科学研究 |
丁胜, PhD

丁胜

长聘教授，博士生导师

丁胜博士目前受聘于白菜网注册领取体验，担任首任白菜网注册领取体验经理、拜耳特聘教授。他于1999年在加州理工学院获得化学学士学位，并于2003年在斯克里普斯研究所获得化学博士学位。2003年至2011年间先后在斯克里普斯研究所化学系任职助理教授，副教授；2011年任职于美国加利福尼亚大学旧金山分校药物化学系，在格拉德斯通研究所担任冠名资深研究员及教授。丁胜教授是开发和应用全新化学手段研究干细胞和再生医学的引领者，一直致力于发现和鉴定可以调控细胞命运和功能（例如，不同发育阶段及不同组织中干细胞的维持、激活、分化和重编程）的小分子化合物。截止目前，丁胜教授已经发表了100多篇科研论文，研究综述和书籍章节，并在干细胞领域作出多项重要贡献。此外，丁胜教授还作为共同创始人，参与创建了多家生物技术公司。

研究方向

丁胜教授实验室一直致力于开发全新的化学方法，并将其用于干细胞与再生医学的研究，以期发现和鉴定可以调控细胞命运和功能（例如，不同发育阶段及不同组织中干细胞的维持、激活、分化和重编程）的全新小分子化合物。具体研究内容包括：（1）揭示干细胞自我更新和多能性的机理；（2）诱导胚胎干细胞向不同谱系（例如，神经、心脏、胰腺等）的分化；（3）人组织特异性干细胞和祖细胞的定向分化；（4）研究细胞的可塑性和重编成过程（例如，生成iPS细胞、转分化等）；（5）扩增无分裂能力的成体细胞（例如，心肌细胞、胰腺细胞等）；（6）解析参与胚胎发育的信号通路（例如，Wnt、Hh、BMP、FGF等）以及表观遗传学（组蛋白和DNA的甲基化与去甲基化）的分子机制；（7）开发药物发现的新技术。此外，丁胜教授研究团队还会针对所发现的小分子化合物开展大量的工作，通过全面的构效关系分析、亲和层析鉴定靶标、转录组学分析、蛋白质组学分析、化学/遗传上位分析以及体外、体内生化和功能分析，对其分子机制进行研究。到目前为止，很多功能小分子化合物及其作用机制已经或正在被确定，它们能够通过上述生物学过程之一对干/祖细胞进行调节。这些研究将最终推动干细胞的治疗性应用，以及帮助开发能够用于体内组织、器官再生或癌症治疗的小分子药物。

科学贡献

丁胜教授实验室以开发和应用全新的化学手段，解决在干细胞和再生医学研究中所面临的各种挑战闻名于世。通过不断开发新的方法（例如，筛选技术或生物建模），丁胜教授研究团队发现和鉴定了一系列能够在体外和体内调控多种细胞命运（例如，干细胞的维持，分化和重编程）的全新的小分子化合物。其中，很多小分子化合物能够在体外和体内调控特异性的细胞行为和表型，而这种变化在其他条件下极难或根本无法实现。另外，这些研究还发现了调控干细胞的新概念和新机制。目前开展的小分子化合物诱导细胞重编程的研究，旨在体外和体内实现将一种类型的细胞转变为同一组织或不同胚层的另一种细胞，将是细胞命运调控领域的一次巨大突破。这一研究将最终推动再生医学药物的出现，能够在疾病或损伤后，通过唤醒和指导体内自身细胞，对组织和器官开展原位修复及再生。此外，这些研究成果已经被用于多家生物技术公司的创立，并推动了学术和生物制药界开发基于小分子化合物的再生医学疗法，用于人类疾病的治疗。

研究成果

1、发现了一系列小分子化合物，能够在诱导多能干细胞（iPS细胞）产生的过程中，取代外源转录因子和显著提高重编程的效率/速度。通过研究这些小分子化合物，揭示了重编程过程的新机制。
2、开发了一种全新的细胞转分化技术（即谱系特异性重编程），在包含小分子化合物的特定条件下，可以把成纤维细胞转变为能够扩增的心脏、神经、血管内皮、胰腺和肝脏细胞。
3、发现并从机制上鉴定了多个全新的小分子化合物，可以用于替换维持胚胎干细胞自我更新的生长因子，促进胚胎干细胞的生存，或者诱导胚胎干细胞向神经、心脏和定形内胚层谱系的分化。

荣誉和奖励

2012          “40 Under 40 Emerging Leaders”, San Francisco Business Times    
2011          William K. Bowes Jr. Distinguished Investigator, The Gladstone Institutes    
2010          NIH Transformative Research Award    
2010          Named as one of the 100 most inspiring people in the life sciences industry by PharmaVoice    
2009          #1 of Top 10 Innovations, and Top 5 People in 2009 by The Scientist Magazine    
2008          Prostate Cancer Foundation Challenge Award    
2008          New Faculty Award from California Institute for Regenerative Medicine    
2000          Fellowship in Biological Science, Howard Hughes Medical Institute.    
1999          Richard P. Schuster Memorial Prize, Caltech    
1998          Carnation Merit Award, Caltech    
1997          Rosalind W. Alott Merit Award, Caltech    
1997          National Merit Scholar, Phi Tau Phi Honor Association.    
1997          Member of Tau Beta Pai, the National Engineering Honor Society.

代表性论文

1. Zhang M, Lin YH, Sun YJ, Zhu S, Zheng J, Liu K, Cao N, Li K, Huang Y, Ding S. Pharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation.     Cell Stem Cell. 2016 May 5;18(5):653-67.    
2. Cao N, Huang Y, Zheng J, Spencer CI, Zhang Y, Fu JD, Nie B, Xie M, Zhang M, Wang H, Ma T, Xu T, Shi G, Srivastava D, Ding S. Conversion of human fibroblasts into functional cardiomyocytes by small molecules.     Science. 2016 Apr 28.[Epub ahead of print]    
3. Zhang Y, Cao N, Huang Y, Spencer CI, Fu JD, Yu C, Liu K, Nie B, Xu T, Li K, Xu S, Bruneau BG, Srivastava D, Ding S. Expandable Cardiovascular Progenitor Cells Reprogrammed from Fibroblasts.     Cell Stem Cell. 2016 Mar 3;18(3):368-81.
4. Zhu S, Russ HA, Wang X, Zhang M, Ma T, Xu T, Tang S, Hebrok M, Ding S. Human pancreatic beta-like cells converted from fibroblasts.     Nat Commun. 2016 Jan 6;7:10080.
5. Ma T, Li J, Xu Y, Yu C, Xu T, Wang H, Liu K, Cao N, Nie BM, Zhu SY, Xu S, Li K, Wei WG, Wu Y, Guan KL, Ding S. Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming.     Nat Cell Biol. 2015 Nov;17(11):1379-87.
6. Tang S, Xie M, Cao N, Ding S. Patient-Specific Induced Pluripotent Stem Cells for Disease Modeling and Phenotypic Drug Discovery.     J Med Chem. 2016 Jan 14;59(1):2-15..
7. Zhu S, Wang H, Ding S.Reprogramming fibroblasts toward cardiomyocytes, neural stem cells and hepatocytes by cell activation and signaling-directed lineage conversion.     Nature Protocol 10(7):959-73, 2015.
8. Nie T, Hui X, Gao X, Nie B, Mao L, Tang X, Yuan R, Li K, Li P, Xu A, Liu P, Ding S, Han W, Cooper GJ, Wu D. Conversion of non-adipogenic fibroblasts into adipocytes by a defined hormone mixture.     Biochem J. 467(3):487-94, 2015.
9. Yu C, Liu Y, Ma T, Liu K, Xu S, Zhang Y, Liu H, La Russa M, Xie M, Ding S, Qi LS. Small molecules enhance CRISPR genome editing in pluripotent stem cells.     Cell Stem Cell 16, 142-7, (2015).
10. Yu C, Liu K, Tang S, Ding S. Chemical approaches to cell reprogramming.     Curr Opin Genet Dev. 28:50-6, (2014).
11. Ding S. Deciphering therapeutic reprogramming.     Nature Medicine 20, 816-817, (2014).
12. Jin C, Yang L, Xie M, Lin C, Merkurjev D, Yang JC, Tanasa B, Oh S, Zhang J, Ohgi K, Zhou H, Li W, Evans CP, Ding S & Rosenfeld MG. Chem-seq permits identification of genomic targets of drugs against androgen receptor regulation selected by functional phenotypic screens.     Proc Natl Acad Sci USA 111, 9235-9240, (2014).
13. Zhu S, Rezvani M, Harbell J, Mattis AN, Wolfe AR, Benet LZ, Willenbring H & Ding S. Mouse liver repopulation with hepatocytes generated from human fibroblasts.     Nature 508, 93-97, (2014).
14. Li K, Zhu S, Russ HA, Xu S, Tao X, Zhang Y, Ma T, Hebrok M and Ding S. Small Molecules Facilitate the Reprogramming of Mouse Fibroblasts into Pancreatic Lineages.     Cell Stem Cell 14, 228-36, (2014).
15. Wang H, Cao N, Spencer CI, Nie B, Ma T, Xu T, Zhang Y, Wang X, Srivastava D, Ding S. Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, Oct4.     Cell Report 6(5):951-60, (2014).
16. Xie M, Cao N, Ding S. Small molecules for cell reprogramming and heart repair: progress and perspective.     ACS Chem Biol. 9(1):34-44, (2014).
17. Zhu S, Ambasudhan R, Sun W, Kim HJ, Talantova M, Wang X, Zhang M, Zhang Y, Laurent T, Parker J, Kim HS, Zaremba JD, Saleem S, Sanz-Blasco S, Masliah E, McKercher SR, Cho YS, Lipton SA, Kim J, Ding S. Small molecules enable OCT4-mediated direct reprogramming into expandable human neural stem cells.     Cell Res. 24(1):126-9, (2014).
18. Zhao JJ, Ouyang H, Luo J, Patel S, Xue Y, Quach J, Sfeir N, Zhang M, Fu X, Ding S, Chen S, Zhang K. Induction of Retinal Progenitors and Neurons from Mammalian Muller Glia under Defined Conditions     . J Biol Chem. 289(17):11945-51, (2014).
19. Fu JD, Stone NR, Liu L, Spencer CI, Qian L, Hayashi Y, Delgado-Olguin P, Ding S, Bruneau BG, Srivastava D. Direct Reprogramming of Human Fibroblasts toward a Cardiomyocyte-like State.     Stem Cell Reports 1(3):235-47, (2013).
20. Calvanese V, Chavez L, Laurent T, Ding S, Verdin E. Dual-color HIV reporters trace a population of latently infected cells and enable their purification.     Virology 446(1-2):283-92, (2013).
21. Lu B, Morgans CW, Girman S, Luo J, Zhao J, Du H, Lim S, Ding S, Svendsen C, Zhang K, Wang S. Neural Stem Cells Derived by Small Molecules Preserve Vision.     Transl Vis Sci Technol. 2(1):1, (2013).
22. Li W, Ding S. Converting mouse epiblast stem cells into mouse embryonic stem cells by using small molecules.     Methods Mol Biol. 1074:31-7, (2013).
23. Li W, Li K, Wei W, Ding S. Chemical Approaches to Stem Cell Biology and Therapeutics.     Cell Stem Cell 13, 270-283, (2013).
24. Li W, Ding S. Converting mouse epiblast stem cells into mouse embryonic stem cells by using small molecules.     Methods Mol Biol. 1074:31-7, (2013).
25. Lin C, Yu C, Ding S. Toward directed reprogramming through exogenous factors.     Curr Opin Genet Dev. 23(5):519-25, (2013).
26. Xu T, Zhang M, Laurent T, Xie M, Ding S. chemical approaches for modulating lineage-specific stem cells and progenitors.     Stem Cells Transl Med. 2(5):355-61, (2013).
27. Wang F, Scoville D, He XC, Mahe M, Box A, Perry J, Smith NR, Lei Nanye N, Davies PS, Fuller MK, Haug JS, McClain M, Gracz AD, Ding S, Stelzner M, Dunn JC, Magness ST, Wong MH, Martin M, Helmrath M, Li L. Isolation and Characterization of Intestinal Stem Cells Based on Surface Marker Combinations and Colony-Formation Assay.     Gastroenterology 145(2):383-95.e1-21, (2013).
28. Li J, Huang NF, Zou J, Laurent TJ, Lee JC, Okogbaa J, Cooke JP, Ding S. Conversion of Human Fibroblasts to Functional Endothelial Cells by Defined Factors.     Arterioscler Thromb Vasc Biol. 33(6):1366-75, (2013).
29. Li W, Jiang K, Wei W, Shi Y, Ding S. Chemical approaches to studying stem cell biology.     Cell Res. 23 (1):81-91, (2013).
30. Zhao J, Sun W, Cho HM, Ouyang H, Li W, Lin Y, Do J, Zhang L, Ding S, Liu Y, Lu P, Zhang K. Integration and long distance axonal regeneration in the central nervous system from transplanted primitive neural stem cells.     J Biol Chem. 288(1):164-8, (2013).
31. Ma T, Xie M, Laurent T, Ding S. Progress in the reprogramming of somatic cells.     Circulation Research 112(3):562-74, (2013).
32. Zhang Y, Li W, Laurent T, Ding S. Small molecules, big roles -- the chemical manipulation of stem cell fate and somatic cell reprogramming.     J Cell Sci. 125, 5609-20, (2012).
33. Kim J, Ambasudhan R, Ding S. Direct lineage reprogramming to neural cells.     Current Opinion in Neurobiology 22(5):778-84, (2012).
34. Nie B, Wang H, Laurent T, Ding S. Cellular reprogramming: a small molecule perspective.     Curr Opin Cell Biol. 24(6):784-92, (2012).
35. Westenskow PD, Moreno SK, Krohne TU, Kurihara T, Zhu S, Zhang ZN, Zhao T, Xu Y, Ding S, Friedlander M. Using flow cytometry to compare the dynamics of photoreceptor outer segment phagocytosis in iPS-derived RPE cells.     Invest Ophthalmol Vis Sci. 14;53(10):6282-90, (2012).
36. Liu K, Ding S. Target practice: modeling tumors with stem cells.     Cell 149, 1185-1187, (2012).
37. Li H, Zhou H, Wang D, Qiu J, Zhou Y, Li X, Rosenfeld MG, Ding S, Fu XD. Versatile pathway-centric approach based on high-throughput sequencing to anticancer drug discovery.     Proc Natl Acad Sci U S A 109(12):4609-14, (2012).
38. Li W, Jiang K, Ding S. A chemical approach to control cell fate and function.     Stem Cells 30(1):61-8, (2012).
39. Ukrohne TU, Westenskow PD, Kurihara T, Friedlander DF, Lehmann M, Dorsey AL, Li W, Zhu S, Schultz A, Wang J, Siuzdak G, Ding S, Friedlander M. Generation of retinal pigment epithelial cells from small molecules and OCT4 reprogrammed human induced pluripotent stem cells.     Stem Cells Transl Med. 1(2):96-109, (2012).
40. Krohne TU, Westenskow PD, Kurihara T, Friedlander DF, Lehmann M, Dorsey AL, Li W, Zhu S, Schultz A, Wang J, Siuzdak G, Ding S. Friedlander M. Generation of retinal pigment epithelial cells from small molecules and OCT4-reprogrammed human induced pluripotent stem cells.     Paediatr Int Child Health 1(2):96-109, (2012).
41. Efe JA, Hilcove S, Kim J, Zhou H, Ouyang K, Wang G, Chen J, Ding S. Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy.     Nature Cell Biology 13, 215–222, (2011).
42. Ambasudhan R, Talantova M, Coleman R, Yuan X, Zhu S, Lipton SA, Ding S. Direct Reprogramming of Adult Human Fibroblasts to Functional Neurons under Defined Conditions.     Cell Stem Cell 9, 113-118, (2011).
43. Zhang K. and Ding S. Stem Cells and Eye Development,     N Engl J Med 365:370 – 372, (2011).
44. Li W, Ding S. Human pluripotent stem cells: decoding the naïve state.     Sci Transl Med. 3(76):76ps10. (2011).
45. Zhu S, Wei W, Ding S. Chemical Strategies for Stem Cell Biology and Regenerative Medicine.     Annu Rev Biomed Eng. 13:73–90, (2011).
46. Li W, Sun W, Zhang Y, Wei W, Ambasudhan R, Xia P, Talantova M, Lin T, Kim J, Wang X, Kim WR, Lipton SA, Zhang K, Ding S. Rapid induction and long-term self-renewal of primitive neural precursors from human embryonic stem cells by small molecule inhibitors.     Proc. Natl. Acad. Sci. USA 108 (20) 8299-8304, (2011).
47. Yuan X, Wan H, Zhao X, Zhu S, Zhou Q, Ding S, Combined Chemical Treatment Enables Oct4-Induced Reprogramming from Mouse Embryonic Fibroblasts.     Stem Cells 29(3), 549-53, (2011).
48. Kim J, Efe JA, Zhu S, Talantova M, Yuan X, Wang S, Lipton SA, Zhang K, Ding S. Direct reprogramming of mouse fibroblasts to neural progenitors.     Proc. Natl. Acad. Sci. USA 108 (19) 7838-7843, (2011).
49. Li Y, Prasad A, Jia Y, Roy SG, Loison F, Mondal S, Kocjan P, Silberstein LE, Ding S, Luo HR. Pretreatment with phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitor SF1670 augments the efficacy of granulocyte transfusion in a clinically relevant mouse model.     Blood 117(24):6702-13, (2011).
50. P Perry JM, He XC, Sugimura R, Grindley JC, Haug JS, Ding S, Li L. Cooperation between both Wnt/β-catenin and PTEN/PI3K/Akt signaling promotes primitive hematopoietic stem cell self-renewal and expansion.     Genes Dev. 25, 1928-42, (2011).
51. Zhu S, Ma T, Li J, Ding S. Recent advances in chemically induced reprogramming.     Cell Cycle 10(6):871-2 (2011).
52. Xu T, Wang X, Zhong B, Nurieva RI, Ding S, Dong C. Ursolic Acid Suppresses Interleukin-17 (IL-17) Production by Selectively Antagonizing the Function of ROR{gamma}t Protein.     J Biol Chem. 286(26):22707-10, (2011).
53. Efe JA, Ding S. Reprogramming, transdifferentiation and the shifting landscape of cellular identity.     Cell Cycle 10(12):1886-7, (2011).
54. Shen Y, Shi C, Wei W, Yu W, Li W, Yang Y, Xu J, Ying W, Sui X, Fang L, Lin W, Yang H, Ding S, Shen H, Shi Y, Deng H. The heterogeneity and dynamic equilibrium of rat embryonic stem cells.     Cell Res. 21(7):1143-7, (2011).
55. Efe JA, Ding S. The evolving biology of small molecules: controlling cell fate and identity.     Philos Trans R Soc Lond B Biol Sci. 366(1575):2208-21, (2011).
56. Wang Q, Xu X, Li J, Liu J, Gu H, Zhang R, Chen J, Kuang Y, Fei J, Jiang C, Wang P, Pei D, Ding S, Xie X. Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells.     Cell Res. 21(10):1424-35, (2011).
57. Liu J, Johnson K, Li J, Piamonte V, Steffy BM, Hsieh MH, Ng N, Zhang J, Walker JR, Ding S, Muneoka K, Wu X, Glynne R, Schultz PG. Regenerative phenotype in mice with a point mutation in transforming growth factor beta type I receptor (TGFBR1).     Proc. Natl. Acad. Sci. USA 108(35):14560-5, (2011).
58. Efe JA, Yuan X, Jiang K, Ding S. Development unchained: how cellular reprogramming is redefining our view of cell fate and identity.     Sci Prog. 94, 298-322, (2011).
59. Ko SH, Nauta A, Morrison SD, Zhou H, Zimmermann A, Gurtner GC, Ding S, Longaker MT. Antimycotic ciclopirox olamine in the diabetic environment promotes angiogenesis and enhances wound healing.     PLoS One 6(11):e27844, (2011).
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