NG Shi Yan

Ng_Shi_Yan@a-star.edu.sg

RESEARCH

The Ng laboratory pioneers the use of human stem cell-derived brain and spinal organoids to decode the mechanisms of neurodegenerative and neurological diseases. By integrating stem cell biology, organoid engineering and multi-omics approaches, we develop robust human models that capture the complexity of disease biology – with the ultimate goal of identifying and advancing disease-modifying therapies.

Disease Modeling 2.0: Functionally Integrating the Nervous System with Immune Cells and Peripheral Tissues

Tissues and organs do not function in insolation. The brain and spinal cord, for example, are intimately associated with resident immune cells such as microglia, while peripheral organs are dynamically regulated by networks of peripheral nerves, including sympathetic and parasympathetic neurons, that finetune physiological responses.

Selected Publications

• Chooi WH, Winanto, Zeng Y, Lee CY, Lim ZQ, Gautam P, Chu JJH, Loh YH, Alonso S, Ng SY^# (2024). Enterovirus-A71 preferentially infects and replicates in human motor neurons, inducing neurodegeneration by ferroptosis. Emerg Microbes Infect. 13(1):2382235. ^#corresponding author
  

• Feng J, Chuah YH, Liang Y, Cipta NO, Zeng Y, Warrier T, Elsayed Elfar GAR, Yoon J, Grinchuk OV, Tay EXY, Lok KZ, Zheng ZQ, Khong ZJ, Chong ZS, Teo J, Sanford EM, Neo CJY, Chui HY, Leung JY, Wang LC, Lim YT, Zhao T, Sobota RM, Crasta KC, Tergaonkar V, Taneja R, Ng SY, Cheok CF, Ling SC, Loh YH, Ong DST (2024). PHF1 regulates genome topology and DNA replication in neural stem cells via cohesion. Nucleic Acids Res. 52(12):7063-7080.
  

• Leow DMK, Ng YK, Wang LC, Koh HWI, Zhao T, Khong ZJ, Tabaglio T, Narayanan G, Giadone RM, Sobota RM, Ng SY, Teo AKK, Parson SH, Rubin LL, Ong WY, Darras BT, Yeo CJJ (2024). Hepatocyte-intrinsic SMN deficiency drives metabolic dysfunction and liver steatosis in spinal muscular atrophy. J Clin Invest. 134(12):e173702.
  

• Nguyen TD, Chooi WH, Jeon H, Chen J, Roxby DN, Tan JZY, Lee CY, Ng SY, Chew SY, Han J (2024). Label-free and high-throughput removal of residual undifferentiated cells from iPSC-derived spinal cord progenitor cells. Stem Cells Transl Med. 13(4):387-398.
  

• Goh M, Fu L, Seetoh WG, Koay A, Huang H, Tan SM, Tay SH, Chin EJ, Abdullah N, Ng SY, Lakshmanan M, Aramugam P (2024). Mono-2-ethylhexylphthalate (MEHP) is a potent agonist of human TRPA1 channel. Chemosphere 349:140740.
  

• Harley J, Santosa MM, Ng CY, Grinchuk OV, Hor JH, Liang Y, Lim VJW, Tee WW, Ong DST, Ng SY^# (2024). Telomere shortening induces aging-associated phenotypes in hiPSC-derived neurons and astrocytes. Biogerontology 25(2):341-360. ^#corresponding author
  

• Kwokdinata C, Ramanujam V, Chen J, de Oliveira PN, Nai MH, Chooi WH, Lim CT, Ng SY, David L, Chew SY (2023). Encapsulation of Human Spinal Cord Progenitor Cells in Hyaluronan-Gelatin Hydrogel for Spinal Cord Injury Treatment. ACS Appl Mater Interfaces doi: 10.1021/acsami.3c07419.
  

• Ho WY, Chak LL, Hor JH, Liu F, Diaz-Garcia S, Chang JC, Sanford EM, Rodriguez MJ, Alagappan D, Lim SM, Cho YL, Shimizu Y, Sun AX, Tyan SH, Koo E, Kim SH, Ravits J, Ng SY, Okamura K, Ling SC (2023). FUS-dependent microRNA deregulations identify TRIB2 as a druggable target for ALS motor neurons. iScience 26(11):108152.
  

• Lee CY, Chooi WH, Ng SY, Chew SY (2023).  Modulating neuroinflammation through molecular, cellular and biomaterial-based approaches to treat spinal cord injury. Bioeng Transl Med. Aug 31; 8(2):e10389.
  

• Chooi WH, Ng CY, Ow V, Ng W, Hor JH, Low KE, Malleret B, Xue K, Ng SY^# (2023). Defined alginate hydrogels support spinal cord organoid derivation, maturation, and modeling of spinal cord diseases. Adv Healthc Mater. Apr;12(9):e2202342. ^#corresponding author
  

• Ow V, Chang JJ, Chooi WH, Boo YJ, Tan RPT, Wong JHM, Parikh BH, Su X, Ng SY, Loh XJ, Xue K (2023). Orthogonally crosslinked alginate conjugate thermogels with potential for cell encapsulation. Carbohydr Polym. 302:120308
  

• Ng W, Ng SY^# (2022). Remodeling of astrocyte secretome in amyotrophic lateral sclerosis: uncovering novel targets to combat astrocyte-mediated toxicity. Transl Neurodegener. 26;11(1):54. ^#corresponding author
  

• Agrawal I, Lim YS, Ng SY, Ling SC (2022). Deciphering lipid dysregulation in ALS: from mechanisms to translational medicine. Transl. Neurodegener. 26;11(1):48
  

• Chong ZS, Khong ZJ, Tay SH, Ng SY^# (2022). Metabolic contributions to neuronal deficits caused by genomic disruption of schizophrenia risk gene SETD1A. Schizophrenia 8(1):115. ^#corresponding author
  

• Ho BX, Pang JKS, Chen Y, Loh YH, An O, Yang HH, Seshachalam VP, Koh JLY, Chan WK, Ng SY, Soh BS (2022). Robust generation of human-chambered cardiac organoids from pluripotent stem cells for improved modeling of cardiovascular diseases. Stem Cell Res Ther. 13(1):529.
  

• Pang JKS, Chia S, Zhang J, Szyniarowski P, Stewart CL, Yang HH, Chan WK, Ng SY, Soh BS (2022). Characterizing arrhythmia using machine learning analysis of Ca2+ cycling in human cardiomyocytes. Stem Cell Rep. 17(8):1810-1823.
  

• Ho BX, Pang JKS, Hor JH, Liew LC, Szyniarowski P, Lim CYY, An O, Yang HH, Stewart CL, Chan WK, Ng SY, Soh BS (2021). Upregulation of the JAK-STAT pathway promotes maturation of human embryonic stem cell-derived cardiomyocytes. Stem Cell Rep. 16:2928-2941.
  

• Yoon J, Grinchuk OV, Kannan S, Ang MJY, Li Z, Tay EXY, Lok KZ, Lee BWL, Chuah YH, Chia K, Magallanes RT, Liu C, Zhao H, Hor JH, Lim JJ, Benoukraf T, Toh TB, Chow EKH, Kovalik JP, Ching J, Ng SY, Koh MJ, Liu X, Verma C, Ong DST (2021). A chemical biology approach reveals a dependency of glioblastoma on carboxylase activation. Science Adv. 7(36):eabf6033.
  

• Ho WY, Chang JC, Lim K, Cazenave-Gassiot A, Nguyen A, Foo JC, Muralidharan S, Viera-Ortiz A, Ong S, Hor JH, Agrawal I, Hoon S, Arogundade OA, Rodriguez M, Lim SM, Kim SH, Ravits J, Ng SY, Wenk M, Lee E, Tucker Kellogg G, Ling SC (2021). TDP-43 mediates SREBF2-regulated gene expression required for oligodendrocyte myelination. Journal Cell Biol. 220(9):e201910213.
  

• Hor JH, Santosa MM, Lim VJW, Ho BX, Taylor A, Khong ZJ, Ravits J, Fan Y, Liou YC, Soh BS, Ng SY^# (2021). ALS motor neurons exhibit hallmark metabolic defects that are rescued by SIRT3 activation. Cell Death Differ. 28(4):1379-1397. ^#corresponding author