丁勝（Ding S），男，漢族，教授。畢業於加州理工學院，現任清華大學藥學院院長，全球健康藥物研發中心主任，拜耳特聘教授。
基本介紹
- 中文名：丁勝
- 外文名：Ding S
- 別名：男
- 國籍：中國
- 民族：漢族
- 畢業院校：加州理工學院
- 職稱：教授
人物經歷,學術成就,研究成果,論文專著,研究方向,榮譽表彰,
人物經歷
1999年，在加州理工學院獲得化學學士學位。
2003年，在斯克里普斯研究所獲得化學博士學位。
2003年至2011年間，先後在斯克里普斯研究所化學系任職助理教授，副教授；
2011年，任職於美國加利福尼亞大學舊金山分校藥物化學系，在格拉德斯通研究所擔任冠名資深研究員及教授。丁勝教授開發和套用全新化學手段研究幹細胞和再生醫學，一直致力於發現和鑑定可以調控細胞命運和功能（例如，不同發育階段及不同組織中幹細胞的維持、激活、分化和重編程）的小分子化合物。
2016起，受聘於清華大學，擔任首任藥學院院長、拜耳特聘教授。
學術成就
丁勝教授實驗室以開發和套用全新的化學手段，解決在幹細胞和再生醫學研究中所面臨的各種挑戰聞名於世。通過不斷開發新的方法（例如，篩選技術或生物建模），丁勝教授研究團隊發現和鑑定了一系列能夠在體外和體內調控多種細胞命運（例如，幹細胞的維持，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調控特異性的細胞行為和表型，而這種變化在其他條件下極難或根本無法實現。另外，這些研究還發現了調控幹細胞的新概念和新機制。目前開展的小分子化合物誘導細胞重編程的研究，旨在體外和體內實現將一種類型的細胞轉變為同一組織或不同胚層的另一種細胞，將是細胞命運調控領域的一次巨大突破。這一研究將最終推動再生醫學藥物的出現，能夠在疾病或損傷後，通過喚醒和指導體內自身細胞，對組織和器官開展原位修復及再生。此外，這些研究成果已經被用於多家生物技術公司的創立，並推動了學術和生物製藥界開發基於小分子化合物的再生醫學療法，用於人類疾病的治療。
研究成果
1、發現了一系列小分子化合物，能夠在誘導多能幹細胞（iPS細胞）產生的過程中，取代外源轉錄因子和顯著提高重編程的效率/速度。通過研究這些小分子化合物，揭示了重編程過程的新機制。
2、開發了一種全新的細胞轉分化技術（即譜系特異性重編程），在包含小分子化合物的特定條件下，可以把成纖維細胞轉變為能夠擴增的心臟、神經、血管內皮、胰腺和肝臟細胞。
3、發現並從機制上鑑定了多個全新的小分子化合物，可以用於替換維持胚胎幹細胞自我更新的生長因子，促進胚胎幹細胞的生存，或者誘導胚胎幹細胞向神經、心臟和定形內胚層譜系的分化。
論文專著
截止2018年，丁勝教授已經發表了100多篇科研論文，研究綜述和書籍章節，並在幹細胞領域作出多項重要貢獻。此外，丁勝教授還作為共同創始人，參與創建了多家生物技術公司。
截止2018年，已發表了35篇原創性的、前沿性的文章，18篇評論及其他論著，擁有了16項專利，多次作為專家擔任美國多個重大基金或項目的評審。
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.
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, DingS. 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).
研究方向
丁勝博士具有合成化學、幹細胞生物學及藥物研發技術多元的專業背景，並創造性地開拓了“幹細胞化學生物學”這一前沿性新領域。
丁勝博士研究團隊早從2004年就開始進行小分子化合物誘導單功能細胞轉變為多功能細胞方面的研究，其團隊開創了用4個蛋白誘導ips的技術先河。這是“唯一”一個完全避免基因操作，避免改變基因組的ips誘導方法。在ips技術研究和發展中創造多個首例並成功首次合成小分子化合物QS11、Pluripotion和小分子化合物逆轉劑reversine.這些成果被Science、Nature、華爾街等著名媒體報導，部分成為美國一流的生物技術公司成立的基本概念。
該團隊在這一領域一直保持著領先。其中在一些方面第一次對生命科學領域的某些新的概念和技術進行了闡釋和解析。為其他學者們在接下來的研究中提供了重要的參考依據，啟發性意文。
丁博士在該學科的成就使得權威雜誌The Scientist在年度盤點中，兩度垂青這個青年科學家：丁勝博士所創的蛋白誘導ips技術被評為“年度最佳創新技術”，與此同時，丁勝博士也被The Scientist評選為“生命科學年度人物”。
丁勝教授實驗室致力於開發全新的化學方法，並將其用於幹細胞與再生醫學的研究，以期發現和鑑定可以調控細胞命運和功能（例如，不同發育階段及不同組織中幹細胞的維持、激活、分化和重編程）的全新小分子化合物。具體研究內容包括：（1）揭示幹細胞自我更新和多能性的機理；（2）誘導胚胎幹細胞向不同譜系（例如，神經、心臟、胰腺等）的分化；（3）人組織特異性幹細胞和祖細胞的定向分化；（4）研究細胞的可塑性和重編成過程（例如，生成iPS細胞、轉分化等）；（5）擴增無分裂能力的成體細胞（例如，心肌細胞、胰腺細胞等）；（6）解析參與胚胎髮育的信號通路（例如，Wnt、Hh、BMP、FGF等）以及表觀遺傳學（組蛋白和DNA的甲基化與去甲基化）的分子機制；（7）開發藥物發現的新技術。此外，丁勝教授研究團隊還會針對所發現的小分子化合物開展大量的工作，通過全面的構效關係分析、親和層析鑑定靶標、轉錄組學分析、蛋白質組學分析、化學/遺傳上位分析以及體外、體內生化和功能分析，對其分子機制進行研究。很多功能小分子化合物及其作用機制已經或正在被確定，它們能夠通過上述生物學過程之一對乾/祖細胞進行調節。這些研究將最終推動幹細胞的治療性套用，以及幫助開發能夠用於體內組織、器官再生或癌症治療的小分子藥物。
榮譽表彰
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.
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.
