shandong Normal University, and received a bachelor's degree in medicine from the Second Military Medical University of China People's Liberation Army 198 1 986. 1989 to 199 1, doctor of the 306th hospital of China People's Liberation Army; 199 1 to 1994, visiting scholar at Johns Hopkins University, USA; From 1994 to 1999, Washington University in St. Louis is Rao Yi's laboratory. 1999 From 2005, the University of California, San Francisco worked as a postdoctoral fellow in the laboratories of LilyYehJan and Jan, Yu Hung (Yunong Zhan), and served as a tenured assistant professor in the Institute of Molecular Medicine and Genetics of Georgia Medical College from 2005 to 2007. 2007-20 12, distinguished professor, researcher of developmental cell biology, director of West China Institute of Developmental Stem Cells, Sichuan University. 20 13-20 15, distinguished professor, Tongji University, Distinguished Researcher, Institute of Advanced Translational Medicine. 20 13 to present, chairman, president and chief scientist of ascoli (Suzhou) Biotechnology Co., Ltd.; Part-time distinguished researcher of Shanghai Institute of Advanced Studies, Chinese Academy of Sciences. Adjunct Professor, Suzhou Institute of Systems Medicine, China Academy of Medical Sciences.
Dr. Li Huashun revealed the relationship between retina and lens development in his academic achievement (1). 2) Reveal the mechanism of binocular development; 3) Revealing the molecular mechanism of axon orientation; 4) Revealing the molecular mechanism of neuron migration; 5) Revealing the molecular mechanism of asymmetric division of neural stem cells; 6) The recovery mechanism of vesicular fusion molecules was revealed. Dr. Li Huashun's main research interests are developmental cell biology, development and industrialization of anti-tumor and anti-inflammatory proteins and cell drugs. He has more than 30 years of scientific research experience in this field, and has been working on cells, neurons, genes & Development, nature neuroscience, Development and other top international magazines have published 30 papers, which have been cited by him for more than 3,000 times. Since I returned to China in July 2007, I have undertaken seven national scientific research projects as the project leader, namely, China Minsheng Investment Corporation and major scientific research projects of the Ministry of Science and Technology (project number: 2007CB947202；; 2009 CB 94 1402； 2009r0022014cb964600) and the National Natural Science Foundation (ProjectNo.: 30771102; 3 107 1283), a key R&D project in Jiangsu province (project number: BE20 16677), and served as the chief of the national major new drug creation project (20 13ZX09509 104). Dr. Li Huashun has made outstanding achievements in axonal orientation, nerve cell migration, tumor cell migration, asymmetric division of neural stem cells, CAR-T/CAR-NK anti-tumor cell drugs, anti-inflammatory and anti-tumor bispecific anti-tumor drugs and so on, and is in a leading position in the world. Since the company was established in February, 2013,65438, with the special support of the national major new drug creation, it has applied for and obtained more than 50 invention patents, including 14 global invention patents, and developed a variety of CAR-NK anti-tumor cell drugs, bispecific antibody anti-tumor protein drugs and long-acting fusion protein anti-sepsis and anti-inflammatory drugs. Dr. Li Huashun's invention will bring hope for the healthy recovery of patients with severe cancer and inflammation.
Business experience
198 1- 1986: a student from the Department of Marine Medicine, Second Military Medical University of China People's Liberation Army.
1986- 1989: Master's degree student in General Hospital of Chinese People's Liberation Army.
1989- 199 1: researcher of the 306th hospital of China People's Liberation Army.
199 1- 1994: Visiting Scholar, Johns Hopkins University, USA.
1994- 1999: Ph.D. student, Washington university, St. Louis, USA
1999-2005: postdoctoral fellow, University of California, San Francisco.
2005-2007: Assistant Professor of Life Series at Georgia Medical College, USA.
2007-20 12: Outstanding Professor of Sichuan University
20 13-20 14: Director of the Center for Stem Cell Engineering and Translational Medicine, Dongfang Hospital, Tongji University, China Academy of Sciences.
20 13-20 15: distinguished professor, Institute of Advanced Translational Medicine, Tongji University.
20 13- present: chairman, president and chief scientist of ascoli biotechnology co., ltd.
20 13 till now: part-time distinguished researcher of Shanghai Institute of Advanced Studies, Chinese Academy of Sciences.
20 17 Up to now: Adjunct Professor, Suzhou Institute of Systems Medicine, China Academy of Medical Sciences.
Awards and honors
fightforsightpostdoctoralfellowship 1993- 1994
viktorhamburgerawardindevelopmental biology 1997
the university of washington school of medicine
spencert . and annw . Olin medical science fellowship 1998- 1999
the university of washington school of medicine
2000-2003 National Research Service Award
National institute of health
Leading talents in science and technology in Suzhou Industrial Park 20 13
Suzhou Gusu Innovation and Entrepreneurship Leader 20 15
Academic part-time job
2007-Member of Chinese Society of Neuroscience.
Member of China Society of Cell Biology since 2007.
20 19- Member of China Pharmaceutical Biotechnology Association.
2000-Member of American Society for Neuroscience.
2000-Member of American Society of Cell Biology.
research direction
Asymmetric cell division
This paper mainly studies the asymmetric cell division of neural stem cells and the directional differentiation of stem cell immune cells. These research results have been published in the world famous academic journals Nature Neuroscience, Neuron, Cell, Gene &; Development, development, cell report, etc. Among them, the cumulative impact factor of articles published by the first author or correspondent reaches 96, and * * * has been cited more than 3000 times. After returning to China, he served as distinguished professor of Sichuan University, Director of West China Institute of Developmental Stem Cells, Distinguished Research Fellow of Advanced Research in Translational Medicine of Tongji University, Professor of Medical College of Tongji University, and Director of Translational Medicine Center of Stem Cell Engineering of Oriental Hospital of Tongji University, and continued to study the molecular mechanism of asymmetric cell division of stem cells. It has undertaken a series of scientific research projects, such as major scientific research plans of the Ministry of Science and Technology, general projects of natural funds and international cooperation.
Research and development of anti-tumor drugs
The discovery of axonal director is considered as a major breakthrough in neurodevelopmental biology after 198 1 RogerSperry, winner of the Nobel Prize in Physiology and Medicine, put forward the "chemical affinity hypothesis". Dr. Li Huashun discovered the neurodirectional factor in the laboratory of Professor Rao Yi of the University of Washington, USA, and published the same issue of Cell (Cell 96,807-818+08, 1999) with Professor CoreyGoodman, a famous scientist who teaches at the University of California at Berkeley, and Professor MarcTessier-Lavigne, a famous scientist who teaches at the University of California at San Francisco. Subsequently, it was found that this signaling pathway was closely related to the metastasis of malignant tumor cells and the infiltration of inflammatory cells. Based on this new mechanism, the project "Research and Development of New Drugs Based on Targeted Molecules" is listed as a major national new drug creation project (2013ZX095091043048 RMB). With the support of this project, long-acting anti-inflammatory and anti-tumor drugs have been developed, which have obvious effects in inhibiting the metastasis of non-small cell lung cancer, liver cancer, pancreatic cancer and astrocytoma, and treating sepsis and pulmonary fibrosis. The drug has broad-spectrum anti-tumor metastasis and non-bacterial inflammation, which will greatly improve and improve the quality of life of patients.
Tumor immune cell therapy
New therapeutic techniques, such as chimeric antigen receptor T cell therapy (CAR-T cell therapy) and immune checkpoint blocking therapy, have achieved unprecedented results, which undoubtedly established their position as an important means of cancer treatment. CAR-T cell therapy is a therapeutic method to specifically remove cancer cells by autologous T cells under the guidance of chimeric antigen receptors. This therapy has achieved remarkable results in the treatment of hematological malignancies: the complete remission rate of acute lymphoblastic leukemia is over 90%, and the complete remission rate of chronic lymphoblastic leukemia and lymphoma is over 50%. Some patients did not relapse for several years after CAR-T cell therapy, showing signs of cure. Immune checkpoint blocking therapy is a cancer treatment method, which uses monoclonal antibodies to release brakes that inhibit T cell function-molecules that inhibit T cell activation on immune cells and cancer cells-to restore the anti-tumor activity of T cells. This therapy can cause lasting anti-tumor response and long-term remission.
CAR-T cell therapy and immune checkpoint blocking therapy not only have obvious therapeutic effects, but also have their shortcomings. The absence of CAR-T cells, including 1) has not made a breakthrough in the treatment of solid tumors; 2) The side effects are great, especially the probability of severe cytokine storm is high; 3) Individualized treatment can't be scaled up and the cost is high. The main deficiency of immune checkpoint blocking therapy is that the clinical response rate of different tumors is quite different, and the response rate of some tumors is low, and only a few patients can benefit from the treatment.
To solve these problems, the team led by Dr. Li Huashun took the lead in developing BiCAR technology in the world by using cutting-edge synthetic biology technology and artificial intelligence evolutionary screening engineering technology, which greatly promoted the development of immunotherapy.
BiCAR technology constructs chimeric antigen receptor and immune checkpoint blocking molecule on the same vector, and uses this vector to transform T cells or NK cells, so the obtained CAR-T/NK cells are BiCAR-T/NK cells. Compared with single CAR-T/NK cell therapy and immune checkpoint blocking therapy, BiCAR-T/NK cell therapy has obvious advantages:
1.BiCAR-NK cells overcome the defects of individualized treatment.
CAR-T technology needs to draw blood from patients, isolate T lymphocytes in vitro, activate, transduce and culture. First, the culture time is long, which takes 2-3 weeks. Second, the quality of patients' T lymphocytes is poor, and more than 50% of patients' T lymphocytes are not easy to transduce carriers with CAR. BiCAR-NK is an engineered NK cell, which can be used immediately without autologous cells. Generally, cancer patients belong to "emergency", especially those who relapse after surgery and chemotherapy. Tumor cells are multiplying every day and need immediate treatment. BiCAR-NK's "immediacy" solves this problem.
2.CAR-T/NK therapy combined with immune checkpoint blocking therapy overcomes the limitations of single drug therapy.
First of all, combination therapy overcomes the limitations of antibody drug therapy. Intravenous antibody drugs have short metabolic cycle in vivo, low bioavailability, need to be administered many times, and have great side effects after systemic administration. BiCAR-T/NK cells deliver antibody drugs directly to tumor sites, which greatly improves the bioavailability, and continues to produce with the proliferation of CAR-T/NK cells, playing a lasting role.
Secondly, combined therapy can greatly promote the anti-tumor effect of CAR-T/NK cells. CAR-T cells are inhibited by immunosuppressant cells and cytokines after entering tumors, and cannot achieve anti-tumor effect. When BiCAR molecules enter the tumor, these inhibitory effects can be relieved, which can not only make CAR-T function normally, but also mobilize all immune cells in the body, concentrate superior forces and annihilate tumor cells in one fell swoop.
Main contribution
1. Leeds, Zhang, Linz, Houke, Zhang, Meni, Li, Gao. (20 16). lgl 1 isrequiredforlfactionanddevelopmentofilfactorybulbinmices。 PLoS one . 1 1(9):e 0 162 126。
2.(20 16)。 The epithelial-mesenchymal transition of triple negative breast cancer is negatively regulated by antagonistic signal transduction. onco target 7(38):6 1036-6 1053。
3.(20 16)。 The subunit α of G protein is necessary for craniofacial morphogenesis. PLoS on 1 1(2):e 0 147535。
4. Shao, X, Liu, Y, Yu, Q, Ding, Z, Qian, W, Zhang, L, Zhang, J and Jiang. , N, Gui, L, Xu, Z, Hong, Y, Ma, Y, Wei, Y, Liu, X, Jiang, C, Zhu, M, Li, H, Li, H, S. Mobile phone search 26:593-6 12
5. (2016) Liu, Wang, Lei, Li, Zhang, Wu, An, Zhang, Zhu, Mi, Xu, Zhu, Hong, Wang, Shen, Yang, Li, Li, Li. scireportsfeb 16； 6:2 10 19 . doi: 10. 1038/srep 2 10 1。
6. Jiang, Wang, Xie, Zhou, Su, Li, Wang, Shen. (2065 438+06). down regulationofglutamatetransportereaat 4 byconditionalknockoutofrheb 1 incerebellapurkinjecells。 Cerebellum 15:3 14-2 1
7.HeQ，YanH，WoD，LiuJ，LiuP，ZhangJ，LiL，ZhouB，GeJ，LiH，LiuS，Zhu。 (2065 438+06). Wnt 3 asuppresseswnt/β-cateninsignationcancercellproliferation followingserumdeprivation。 exp cellres 34 1:32-4 1。
8. Shao, X, Liu, K, Fan, Y, Ding, Z, Chen, M, Zhu, M, Weinstein, L.S, Li, h .(20 15)gα serine protease inhibitor-1- phosphate receptor/. Journal of GeneticsandGenomics
9. Liu, Lin, Qin, Wei, Yang, He, Shao, Ding, Zhang, Zhu and Li. Weinstein, Liu Xiaosong, Hong, Li, Xing Zhong. ，andLi，HS。 (20 15). gαsregulatesasymmetriccelldivisionofcorticalprogenitorsbycontrolingnummediatednotchingsuppression。 Neuroscience Newsletter 597:97- 103
10.MenY，ZhangA，LiH，JinY，SunX，LiH，GaoJ。 (20 15). lkb 1 regulatescereballdevelopment bycontrollingsonichedgehog-mediated granulecellprecursorproliferationandgranulecellmigration。 Science report 5: 16232.
1 1.MenY，ZhangA，LiH，ZhangT，JinY，LiH，ZhangJ，GaoJ。 (20 15)lkb 1 isrequired forsedevelopmentandmaintenance of stereociliainnerearhaircellsinmices。 PLoS on 10(8):20 13584 1
12. Wang, Cui, Feng, Li and Hu. (20 15). roleofnumbexpressionandnucleartranslocationinendometrialcaner . oncolett 9: 153 1- 1536
13. Hou Chunhua, Ding, Li, Zhang, Jin, Sun Chunhua, Li, Zhao, Sun, Zhang, Zhang, Li ... (20 14). Cerebellar dysplasia and Purkinje CellDefectSinlgl1-Pax 2 conditional knockout mice. Developmental Biology (14)00343- 1
14. Sun Chunchun, Zhao Jun, Jin Yuying, Hou Chunchun, Zong Wenwei, Lu, Gao. (20 14). It regulates the proliferation and differentiation of audio progenitor cells through /PI3K/Akt- signaling pathway. Neurological report. 25: 177-83
15.(20 13)。 Immune-related tpase irgm 1 aggravates experimental acute immune encephalomyelitis by promoting the destruction of blood-brain barrier and blood-brain barrier. Molecular immunology 53:43-5 1
16. Yang, Tian, Sun, Yang, Zhang, Zhu, Shi, Li. , Xu, *. (2012). Poshlocalizesacactivedrac1controls the formation of cell cytoplasm, heleadingprocess and neuronalmigration. CellReports2:640-65 1。 * Co-correspondent.
17. Sun Yuying, Fei, Yang, Zhang, Chen Yuying, Li, Xu Hansheng, (20 10). suppressionfcrmp 2 expression BMP-smadgradientsignallingcontrolsmultiplestageofneuronaldevelopment。 Journal of biochemistry 285:39039-50.
18. Rahimr, Ga Zuraw, Breniji, Kuanji, Johansson Mbu, Liu Chen, Li Shi, Zhan Li, Jenning, Rakip, sestan En. (2007).numbandnumblarequiredformmaintenance of cadherin-based adhesionandpolarityofneuralprogrons。 natneurosci . 10:8 19-27。
19. Huang, Li Aijun, Li Haisheng, Tang, Luo Aijun, Wiggins, Ako, Neve, Li Ruilin, Zhong, Wang Wenwei, Yang Liyuan, Yang Yuanning (2005). Target deletion number
20. Li Haisheng, Wang, Ding, Shen, Qin, Xiao Neiman, MD, J.A., Jones, K.R., Temple, S., Yang, L.Y., Yang, Y.N.(2003).
2 1. Chen Jianhui, Wu Wenwei, Li Haisheng, Fagali, Zhou Tielin, Wu Jianying, Lao, Yang (2000). Expression of embryonic nerve and extracellular secretion. Neuroscience 96,231-6.
22. Zhu, Y*. Li, Zhou Haipeng *. Zhou, Li, Wu, Yao Junying, Yao Yuying (1999). Neuron molecules guide the migration of neurons out of the cortex. Journal of Neurology, 23,473-85. * These authors contribute equally.
23. Li, H-S*. , Chen, J-H*. , Wu, W*. , Fagali, Zhou, L, Yuan, W, Dupers, S, Jiang, Z-H, Nash, W, C, Ornitz, D.M., Wu. J.Y.andRao, Y.( 1999) Slit of vertebrates, Ascreted Ligandfortetransbranepropertinound About, isapretent for lfactory bulb axons. Cell96，807-8 18。 * These authors contribute equally.
24. Li, Liu Hongsheng, Li Hongsheng, Li Tienan, Wen, Wu, Liu Jianyu, Huang (1997).
25.t. belecky-Adams, s. toma rev, Li, H-S, Ploder, L., R.R., o. and Adler, R.( 1997). Pax-6, Prox 1 and CHX10 homeboxgenerrexpressioncorrelations with phenotype fateofretinalprecursorcells. investhomethyllvisualscience . 38: 1293-303。
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