師資隊(duì)伍 |
丁勝, PhD

丁勝

長(zhǎng)聘教授，博士生導(dǎo)師

丁勝博士目前受聘于清華大學(xué)，擔(dān)任首任藥學(xué)院院長(zhǎng)、拜耳特聘教授。他于1999年在加州理工學(xué)院獲得化學(xué)學(xué)士學(xué)位，并于2003年在斯克里普斯研究所獲得化學(xué)博士學(xué)位。2003年至2011年間先后在斯克里普斯研究所化學(xué)系任職助理教授，副教授；2011年任職于美國(guó)加利福尼亞大學(xué)舊金山分校藥物化學(xué)系，在格拉德斯通研究所擔(dān)任冠名資深研究員及教授。丁勝教授是開(kāi)發(fā)和應(yīng)用全新化學(xué)手段研究干細(xì)胞和再生醫(yī)學(xué)的引領(lǐng)者，一直致力于發(fā)現(xiàn)和鑒定可以調(diào)控細(xì)胞命運(yùn)和功能（例如，不同發(fā)育階段及不同組織中干細(xì)胞的維持、激活、分化和重編程）的小分子化合物。截止目前，丁勝教授已經(jīng)發(fā)表了100多篇科研論文，研究綜述和書(shū)籍章節(jié)，并在干細(xì)胞領(lǐng)域作出多項(xiàng)重要貢獻(xiàn)。此外，丁勝教授還作為共同創(chuàng)始人，參與創(chuàng)建了多家生物技術(shù)公司。

研究方向

丁勝教授實(shí)驗(yàn)室一直致力于開(kāi)發(fā)全新的化學(xué)方法，并將其用于干細(xì)胞與再生醫(yī)學(xué)的研究，以及發(fā)現(xiàn)和鑒定可以調(diào)控細(xì)胞命運(yùn)和功能（例如，不同發(fā)育階段及不同組織中干細(xì)胞的維持、激活、分化和重編程）的全新小分子化合物。具體研究?jī)?nèi)容包括：（1）揭示干細(xì)胞自我更新和多能性的機(jī)理；（2）誘導(dǎo)胚胎干細(xì)胞向不同譜系（例如，神經(jīng)、心臟、胰腺等）的分化；（3）人組織特異性干細(xì)胞和祖細(xì)胞的定向分化；（4）研究細(xì)胞的可塑性和重編成過(guò)程（例如，生成iPS細(xì)胞、轉(zhuǎn)分化等）；（5）擴(kuò)增無(wú)分裂能力的成體細(xì)胞（例如，心肌細(xì)胞、胰腺?細(xì)胞等）；（6）解析參與胚胎發(fā)育的信號(hào)通路（例如，Wnt、Hh、BMP、FGF等）以及表觀(guān)遺傳學(xué)（組蛋白和DNA的甲基化與去甲基化）的分子機(jī)制；（7）開(kāi)發(fā)藥物發(fā)現(xiàn)的新技術(shù)。此外，丁勝教授研究團(tuán)隊(duì)還會(huì)針對(duì)所發(fā)現(xiàn)的小分子化合物開(kāi)展大量的工作，通過(guò)全面的構(gòu)效關(guān)系分析、親和層析鑒定靶標(biāo)、轉(zhuǎn)錄組學(xué)分析、蛋白質(zhì)組學(xué)分析、化學(xué)/遺傳上位分析以及體外、體內(nèi)生化和功能分析，對(duì)其分子機(jī)制進(jìn)行研究。到目前為止，很多功能小分子化合物及其作用機(jī)制已經(jīng)或正在被確定，它們能夠通過(guò)上述生物學(xué)過(guò)程之一對(duì)干/祖細(xì)胞進(jìn)行調(diào)節(jié)。這些研究將最終推動(dòng)干細(xì)胞的治療性應(yīng)用，以及幫助開(kāi)發(fā)能夠用于體內(nèi)組織、器官再生或癌癥治療的小分子藥物。

科學(xué)貢獻(xiàn)

丁勝教授實(shí)驗(yàn)室以開(kāi)發(fā)和應(yīng)用全新的化學(xué)手段，解決在干細(xì)胞和再生醫(yī)學(xué)研究中所面臨的各種挑戰(zhàn)聞名于世。通過(guò)不斷開(kāi)發(fā)新的方法（例如，篩選技術(shù)或生物建模），丁勝教授研究團(tuán)隊(duì)發(fā)現(xiàn)和鑒定了一系列能夠在體外和體內(nèi)調(diào)控多種細(xì)胞命運(yùn)（例如，干細(xì)胞的維持，分化和重編程）的全新的小分子化合物。其中，很多小分子化合物能夠在體外和體內(nèi)調(diào)控特異性的細(xì)胞行為和表型，而這種變化在其他條件下極難或根本無(wú)法實(shí)現(xiàn)。另外，這些研究還發(fā)現(xiàn)了調(diào)控干細(xì)胞的新概念和新機(jī)制。目前開(kāi)展的小分子化合物誘導(dǎo)細(xì)胞重編程的研究，旨在體外和體內(nèi)實(shí)現(xiàn)將一種類(lèi)型的細(xì)胞轉(zhuǎn)變?yōu)橥唤M織或不同胚層的另一種細(xì)胞，將是細(xì)胞命運(yùn)調(diào)控領(lǐng)域的一次巨大突破。這一研究將最終推動(dòng)再生醫(yī)學(xué)藥物的出現(xiàn)，能夠在疾病或損傷后，通過(guò)喚醒和指導(dǎo)體內(nèi)自身細(xì)胞，對(duì)組織和器官開(kāi)展原位修復(fù)及再生。此外，這些研究成果已經(jīng)被用于多家生物技術(shù)公司的創(chuàng)立，并推動(dòng)了學(xué)術(shù)和生物制藥界開(kāi)發(fā)基于小分子化合物的再生醫(yī)學(xué)療法，用于人類(lèi)疾病的治療。

研究成果

1、發(fā)現(xiàn)了一系列小分子化合物，能夠在誘導(dǎo)多能干細(xì)胞（iPS細(xì)胞）產(chǎn)生的過(guò)程中，取代外源轉(zhuǎn)錄因子和顯著提高重編程的效率/速度。通過(guò)研究這些小分子化合物，揭示了重編程過(guò)程的新機(jī)制。
2、開(kāi)發(fā)了一種全新的細(xì)胞轉(zhuǎn)分化技術(shù)（即譜系特異性重編程），在包含小分子化合物的特定條件下，可以把成纖維細(xì)胞轉(zhuǎn)變?yōu)槟軌驍U(kuò)增的心臟、神經(jīng)、血管內(nèi)皮、胰腺和肝臟細(xì)胞。
3、發(fā)現(xiàn)并從機(jī)制上鑒定了多個(gè)全新的小分子化合物，可以用于替換維持胚胎干細(xì)胞自我更新的生長(zhǎng)因子，促進(jìn)胚胎干細(xì)胞的生存，或者誘導(dǎo)胚胎干細(xì)胞向神經(jīng)、心臟和定形內(nèi)胚層譜系的分化。

榮譽(yù)和獎(jiǎng)勵(lì)

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.

代表性論文

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 na?ve 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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