Sheng Ding

 

E-mail: shengding@tsinghua.edu.cn

Phone: +86-10-62795022

 

Research Area:

My lab has been developing and applying innovative chemical approaches to stem cell biology and regeneration, with a focus on discovering and characterizing novel small molecules that can control cell fate and function of various cell types, including stem cell maintenance, activation, differentiation and reprogramming in various developmental stages and tissues. Specific projects include (1) Self-renewal regulation of embryonic and adult stem cells; (2) Directed and step-wised differentiation of embryonic stem cells toward neuronal, cardiac and pancreatic lineages; (3) Subtype specification of human tissue-specific stem/progenitor cells; (4) Cellular plasticity and reprogramming of lineage-restricted somatic cells to alternative cell fate (e.g., toward iPSCs or transdifferentiation); (5) Functional proliferation of adult cardiomyocytes and pancreatic beta cells; (6) Developmental signaling pathways (i.e. Wnt, Hh, BMP and FGF) and epigenetic mechanisms (histone and DNA de/methylation); (7) Development of new technologies for drug discovery. Moreover, major efforts are devoted to characterize the molecular mechanism of these identified small molecules using various approaches, including detailed structure-activity-relationship (SAR) studies, affinity chromatography for target identification, transcriptome profiling, proteomics analysis, chemical/genetic epistasis, and biochemical and functional assays in vitro and in vivo. So far, functional small molecules and fundamental mechanisms have been identified and are being characterized in each of the above twenty plus distinct biological processes involving regulation of stem/progenitor cells. Those studies may ultimately facilitate the therapeutic application of stem cells and the development of small molecule drugs to stimulate tissue and organ regeneration in vivo, or treating cancers.

 

Selected Publications:

1.      An Z, Liu P, Zheng J, Si C, Li T, Chen Y, Ma T, Zhang MQ, Zhou Q, Ding S. Sox2 and Klf4 as the Functional Core in Pluripotency Induction without Exogenous Oct4. Cell Rep, 2019, 29(7):1986-2000.

2.      Peng Liu, Meng Chen, Yanxia Liu, Lei S. Qi, Sheng Ding. CRISPR Remodeling of Endogenous Oct4 or Sox2 Chromatin Locus Enables Reprogramming to Pluripotency. Cell Stem Cell 22, 252-261, (2018).

3.      Xu T, Stewart KM, Wang X, Liu K, Xie M, Kyu Ryu J, Li K, Ma T, Wang H, Ni L, Zhu S, Cao N, Zhu D, Zhang Y, Akassoglou K, Dong C, Driggers EM, Ding S. Metabolic control of TH17 and induced Treg cell balance by an epigenetic mechanism. Nature 548(7666):228-233, (2017).  

4.      Nie B, Nie T, Hui X, Gu P, Mao L, Li K, Yuan R, Zheng J, Wang H, Li K, Tang S, Zhang Y, Xu T, Xu A, Wu D, Ding S. Brown Adipogenic Reprogramming Induced by a Small Molecule. Cell Rep. 18(3):624-635, (2017).

5.      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 352(6290):1216-20, (2016).

6.      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 18(5):653-67, (2016).

7.      Yu Zhang, Nan Cao, Yu Huang, C. Ian Spencer, Ji-dong Fu, Chen Yu, Kai Liu, Baoming Nie, Tao Xu, Ke Li, Shaohua Xu, Benoit G. Bruneau, Deepak Srivastava, Sheng Ding. Expandable Cardiovascular Progenitor Cells Reprogrammed from Fibroblasts. Cell Stem Cell 18, 368–381, 2016.

8.      Saiyong Zhu, Holger A. Russ, Xiaojing Wang, Mingliang Zhang, Tianhua Ma, Tao Xu, Shibing Tang, Matthias Hebrok, Sheng Ding Human pancreatic beta-like cells converted from fibroblasts. Nat Commun. 7, doi:10.1038/ncomms10080, 2016.

9.      Ma T, Li J, Xu Y, Yu C, Xu T, Wang H, Liu K, Cao N, Nie B, Zhu S, Xu S, Li K, Wei W, Wu Y, Guan K & Ding S Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming. Nature Cell Biology 17(11):1379-87, 2015.

10.  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(2):142-7, (2015).