师资

饶枫
副教授(研究员)
0755-88018439
raof@sustech.edu.cn

饶枫博士是南方科技大学生命科学学院生物系副教授,研究员。新加坡国立大学生物医学学士,南洋理工大学生物学博士,美国约翰-霍普金斯大学医学院博士后,加入南科大前任职北京生命科学研究所研究员。饶枫实验室(信使与代谢生物学实验室)主要研究细胞内新兴小分子信使的功能机制和蛋白质稳态的代谢调控, 以及疾病微环境中这些生命过程如何参与神经与代谢和肿瘤组织的互调互作,获基金委优秀青年科学基金,重大研究计划和国自然面上与深圳市孔雀团队等项目支持。作为最后通讯作者在Nature Metabolism, PNAS (x2), 和Nature Communications等杂志上发表研究论文多篇。成果多次被作为研究亮点点评或被F1000等推荐。担任中国病理生理协会蛋白质修饰和疾病专委会秘书,中国神经科学学会离子通道与受体分会委员, Genome Instability & Disease 杂志编委。


研究领域

一、焦磷酸肌醇(IP7)代谢小分子在功能机制研究 。

       G蛋白偶联受体(GPCR)信号转导通路的新型第二信使三磷酸肌醇(IP3)能被一系列的肌醇激酶进一步磷酸化生成多种多磷酸肌醇(IP4-8),其功能了解不多。其中,能量高,不稳定的焦磷酸肌醇(IP7/8)的作用原理尤为难解。我们之前发现IP7是肿瘤细胞里调控凋亡和转移的命运抉择开关,在早期通过促凋亡来抑制肿瘤发生,后期则通过诱导上皮细胞-间充质转换来促进肿瘤恶化与转移(Rao et al. Mol Cell, 2014;Rao et al. PNAS, 2015)。但是,IP7在疾病微环境中所感应的上游信号不清楚。通过研究焦磷酸肌醇特异的合成和水解酶的催化及调控机制,我们着眼于在细胞和小鼠模型里发掘焦磷酸肌醇介导的生理过程(如代谢稳态和肿瘤转移),并揭示相关的信号转导通路。在此基础上,我们通过化学生物学和生物化学的方法寻找小分子的直接作用位点和作用模式,希望能够归纳出焦磷酸肌醇作用的普遍规律。基于焦磷酸肌醇在癌症等疾病发生过程中的作用,我们的机制和功能研究或可为治疗相关疾病提供新靶点

二、CRL泛素连接酶的拟素化修饰的代谢调控与疾病。

       Cullin-RING ligase(CRL)家族泛素连接酶介导了总泛素化的20%,在癌症和糖尿病等多种疾病中失调,是新兴治疗靶点。CRL 还是最近兴起的蛋白降解靶向联合体(PROTAC)小分子药物所倚仗的泛素连接酶。CRL被拟素化修饰激活,受去拟泛素化酶CSN 抑制。我们研究CRL拟素化的代谢分子调控路径,包括多磷酸肌醇小分子和营养 (Rao et al. PNAS, 2014; Scherer,…, Rao*. PNAS, 2016; Lin,…, Rao*. PNAS, 2020)。相关发现或可为研发靶向CRL的新路径和解决PROTAC耐药提供理论基础。

 

工作经历
2016-至今 南方科技大学生物系,副教授
2015-2016 北京生命科学研究所,研究员
2011-2015 美国约翰霍普金斯大学医学院,博士后
2006-2007 新加坡南洋理工大学,项目主任
2005-2006 新加坡国立大学,科研助理

 

学习经历
2007-2011 新加坡南洋理工大学生物学博士
2001-2005 新加坡国立大学生物医学学士

 

招聘信息
职位招聘:本实验室现招聘科研助理,博士后和研究生。有意者请发邮件至raof@sustech.edu.cn

 

代表文章

1. Zhang X#, Li N#, Zhang J#, Zhang Y#, Yang X#, Luo Y, Zhang B, Xu Z, Zhu Z, Yang X, Yan Y, Lin B, Wang S, Chen D, Ye C, Ding Y, Lou M, Wu Q, Hou Z, Zhang K, Liang Z, Wei A, Wang B, Wang C, Jiang N, Zhang W, Xiao G, Ma C, Ren Y, Qi X, Han W, Wang C*, Rao F.*. 5-IP7 is a GPCR messenger mediating neural control of synaptotagmin-dependent exocytosis and glucose homeostasis. Nat. Metab. 2021 3, 1400-1414. https://www.nature.com/articles/s42255-021-00468-7

2. Lin H#, Yan Y#, Luo Y#, So WY#, Wei X, Zhang X, Yang X, Zhang J, Su Y, Yang X, Zhang B, Zhang KJ, Jiang N, Chow BKC, Han W, Wang F, and Rao F*. IP6-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion. Nat. Commun. 2021 12, 2461. https://doi.org/10.1038/s41467-021-22941-3

3. Zhang X, Shi S, Su Y, Yang X, He S, Wu J, Zhang J, Rao, F.*. Suramin and NF449 are IP5K inhibitors that disrupt IP6-mediated regulation of cullin RING ligase and sensitize cancer cells to MLN4924/Pevonedistat. J. Biol. Chem. 2020 295,10281-10292.

4. Lin H. #, Zhang XZ. #, Liu L., Fu QY., Zang CL., Ding Y., Xu ZX., He SN., Yang XL., Wei XY., Mao HB., Cui YS, Wei Yi., Zhou CZ., Du LL., Huang N., Zheng N., Wang T., and Rao F.*. Molecular basis of metabolite-dependent Cullin RING ligase deneddylation by the COP9 Siganalosome. Proc Natl Acad Sci USA. 2020, DOI: 10.1073/pnas.1911998117.

5. Rao F.*, Lin H., Su Y.. Cullin RING ligase regulation by the COP9 Signalosome: Structural Mechanisms and New Physiologic Players. Adv. Exp. Med. Biol. 2020, 1217, 47-60. (Invited Chapter of the book “Cullin RING Ligases and Neddylation”)

6. Zhang XZ., Rao F.*. Are inositol polyphosphates the missing link in dynamic Cullin RING ligase regulation by the COP9 Signalosome? Biomolecules. Special Issue on “ZOMES”: 2019, 9, 349.

7. 魏文毅*、孙毅*、曹诚、常智杰、陈策实、陈佺、程金科、冯仁田、高大明、胡荣贵、贾立军、姜天霞、金建平、李汇华、李卫、刘翠华、饶枫、商瑜、宋质银、万勇、王平、王占新、吴缅、吴乔、谢旗、谢松波、谢志平、徐平、许执恒、杨波、阳成伟、应美丹、张宏冰、张令强、赵永超、周军、朱军、王琳芳、张宏、王琛、邱小波*. 类泛素蛋白及其中文命名(Ubiquitin-like Proteins and their Chinese Nomenclatures).  科学通报. 2018, 63(25):2564-2569.

8. Fu C., Tyagi R., Chin AC., Rojas T., Li RJ., Guha P., Bernstein IA., Rao F., Xu R., Cha JY., Xu J., Snowman AM., Semenza GL., Snyder SH.*. Inositol Polyphosphate Multikinase Inhibits Angiogenesis via Inositol Pentakisphosphate-Induced HIF-1α [J]. Circulation Research. 2018 Feb 2, 122(3):457-472.

9. Scherer PC., Zaccor NW., Neumann NM., Vasavda C., Barrow R., Ewald AJ., Rao F., Sumner CJ., Snyder SH.*. TRPV1 is a physiological regulator of μ-opioid receptors[J]. Proc Natl Acad Sci USA. 2017 Dec 19, 114(51):13561-13566.

10. Scherer PC.#, Ding Y.#, Liu Z., Xu J., Mao H., Barrow JC., Wei N., Zheng N., Snyder SH*, Rao F.*. Inositol hexakisphosphate(IP6) generated by IP5K mediates cullin-COP9 signalosome interactions and CRL function. Proc Natl Acad Sci USA2016, 113, 3503-8.

11. Rao F.#Xu J.#, Fu C., Cha JY., Xu R., Gadalla MM., Wu M., Fiedler D., Barrow JC., Snyder SH.*. Inositol pyrophosphates promote cancer growth and metastasis by antagonizing the tumor suppressor LKB1. Proc Natl Acad Sci USA. 2015 112, 1773-8.

12. Rao F.#Xu J.#, Kahn AB., Cha J., Xu R. Tyagi R., Dang Y., Chakraborty A., Snyder SH.*. Inositol hexakisphosphate kinase-1 mediates assembly/ disassembly of the CRL4-Signalosome complex to regulate DNA repair and cell death. Proc Natl Acad Sci USA. 2014, 111, 16005-16010.

13. Rao F., Cha J., Xu J., Xu R., Vandiver MS., Tokhunt RT., Wu M., Fiedler D., Barrow J., Snyder SH.*. Inositol pyrophosphates mediate the DNA-PK/ATM-p53 cell death pathway by regulating CK2 phosphorylation of Tti1/Tel2. Mol Cell. 2014, 54, 119-32.

14. Tan E.#Rao F.#, Pasunooti S., Pham TH., Soehano I., Turner MS., Liew CW., Lescar J., Pervushin K., Liang Z-X*.  Solution structure of the PAS domain of a thermophilic YybT homolog reveals a potential ligand-binding site. J Biol Chem. 2013, 288:11949-59.

15. Xu R., Sen N., Paul BD., Rao F., Vandiver MS., Snyder SH.*. Inositol phosphate multikinase catalyzes the acetylation of p53 by p300, thereby functioning as a p53 transcriptional co-activator. Science Signaling. 2013, 6, ra22: 1-10.

16. Vandiver MS., Paul BD., Xu R., Karuppagounder S., Rao F., Snowman AM., Ko HS., Li YI., Sen N., Dawson VL., Dawson TM., Snyder SH.*. Sulfhydration mediates neuroprotective actions of Parkin. Nat Commun. 2013, 4:1626.

17. Xu R, Paul BD, Smith DR, Tyagi R, Rao F., Khan AB., Blech DJ., Vandiver MS., Harraz MM., Guha P., Ahmed I., Sen N., Gallagher M., Snyder SH.*. Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction. Proc Natl Acad Sci USA. 2013, 6, 110, 16181-.

18. Cha J., Xu J., Paul BD., Rao F., Ho G., Snyder SH.*. Dexras1 Mediates adipogenesis and diet-induced obesity. Proc Natl Acad Sci USA. 2013, 110, 20575-.

19. Chia WS., Chia, XD., Rao F., Bar-Nun S., Geifman S.*. ATP binding to p97/VCP regulates selective recruitment of adaptors to its proximal N-domain. PLOS ONE. 2012, 7: e50490.

20. Chen M.W., Kotaka M., Vonrhein C., Bricogne G., Rao F., Chuah M.L., Svergun D., Schneider G., Liang Z-X.*. and Lescar J. *. Structural insights into the regulatory mechanism of the response regulator RocR from Pseudomonas aeruginosa in cyclic di-GMP signaling. J Bacteriol. 2012, 194:4837-4846.

21. Rao, F., Wang T., Li M., Li Z., Hong N., Zhao H., Yan Y., Lu W., Chen T., Wang W., Lim M., Yuan Y., Liu L., Zeng L., Wei Q., Guan G., Li C., Hong Y.*. Medaka tertproduces multiple variants with differential expression during differentiation in vitro and in vivo Biol. Sci2011, 7(4):426-439.

22. Rao, F., Ji, Q., Soehano I., Liang Z-X.*. Unusual Heme-Binding PAS Domain from YybT Family Proteins. J Bacteriol. 2011, 193:1543-1551.

23. Murugan E., Kong R., Sun H., Rao F., Liang, Z-X. Expression, purification and characterization of acyl carrier protein phosphodiesterase from Pseudomonas aeruginosaProtein Expres. Purif. 2010, 71:132-138.

24. Rao, F.,See, RY., Zhang, D., Toh, DC., Liang Z-X*. YybT is a signaling protein that contains a cyclic-di-nucleotide phosphodiesterase domain and a GGDEF domain with ATPase activity. J Biol Chem. 2010, 285:473-82.

25. Rao, F.*, Qi, Y., Murugan, E., Pasunooti, S., Ji, Q.. 2’,3’-cAMP hydrolysis by metal-dependent phosphodiesterases containing DHH, EAL, and HD domains is non-specific: implications for PDE screening. Res. Commun.2010, 398:500-505.

26. Rao, F., Pasunooti S., Ng Y., Zhuo W., Lim L., Liu AW., Liang Z-X.*. Enzymatic synthesis of c-di-GMP using a thermophilic diguanylate cyclase. Anal Biochem. 2009, 389:138-42.

27. Rao F., Qi Y., Chong HS., Kotaka M., Li B., Lescar J., Tang K., Liang Z-X.*. The functional role of a conserved loop in EAL domain-based c-di-GMP specific phosphodiesterase. J Bacteriol. 2009, 191:4722-31.

28. Qi Y., Rao F., Luo Z., Liang Z- X.*. A flavin cofactor-binding PAS domain regulates C-di-GMP synthesis in AxDGC2 from Acetobacter xylinumBiochemistry. 2009, 48:10275-85.

29. Kotaka M.*., Dutta S., Lee H.C., Lim M., Wong Y., Rao F., Mitchell E.P., Liang Z-X, Lescar JX.*. Expression, purification and preliminary crystallographic analysis of Pseudomonas aeruginosaRocR protein. Acta Crystallogr. F. 2009, 65: 1035-1038.

30. Rao F., Yang Y., Qi Y., Liang Z-X*. Catalytic mechanism of C-di-GMP specific phosphodiesterase: a study of the EAL domain containing protein RocR from Psudomonas aeruginosa. J Bacteriol. 2008, 190:3622-31.

(*= Corresponding Author  ; #=Co-first Author  )

 

科研项目

序号项目来源与类别承担方式项目名称起止时间状态
1深圳市科创委-学科布局项目

主持

体内天然信号小分子参与肿瘤转移的机制和转化研究20170701--20200630在研
2深圳市科创委-自由探项目

主持

六磷酸肌醇(IP6)小分子调控胰岛素分泌和糖尿病发生的机制和转化研究20180309—20200331在研
3深圳市科创委-孔雀技术创新项目

主持

多磷酸肌醇激酶蛋白质机器的功能和转化研究20190320--20210319在研
4国家自然科学基金重大研究计划培育项目

主持

CRL泛素连接酶受拟素化修饰(Neddylation)动态调控的机制与功能研究20190101--20211231在研
5国家自然科学基金面上项目

主持

六磷酸肌醇-CRL-CSN复合物调控胰岛素分泌和糖尿病发生的功能与机制研究20190101--20221231在研
6广东省自由申请项目

主持

磷酸肌醇小分子调控蛋白类泛素化(neddylation)和胰岛素分泌的功能与机制研究20180501--20210430在研
7美国NIH Health Science Service参与Drug Abuse Research Center Distinguished Award Grant20110601--20160531结题
8Basci Research grant from Biomedical Research (BMRC) of singapore参与Structure and Function of Novel Antibiotic Targets in opportunistic Pathogen Pseudomonas Aeruginosa20070101--20100131结题
9Academic Research Council Grant Ministry of Education参与Function of Sensor-Coupled Diguanylate Cyclases in Opportunistic Pathogen P. Aeruginosa20061001-20081031结题

 

专利
1. Liang, Z-X., Rao, F. Diguanylate cyclase method of producing the same and its use in the manufacture of cyclic-di-GMP and analogues thereof. 2014, US Patent No: 8,859,237.