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何永捍   研究员
衰老调控与功能研究学科组
职  务: 衰老调控与功能研究学科组 负责人
学  历:
电  话: +86-871-65118976
传  真:
电子邮件: heyonghan@mail.kiz.ac.cn
通讯地址: 云南省昆明市盘龙区龙欣路17号    650201
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  简  历

  何永捍,医学博士,研究员,博士生导师。长期从事衰老及衰老相关疾病的功能学研究和活性小分子药物研发,已在Nature Communications、Journal of Hematology & Oncology、Aging Cell、Genome Research等国际核心刊物上发表学术论文80余篇;作为核心发明人申请抗衰老和抗肿瘤小分子PCT专利3项;参编衰老研究著作《Senolytics in Disease, Ageing and Longevity》;承担国家重点研发(课题骨干)、国家自然科学基金、云南省基础研究等科研/人才项目10余项;担任《The Innovation》、《Aging and Disease》及《Current Cancer Drug Targets》等杂志编委/青年编委。

 

学习和研究经历

2020.10 - 至今       中国科学院昆明动物研究所,研究员

2018.06 - 2020.09 美国佛罗里达大学(UF),药学博士后

2016.10 - 2018.05 美国阿肯色医科大学(UAMS),药学博士后

2013.01 - 2016.09 中国科学院昆明动物研究所,助理研究员、副研究员

2011.09 - 2012.09 加拿大国家研究委员会(NRC),中加联合培养博士

2007.09 - 2012.12 哈尔滨医科大学,医学博士学位

2002.09 - 2007.07 哈尔滨医科大学,医学学士学位

  

  研究方向

  衰老是一个极其复杂的生物学性状,是衰老相关疾病的独立危险因素。个体微环境的紊乱及对生存环境的不适应均可促发衰老。因此,研究衰老的调控机制、开发有效的抗衰老手段,对认识衰老的本质、防治衰老相关疾病及捍卫国防生态安全均具有重大的科学和战略意义。课题组重点开展的研究方向有:

  1衰老监测和调控机制解析:识别和利用衰老的生物学表征(细胞衰老、慢性炎症、干细胞耗竭、线粒体功能紊乱等)丈量衰老的速率是衰老研究的重要内容。我们通过基因工程及药理学手段,对重要的衰老表征进行可视化示踪,实现个体、器官和细胞衰老的动态监测(Aging Cell. 2019Aging Cell. 2023);利用单细胞组学、分子生物学和功能学手段,构建动物和人体衰老的关键调控网络(Genome Res. 2018),解析衰老及相关生物学性状(如肿瘤、低氧适应等)背后的调控机制(Theranostics. 2017J Hematol Oncol. 2020a)。

  2衰老干预靶点挖掘:以细胞、线虫、小鼠和灵长类为主要研究对象,利用多种方式(自然衰老、物理和化学诱导衰老、癌基因诱导和早衰症)创建衰老和相关疾病模型(器官纤维化和糖脂代谢紊乱疾病模型),挖掘可用于衰老及相关疾病干预的有效靶点(Nat Commun. 2020Aging Dis. 2023)。

  3抗衰老药物开发:清除个体异常累积的衰老细胞被证明可有效延缓衰老、降低衰老相关疾病的发生并最终延长健康寿命。我们利用蛋白靶向降解嵌合体(PROTAC)技术(Oncogene. 2020Eur J Med Chem. 2020)、前药(Prodrug)技术以及生物免疫(如CAR-T)技术开发能有效清除衰老细胞的senolytic小分子/策略(Mech Ageing Dev. 2021);同时基于衰老细胞模型,结合人工智能和功能学手段,从天然活性产物、小分子化合物库中筛选全新的抗衰老小分子(Mech Ageing Dev. 2019)。

  4抗衰老药物在老年疾病和极端环境适应中的应用:衰老和老年疾病互为因果,相辅相成,共享多个分子途径和功能靶点,因此抗衰老药物往往可有效地防治衰老相关疾病。我们主要以肿瘤(J Hematol Oncol. 2020b)、老年纤维化疾病(Transl Res. 2019)和II型糖尿病等为老年疾病模型,以及低氧胁迫等极端环境诱导的动物模型,利用上述抗衰老药物进行干预,开发能有效防治老年疾病和促进极端环境适应的先导化合物。

  承担科研项目

[1] 云南省“兴滇英才支持计划”项目,基于衰老细胞死亡耐受机制开发新的抗衰老策略,2023-2027,在研,主持

[2] 中国科学院率先行动“引才计划”青年项目,2022-2024,在研,主持

[3] 云南省基础研究计划重点项目,202201AS070038p53相关长链非编码RNA-LINC01021调控衰老的作用和机制研究,2022-2025,在研,主持

[4] 国家自然科学基金面上项目,82171558,衰老细胞特异高表达lncRNA-PURPL调控衰老的作用和机制研究,2022-2025,在研,主持

[5] 中国科学院A类战略性先导科技专项“泛第三极环境变化与绿色丝绸之路建设”项目子课题,2018-2023,结题,课题骨干

[6] 国家自然科学基金面上项目,81671404,长寿人群特异低表达基因-甲状腺素转运蛋白MCT10调控衰老的作用机制研究,2017-2020,结题,主持

[7] 云南省应用基础研究计划重点项目,2017FA038,甲状腺素转运蛋白影响衰老/寿命的作用及机制研究,2017-2020,结题,主持

[8] 国家自然科学基金青年基金项目,81500670,热休克蛋白 70HSP-70)在肥胖发生中的作用和机制研究,2016-2018,结题,主持

[9] 中科院青年创新促进会项目,2016-2019,结题,主持

[10] 中科院西部之光“西部博士”项目,2014-2017,结题,主持

[11] 云南省应用基础研究计划面上项目,2013FB069,中国人群长寿相关DNA甲基化调控位点的筛查和功能研究,2013-2016,结题,主持

[12] 国家重点基础研究发展计划(973计划)项目,2013CB530802,“内脏器官衰老与相关老年疾病防治的基础研究”子课题,2013-2017,结题,课题骨干

  专家类别
研究员
  社会任职

20235-至今,《Aging and Disease》青年编委

202210-至今,《The Innovation》青年编委

20205-至今,《Current Cancer Drug Targets》编委

20212-至今,中国老年医学学会-基础与转化医学分会委员

20215-至今,中国生物物理学会-衰老生物学分会委员

202010-至今,中国营养学会-营养与组学分会常务委员

  获奖及荣誉

2023 云南省引进高层次人才(“兴滇英才支持计划”)

2022 中国科学院引进海外高层次人才(中国科学院率先行动“引才计划”)

2020 美国血液协会第61届学术年会研究报告成就奖

2016 中国科学院青年创新促进会会员

2013 黑龙江省高校科学技术一等奖

2013 黑龙江省科技进步二等奖

  代表论著

代表论著 (#共同一作,*共同通讯)

 

2023

[1]  Hu L#, Dong CJ#, Wang Z, He SY, Yang YW, Zi MT, Li HQ, Zhang YH, Chen CJ, Zheng RZ, Jia ST, Liu J, Zhang X*, He YH*. A rationally designed fluorescence probe achieves highly specific and long-term detection of senescence in vitro and in vivo. Aging Cell. 2023; e13896.

[2]  Huang YQ#, Ge MX#, Li YH#, Li JL, Yu Q, Xiao FH, Ao HS, Yang LQ, Li J*, He YH*, Kong QP*. Longevity-associated transcription factor ATF7 promotes healthspan by suppressing cellular senescence and systematic inflammation. Aging and disease. 2023; doi: 10.14336/AD.2022.1217.

[3]  Xiao FH#, Wang HT#, Chen XQ, Ge MX, Yan DJ, Yang XL, Lin R, Guo RH, Zhang W, Tang NLS, He YH, Zhou JM, Cai WW*, Kong QP*. Hypermethylation in H3K9me3 regions characterizes the centenarian methylomes in healthy aging. National Science Review. 2023; 10(6): nwad067.

 

2022

[1]  Guo LY#, Chen YJ#, Li HQ, Yin FQ, Ge MX, Hu L, Zi MT, Qin ZH, He YH*. Telomere length is maternally inherited and associated with lipid metabolism in Chinese population. Aging-US. 2022; 14(1):354-367.

[2]  Hu L#, Li HQ#, Zi MT, Li W, Liu J, Yang Y, Zhou DH, Kong QP, Zhang YX*, He YH*. Why senescent cells (SnCs) are resistant to apoptosis: An insight for senolytic development. Frontiers in Cell and Developmental Biology. 2022; 10:822816.

[3]  Xiao FH#, Yu Q#, Deng ZL#, Yang K, Ye YS, Ge MX, Yan DJ, Wang HT, Chen XQ, Yang LQ, Yang BY, Lin R, Zhang W, Yang XL, Dong L, He YH, Zhou JM, Cai WW*, Li Ji*, Kong QP*. ETS1 acts as a regulator of human healthy aging via decreasing ribosomal activity. Science Advances. 2022; 8(17):eabf2017.

 

2021

[1] Ge MX, Hu L, Ao HS, Zi MT, Kong QP*, He YH*. Senolytic targets and new strategies for clearing senescent cells. Mechanisms of Ageing and Development. 2021; 195:111468.

[2]  He YH*,#, Li W*, Zhang JL, Yang Y, Qian YW, Zhou DH. The curcumin analog EF24 is highly active against chemotherapy-resistant melanoma cells. Current Cancer Drug Targets. 2021; 21(7):608-618.

 

2020

[1]  He YH#, Zhang X(uan)#, Chang JH#, Kim H#, Zhang PY, Wang YY, Khan Sajid, Liu XG, Zhang X(in), Lv DW, Li W, Thummuri Dinesh, Yuan YX, Elisseeff Jennifer, Campisi Judith, Almeida Maria, Song L, Zheng GR*, Zhou DH*. Using Proteolysis-Targeting Chimera Technology to Reduce Navitoclax Platelet Toxicity and Improve Its Senolytic Activity. Nature Communications. 2020; 11(1):1996.

[2]  He YH, Koch R, Budamagunta V, Zhang PY, Zhang X(uan), Khan S, Thummuri D, Ortiz Y. T, Zhang X(in), Lv DW, Wiegand J. S, Li W, Palmer A. C, Zheng GR, Weinstock D. M*, Zhou DH*. DT2216–a Bcl-xL specific degrader is highly active against Bcl-xL-dependent T-cell lymphomas. Journal of Hematology & Oncology. 2020; 13(1):95.

[3] He YH, Wen Li, Lv DW, Zhang Xin, Zhang X, Campisi Judith, Zheng GR, Zhou DH*. Inhibition of USP7 activity selectively eliminates senescent cells in part via restoration of p53 activity. Aging Cell. 2020; 19(3):e13117.

[4] He YH#, Khan S#, Huo ZG, Lv DW, Zhang X, Liu XG, Yuan YX, Hromas R, Xu MJ, Zheng GR, Zhou DH. Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies. Journal of Hematology & Oncology. 2020; 13(1):103.

[5] He YH, Zheng GR, Zhou DH. Senolytic Drug Development. In: Senolytics in Disease, Ageing and Longevity. Healthy Ageing and Longevity. Springer, Cham. 2020; 11. doi: 10.1007/978-3-030-44903-2_1 (Book chapter)

[6]  Khan S#, He YH#, Zhang X, Yuan YX, Pu SY, Kong QP, Zheng GR, Zhou DH*. PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics. Oncogene. 2020; 39(26):4909-4924.

[7]  Zhang X#, He YH#, Zhang PY#, Budamagunta V, Lv DW, Thummuri D, Yang Y, Pei J, Yuan YX, Zhou DH*, Zheng GR*. Discovery of IAP-Recruiting BCL-XL PROTACs as Potent Degraders across Multiple Cancer Cell Lines. European Journal of Medicinal Chemistry. 2020; 199:112397.

[8] Kim HN, Xiong JH, MacLeod RS, Iyer S, Fujiwara Y, Cawley KM, Han L, He YH, Thostenson JD, Ferreira E, Jilka RL, Zhou DH, Almeida M, O'Brien CA. Osteocyte RANKL is required for cortical bone loss with age and is induced by senescence. JCI Insight. 2020; 5(19):e138815.

 

2019

[1]  Khan Sajid#, Zhang X#, Lv DW#, Zhang Q, He YH, Zhang PY, Yuan YX, Liu XG, Thummuri Dinesh, Wiegand Janet, Ferrando Adolfo, Hromas Robert, Konopleva Maria, Zheng GR*, Zhou DH*. A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity. Nature Medicine. 2019; 25(12):1938-1947.

[2]  He YH, Thummuri D, Zheng GR, Okunieff P, Citrin DE, Vujaskovic Z, Zhou DH*. Cellular Senescence and Radiation-induced Pulmonary Fibrosis. Translational Research. 2019; 209:14-21.

[3]  Yu Q, Pu SY, Wu H, Chen XQ, Jiang JJ, Gu KS, He YH*, Kong QP*. TICRR Contributes to Tumorigenesis through Accelerating DNA Replication in Cancers. Front Oncol. 2019; 9:516.

[4]  Li W#, Qin L#, Feng RN, Hu GR, Sun H, He YH*, RP Zhang*. Emerging senolytic agents derived from natural products. Mechanisms of Ageing and Development. 2019; 181:1-6.

 

2018

[1]  Xiao FH#, Chen XQ#, Yu Q#, Ye YS#, Liu YW, Yan DJ, Yang LQ, Chen GJ, Lin R, Yang LP, Liao XP, Zhang W, Zhang W, Wang XF, Zhou JM*, Cai WW*, He YH*, Kong QP*. Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians. Genome Research. 2018; 28(11):1601-1610.

[2]  He YH*, Li Wen, Hu GR, Kong QP. Bioactivities of EF24, a novel curcumin analog: A review. Frontiers in Oncology. Front Oncol. 2018; 11(8):614.

[3]  Yuan LF, Zhai LH, Qian LL, Huang D, Ding Y, Xiang HD, Dr. Liu XJ, Thompson W, Liu J, He YH, Chen XQ, Hu J, Kong QP, Tan MJ, Wang XF*. Switching off IMMP2L Signaling Drives Senescence via Simultaneous Metabolic Alteration and Blockage of Cell Death. Cell Research. 2018; 28(6):625-643.

[4]  Zhang X, Zhang SP, Liu XG, Wang YY, Chang JH, Zhang X, Mackintosh S, Tackett A, He YH, Lv DW, Laberge RM, Campisi J, Wang JR, Zheng GR, Zhou DH*. Oxidation resistance 1 is a novel senolytic target. Aging Cell. 2018; 17(4):e12780.

 

2017

[1]  Li QG#, He YH#, Wu H#, Yang CP, Pu SY, Fan SQ, Jiang LP, Shen QS, Wang XX, Chen XQ, Yu Q, Li Y, Sun C, Wang XT, Zhou JM, Li HP, Chen YB*, Kong QP*. A normalization-free and nonparametric method sharpens pan-cancer expression analysis. Theranostics. 2017; 7(11):2888-2899.

 

2016

[1]  He YH#, Chen XQ#, Yan DJ, Xiao FH, Lin R, Liao XP, Liu YW, Pu SY, Yu Q, Sun HP, Jiang JJ, Cai WW*, Kong QP*. Familial longevity study reveals a significant association of mitochondrial DNA copy number between centenarians and their offspring. Neurobiology of Aging. 2016; 47:218.e11-218.e18.

[2]  He YH#, Lu X#, Tian JY, DJ Yan, Li YC, Lin R, Perry B, Chen XQ, Yu Q, Cai WW*, Kong QP*. Mitochondrial DNA contributes equally to female and male longevity in Chinese centenarians. Experimental Gerontology. 2016; 83:94-96.

[3]  Xiao FH, Kong QP, Perry B, He YH*. Progress on the role of DNA methylation in aging and longevity. Briefings in Functional Genomics. 2016; 15(6):454-459.

[4] Han LY, Liu YF, Duan SW, Perry B, Li W*, He YH*. DNA methylation and hypertension: emerging evidence and challenges. Briefings in Functional Genomics. 2016; 15(6):460-469.

[5]  Jiang JJ, Cheng LH, Wu H, He YH*, Kong QP*. Insights into long noncoding RNAs of naked mole rat (Heterocephalus glaber) and their potential association with cancer resistance. Epigenetics & Chromatin. 2016; 9:51.

 

2015

[1]  He YH, Chen XQ, Yan DJ, Xiao FH, Liu YW, Lin R, Liao XP, Cai WW*, Kong QP*. Thyroid function decreases with age and may contribute to longevity in Chinese centenarians’ families. J Am Geriatr Soc. 2015; 63(7):1474-1476.

 

2014

[1]  He YH, Lu X, Wu H, Cai WW*, Yang LQ, Sun HP, Kong QP*. MtDNA content contributes to healthy aging in Chinese: a study from nonagenarians and centenarians. Neurobiology of Aging. 2014; 35(7):1779.e1-1779.e14.

 

[2]  He YH, Zhang YX, Yang LQ, Liao XP, Cai WW*, Kong QP*. Assessment of the health status of centenarians in the South of China: A cross-sectional study. J Am Geriatr Soc. 2014; 62(7):1402-1404.

[3]  He YH, Lu X, Yang LQ, Xu LY, Kong QP*. Association of the insulin-like growth factor binding protein 3 (IGFBP-3) polymorphism with longevity in Chinese nonagenarians and centenarians. Aging-US. 2014; 6(11):944-56.

 

2013

[1]  He YH, Li Y, Zhang SC, Perry B, Zhao TT, Wang YW*, Sun CH*. Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes. Biochemical and Biophysical Research Communications. 2013; 436:169-174.

[2]  He YH, Perry B, Bi MX, Sun H, Zhao TT, Li Y*, Sun CH*. Allosteric regulation of the calcium-sensing receptor in obese individuals. International Journal of Molecular Medicine. 2013; 32:511-518.

[3]  He YH, Li Y, Zhao TT, Wang YW*, Sun CH*. Ursolic acid inhibits adipogenesis in 3T3-L1 adipocytes through LKB1/AMPK pathway. PLoS One. 2013; 8: 8(7):e70135.

 

2012

[1]  He YH, Li ST, Wang YY, Wang G, He Y, Liao XL, Sun CH*, Li Y*. Postweaning low-calcium diet promotes later-life obesity induced by a high-fat diet. Journal of Nutritional Biochemistry. 2012; 23:1238-1244.

 

2011

[1]  He YH, Song Y, Liao XL, Wang L, Li G, Alima, Li Y*, Sun CH*. The calcium-sensing receptor affects fat accumulation via effects on antilipolytic pathways in adipose tissue of rats fed low-calcium diets. Journal of Nutrition. 2011; 141(11):1938-46.

[2]  He YH, Li ST, Wang YY, Wang G, He Y, Liao XL, Sun CH*, Li Y*. Postweaning low-calcium diet promotes later-life obesity induced by a high-fat diet. Journal of Nutritional Biochemistry. 2011; 23:1238-1244.

 

 

知识产权

[1] Zheng GR, Zhou DH, Zhang X, Khan S, He YH, Zhang PY. BCL-2 proteins degraders for cancer treatment. WO/2019/1441172019. 2019.

[2]  Zhou DH, He YH, Zheng GR, Zhang X. USP7 inhibitor as potential senolytic agent and its applications. 052592-590174. 2018.

[3]  Zhou DH, Zheng GR, He YH, Pi LY. Methods of treating diseases associated with senescent cell accumulation. WO2023064326A1. 2023.

[4]  何永捍,张翾,董婵娟,胡丽,王哲,何胜源. 一种靶向衰老细胞的近红外生物探针及其制备方法与用途. 202211569064.4. 2023.

  研究团队

工作人员

字美婷 科研秘书

潘永涨 研究实习员

张阳焕 研究实习员

在读研究生

胡丽      2022级博士研究生

张奥      2023级硕士研究生

周朕      2022级硕士研究生

袁胜杰  2022级硕士研究生

P. Nadeeshika Samarawickrama 2022级硕士研究生

Naheemat Modupeola GOLD     2022级硕士研究生

郑润滋  2021级硕士研究生(昆明理工大学联合培养)

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