Our team is interested in cancer-causing transcription factors. Transcription factors are genes that control the levels of other genes. This gene regulation is crucial for the development of embryos into full grown adults, and for maintaining good health in adults. Many of these factors become dysregulated in cancer and they become strong drivers of tumor growth. Unfortunately, close to 90% of transcription factors remain undruggable.
Through a combination of genomic and molecular biology techniques, we seek to better understand how transcription factors promote cancer through dysregulation of gene expression. Since many of these transcription factors are important for maintaining normal cell functions, it is important to understand the context in which they become cancer-causing. From this knowledge, we can identify vulnerabilities created by these transcription factors, in the context of cancer, for therapeutic development.
Complementary to our functional studies of cancer-causing transcription factors, we are developing high-throughput screening approaches, rooted in Chemical Biology, to identify probe compounds that target these transcription factors and their dependencies. These probes not only serve as proof-of-concept that transcription factors can be drugged, but they also provide invaluable tools for studying the novel biology underlying the cancer-driving ability of these factors. Through our science, we strive to contribute to better outcomes for cancer patients.
- Tan JL, Li F, Yeo JZ, Yong KJ, Bassal MA, Ng GH, Lee MY, Leong CY, Tan HK, Wu CS, Liu BH, Chan TH, Tan ZH, Chan YS, Wang S, Lim ZH, Toh TB, Hooi L, Low KN, Ma S, Kong NR, Stein AJ, Wu Y, Thangavelu MT, Suzuki A, Periyasamy G, Asara JM, Dan YY, Bonney GK, Chow EK, Lu G, Ng HH, Kanagasundaram Y, Ng SB, Tam WL, Tenen DG & Chai L. New High-throughput Screen Identifies Compounds That Reduce Viability Specifically In Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation. Gastroenterology 2019 Aug 22. pii: S0016-5085(19)41242-0. doi: 10.1053/j.gastro.2019.08.022. Abstract
- Sun W, Dai L, Yu H, Puspita B, Zhao T, Li F, Tan JL, Lim YT, Chen MW, Sobota RM, Tenen DG, Prabhu N, Nordlund P "Monitoring structural modulation of redox-sensitive proteins in cells with MS-CETSA." Redox Biol 2019 Jun ; 24 : 101168 Abstract
- 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 Apr 07 ; 62(1) : 34-46 Abstract
- Kaufman CK, Mosimann C, Fan ZP, Yang S, Thomas AJ, Ablain J, Tan JL, Fogley RD, van Rooijen E, Hagedorn EJ, Ciarlo C, White RM, Matos DA, Puller AC, Santoriello C, Liao EC, Young RA, Zon LI "A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation." Science 2016 Jan 29 ; 351(6272) : aad2197 Abstract
- Tan JL, Zon LI "Chemical screening in zebrafish for novel biological and therapeutic discovery." Methods Cell Biol 2011 ; 105 : 493-516 Abstract