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Shiqiang HUANG, Ph. D.

We are committed to studying the metabolic regulation of tissue aging and regeneration. Our main research directions include the differentiation of muscle stem cells, pathogenesis and treatment of sarcopenia in the elderly and cachexia in cancer patients, and the metabolic regulation of muscle regeneration.

Welcome to the Stem cell Regeneration and Metabolism research group!


Co-workers: Administration Staff: Ms. Ruirui Liu Postdoctoral Fellows: Dr. Zongmin Jiang, Dr. Taoyan Liu Graduate Students: Ms. Wenhua Cao, Mr. Yu Chen, Ms. Lu Guang, Ms. Kun Liang, Mr. Xupeng Liu, Ms. Lanfang Luo, Ms. Shilin Ma, Mr. Wenwu Ma, Mr. Peng Wang, Ms. Ziyue YaoUndergraduate Students: Ms. Luyao Guo, Ms. Liping Zhang

· HUANG Group website

 

Our research group is devoted to studying the mechanism of muscle aging and regeneration. Using skeletal muscle and other tissues as research models, we have carried out a series of stem cell metabolomics analyses to explore how to use fundamental metabolic principles to regulate cell fate. (1) To study how stem cell metabolism affects stem cell differentiation in tissue regeneration, we are using small molecules to induce human pluripotent stem cells to differentiate into muscle fibers. (2) To study the mechanisms of muscle wasting during aging, we are using human skeletal muscle fibers to model human muscle atrophy, and study the mechanisms of how different inflammatory cytokines and growth factors cause muscle wasting. We are committed to harnessing stem cell metabolism and regenerative medicine to treat muscle wasting syndromes and improve the quality of life of the elderly, in order to cope with the societal impact of aging.



Metabolic mechanisms that regulate stem cells and tissue regeneration

 

 

Plain english:
We are investigating stem cell metabolism during regeneration and aging, particularly in muscles. Our vision is to combine the latest advances in muscle stem cell biology with the latest technologies in metabolomics and next-generation sequencing, to understand how we can modulate metabolic systems to regulate muscle stem cell self-renewal and differentiation. Research in this direction will bring in important implications for treating degenerative metabolic diseases, such as type 2 diabetes and muscle wasting syndromes in aging populations. Towards this end, we have been using metabolomics technologies to direct our culture of muscle stem cells, and guide them to differentiate into mature muscle fibers in a dish.

 

Selected publications:

  1. Liu TM#, Yildirim ED, Li P, Fang HT, Denslin V, Kumar V, Loh YH, Lee EH, Cool SM, Teh BT, Hui JH, Lim B, Shyh-Chang N#. Ascorbate and iron are required for the specification and long-term self-renewal of human skeletal mesenchymal stromal cells. Stem Cell Reports, 2020, 14 (2), 210-225.
  2. Xu C, Ooi WF, Qamra A, Tan J, Chua BY, Ho SWT, Das K, Adam Isa ZF, Li Z, Yao X, Yan T, Xing M, Huang KK, Lin JS, Nandi T, Tay ST, Lee MH, Tan ALK, Ong X, Ashktorab H, Smoot D, Li S, Shyh-Chang N, Teh BT, Tan P. HNF4α pathway mapping identifies wild-type IDH1 as a targetable metabolic node in gastric cancer. Gut, 2020, 69(2):231-242.
  3. Liu T, Shyh-Chang N#. Oncofetal SALL4-driven tumorigenesis is highly dependent on oxidative phosphorylation, revealing therapeutic opportunities. Gastroenterology, 2019 157(6):1475-1477.
  4. Xu YJ, Liu PP, Ng SC, Teng ZQ, Liu CM. Regulatory networks between Polycomb complexes and non-coding RNAs in central nervous system. J Mol Cell Biol, 2019, mjz058.
  5. Jiang Z, Guang L, Li L, Shyh-Chang N#. Putting stem cells on a low-fat diet switches their pluripotent state. Cell Stem Cell, 2019, 25(1):3-5.
  6. Li CW, Yu K#Shyh-Chang N#, Li GX, Jiang LJ, Yu SL, Xu LY, Liu RJ, Guo ZJ, Xie HY, Li RR, Ying J, Li K, Li DJ. (2019). Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention. J Cachexia Sarcopenia Muscle, 2019, 10(3):586-600.
  7. Chua MJ, Yildirim ED, Tan JE, Chua YB, Low SC, Ding SLS, Li CW, Jiang Z, Teh BT, Yu K, Shyh-Chang N#. Assessment of different strategies for scalable production and proliferation of human myoblasts. Cell Prolif, 2019, 52(3):e12602.
  8. Zhang X, Liu Z, Liu X, Wang S, Zhang Y, He X, Sun S, Ma S, Shyh-Chang N, Liu F, Wang Q, Wang X, Liu L, Zhang W, Song M, Liu GH, Qu J. Telomere-dependent and telomere-independent roles of RAP1 in regulating human stem cell homeostasis. Protein Cell, 2019, 10(9):649-667.
  9. Usman WM, Pham TC, Kwok YY, Vu LT, Ma V, Peng B, Chan YS, Wei L, Chin SM, Azad A, He AB, Leung AYH, Yang M, Shyh-Chang N, Cho WC, Shi J, Le MTN. Efficient RNA drug delivery using red blood cell extracellular vesicles. Nat Commun, 2018, 9(1):2359.
  10. Shyh-Chang N#. Metabolic changes during cancer cachexia pathogenesis. Adv Exp Med Biol, 2017, 1026:233-249.
  11. Lee HJ, Jedrychowski MP, Vinayagam A, Wu N, Shyh-Chang N, Hu Y, Min-Wen C, Moore JK, Asara JM, Lyssiotis CA, Perrimon N, Gygi SP, Cantley LC, Kirschner MW. Proteomic and metabolomic characterization of a mammalian cellular transition from quiescence to proliferation. Cell Rep, 2017, 20(3):721-736.
  12. Liu TM, Shyh-Chang N#. SIRT2 and glycolytic enzyme acetylation in pluripotent stem cells. Nat Cell Biol, 2017, 19(5):412-414.
  13. Andriani Y, Chua JM, Chua BY, Phang IY, Shyh-Chang N#, Tan WS#. Polyurethane acrylates as effective substrates for sustained in vitro culture of human myotubes. Acta Biomater, 2017, 57:115-126.
  14. Min-Wen JC, Yan-Jiang BC, Mishra S, Dai X, Magae J, Shyh-Chang N#, Kumar AP#, Sethi G#. Molecular targets of ascochlorin and its derivatives for cancer therapy. Adv Protein Chem Struct Biol, 2017, 108:199-225.
  15. Shyh-Chang N#, Ng HH#. The metabolic programming of stem cells. Genes Dev, 2017, 31(4):336-346.
  16. Loh KM, Chen A, Koh PW, Deng TZ, Sinha R, Tsai JM, Barkal AA, Shen KY, Jain R, Morganti RM, Shyh-Chang N, Fernhoff NB, George BM, Wernig G, Salomon REA, Chen Z, Vogel H, Epstein JA, Kundaje A, Talbot WS, Beachy PA, Ang LT, Weissman IL. Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types. Cell, 2016, 166(2):451-467.
  17. Zhang WC, Chin TM, Yang H, Nga ME, Lunny DP, Lim EK, Sun LL, Pang YH, Leow YN, Malusay SR, Lim PX, Lee JZ, Tan BJ, Shyh-Chang N, Lim EH, Lim WT, Tan DS, Tan EH, Tai BC, Soo RA, Tam WL, Lim B. Tumour-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression. Nat Commun, 2016, 7:11702.
  18. Zhang J, Ratanasirintrawoot S, Chandrasekaran S, Wu Z, Ficarro SB, Yu C, Ross CA, Cacchiarelli D, Xia Q, Seligson M, Shinoda G, Xie W, Cahan P, Wang L, Ng SC, Tintara S, Trapnell C, Onder T, Loh YH, Mikkelsen T, Sliz P, Teitell MA, Asara JM, Marto JA, Li H, Collins JJ, Daley GQ. LIN28 Regulates Stem Cell Metabolism and Conversion to Primed Pluripotency. Cell Stem Cell, 2016, 19(1):66-80.
  19. Fukawa T, Yan-Jiang BC, Min-Wen JC, Jun-Hao ET, Huang D, Qian CN, Ong P, Li Z, Chen S, Mak SY, Lim WJ, Kanayama HO, Mohan RE, Wang RR, Lai JH, Chua C, Ong HS, Tan KK, Ho YS, Tan IB#, Teh BT#Shyh-Chang N#. Excessive fatty acid oxidation induces muscle atrophy in cancer cachexia. Nat Med, 2016, 22(6):666-71.
  20. Tan JL, Fogley RD, Flynn RA, Ablain J, Yang S, Saint-André V, Fan ZP, Do BT, Laga AC, Fujinaga K, Santoriello C, Greer CB, Kim YJ, Clohessy JG, Bothmer A, Pandell N, Avagyan S, Brogie JE, van Rooijen E, Hagedorn EJ, Shyh-Chang N, White RM, Price DH, Pandolfi PP, Peterlin BM, Zhou Y, Kim TH, Asara JM, Chang HY, Young RA, Zon LI. Stress from nucleotide depletion activates the transcriptional regulator HEXIM1 to suppress melanoma. Mol Cell, 2016, 62(1):34-46.
  21. Min-Wen JC, Jun-Hao ET, Shyh-Chang N#. Stem cell mitochondria during aging. Semin Cell Dev Biol, 2016, 52:110-8.
  22. Jun-Hao ET, Gupta RR, Shyh-Chang N#. Lin28 and let-7 in the metabolic physiology of aging. Trends Endocrinol Metab, 2016, 27(3):132-141.
  23. Liu TM#, Lee EH, Lim B#Shyh-Chang N#. Balancing stem cell self-renewal and differentiation with PLZF. Stem Cells, 2016, 34(2):277-87.
  24. Wu L, Nguyen LH, Zhou K, de Soysa TY, Li L, Miller JB, Tian J, Locker J, Zhang S, Shinoda G, Seligson MT, Zeitels LR, Acharya A, Wang SC, Mendell JT, He X, Nishino J, Morrison SJ, Siegwart DJ, Daley GQ, Shyh-Chang N, Zhu H. Precise let-7 expression levels balance organ regeneration against tumor suppression. Elife, 2015, 4:e09431.
  25. Khaw SL, Min-Wen C, Koh CG#, Lim B#Shyh-Chang N#. Oocyte factors suppress mitochondrial polynucleotide phosphorylase to remodel the metabolome and enhance reprogramming. Cell Rep, 2015, 12(7):1080-8.
  26. Shyh-Chang N, Daley GQ. Metabolic switches linked to pluripotency and embryonic stem cell differentiation. Cell Metab, 2015, 21(3):349-50.
  27. Shyh-Chang N, Zhu H, Yvanka de Soysa T, Shinoda G, Seligson MT, Tsanov KM, Nguyen L, Asara JM, Cantley LC, Daley GQ. Lin28 enhances tissue repair by reprogramming cellular metabolism. Cell, 2013, 155(4):778-92.
  28. Shyh-Chang N, Daley GQ, Cantley LC. Stem cell metabolism in tissue development and aging. Development, 2013, 140(12):2535-47.
  29. Shinoda G, Shyh-Chang N, Soysa TY, Zhu H, Seligson MT, Shah SP, Abo-Sido N, Yabuuchi A, Hagan JP, Gregory RI, Asara JM, Cantley LC, Moss EG, Daley GQ. Fetal deficiency of lin28 programs life-long aberrations in growth and glucose metabolism. Stem Cells, 2013, 31(8):1563-73.
  30. Shyh-Chang N, Daley GQ. Lin28: primal regulator of growth and metabolism in stem cells. Cell Stem Cell, 2013, 12(4):395-406.
  31. Son J, Lyssiotis CA, Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, Cantley LC, Kimmelman AC. Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway. Nature, 2013, 496(7443):101-5.
  32. Shyh-Chang N, Locasale JW, Lyssiotis CA, Zheng Y, Teo RY, Ratanasirintrawoot S, Zhang J, Onder T, Unternaehrer JJ, Zhu H, Asara JM, Daley GQ, Cantley LC. Influence of threonine metabolism on S-adenosylmethionine and histone methylation. Science, 2013, 339(6116):222-6.
  33. Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, Soh BS, Sun LL, Tai BC, Nga ME, Bhakoo KK, Jayapal SR, Nichane M, Yu Q, Ahmed DA, Tan C, Sing WP, Tam J, Thirugananam A, Noghabi MS, Pang YH, Ang HS, Mitchell W, Robson P, Kaldis P, Soo RA, Swarup S, Lim EH, Lim B. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell, 2012, 148(1-2):259-72.
  34. Shyh-Chang N, Zheng Y, Locasale JW, Cantley LC. Human pluripotent stem cells decouple respiration from energy production. EMBO J, 2011, 30(24):4851-2.
  35. Zhu H*Shyh-Chang N*, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI; DIAGRAM Consortium; MAGIC Investigators, Altshuler D, Daley GQ. The Lin28/let-7 axis regulates glucose metabolism. Cell, 2011, 147(1):81-94.
  36. Le MT*Shyh-Chang N*, Khaw SL, Chin L, Teh C, Tay J, O'Day E, Korzh V, Yang H, Lal A, Lieberman J, Lodish HF, Lim B. Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs. PLoS Genet, 2011, 7(9):e1002242.
  37. Zhu H, Shah S, Shyh-Chang N, Shinoda G, Einhorn WS, Viswanathan SR, Takeuchi A, Grasemann C, Rinn JL, Lopez MF, Hirschhorn JN, Palmert MR, Daley GQ. Lin28a transgenic mice manifest size and puberty phenotypes identified in human genetic association studies. Nat Genet, 2010, 42(7):626-30.
  38. Le MT, Teh C*Shyh-Chang N*, Xie H, Zhou B, Korzh V, Lodish HF, Lim B. MicroRNA-125b is a novel negative regulator of p53. Genes Dev, 2009, 23(7):862-76