The genome codes for “programs” of gene expression that give each cell type its unique identity. Precise control of gene expression ensures that cells develop, grow, and specialize correctly. Cancer corrupts this process to give rise to cells that uncontrollably multiply, grow and invade normal tissues.
The Lin lab uses molecular, computational and chemical biology approaches to study gene control in cancer.
We identify mechanisms that specify, activate, and repress genes that are altered in cancer. We strive to use this knowledge to develop therapeutic strategies targeting the gene control apparatus in cancer and other diseases.
Do;ctoral Thesis Title: c-Myc regulates transcriptional pause release and is a global amplifier of transcription
Publications while at MIT:
1. Models of human core transcriptional regulatory circuitries.
Saint-André V, Federation AJ, Lin CY, Abraham BJ, Reddy J, Lee TI, Bradner JE, Young RA.
Genome Res. 2016 Mar;26(3):385-96. doi: 10.1101/gr.197590.115. Epub 2016 Feb 3.PMID:26843070 Free PMC Article
2. Epigenomic analysis detects aberrant super-enhancer DNA methylation in human cancer.
Heyn H, Vidal E, Ferreira HJ, Vizoso M, Sayols S, Gomez A, Moran S, Boque-Sastre R, Guil S, Martinez-Cardus A, Lin CY, Royo R, Sanchez-Mut JV, Martinez R, Gut M, Torrents D, Orozco M, Gut I, Young RA, Esteller M.
Genome Biol. 2016 Jan 26;17:11. doi: 10.1186/s13059-016-0879-2. PMID: 26813288 Free PMC Article
3. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer.
Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, Janiszewska M, Huh SJ, Liang Y, Ryan J, Doherty E, Mohammed H, Guo H, Stover DG, Ekram MB, Peluffo G, Brown J, D’Santos C, Krop IE, Dillon D, McKeown M, Ott C, Qi J, Ni M, Rao PK, Duarte M, Wu SY, Chiang CM, Anders L, Young RA, Winer EP, Letai A, Barry WT, Carroll JS, Long HW, Brown M, Liu XS, Meyer CA, Bradner JE, Polyak K.
Nature. 2016 Jan 21;529(7586):413-7. doi: 10.1038/nature16508. Epub 2016 Jan 6.PMID: 26735014 Free PMC Article
4. Convergence of developmental and oncogenic signaling pathways at transcriptional super-enhancers.
Hnisz D, Schuijers J, Lin CY, Weintraub AS, Abraham BJ, Lee TI, Bradner JE, Young RA.
Mol Cell. 2015 Apr 16;58(2):362-70. doi: 10.1016/j.molcel.2015.02.014. Epub 2015 Mar 19.PMID: 25801169 Free PMC Article
Chapuy B, McKeown MR, Lin CY, Monti S, Roemer MG, Qi J, Rahl PB, Sun HH, Yeda KT, Doench JG, Reichert E, Kung AL, Rodig SJ, Young RA, Shipp MA, Bradner JE.
Cancer Cell. 2013 Dec 9;24(6):777-90. doi: 10.1016/j.ccr.2013.11.003. Erratum in: Cancer Cell. 2014 Apr 14;25(4):545-6. PMID: 24332044 Free PMC Article
6. SR proteins collaborate with 7SK and promoter-associated nascent RNA to release paused polymerase.
Ji X, Zhou Y, Pandit S, Huang J, Li H, Lin CY, Xiao R, Burge CB, Fu XD.
Cell. 2013 May 9;153(4):855-68. doi: 10.1016/j.cell.2013.04.028. PMID: 23663783. Free PMC Article
7. Selective inhibition of tumor oncogenes by disruption of super-enhancers.
Lovén J, Hoke HA, Lin CY, Lau A, Orlando DA, Vakoc CR, Bradner JE, Lee TI, Young RA.
Cell. 2013 Apr 11;153(2):320-34. doi: 10.1016/j.cell.2013.03.036. PMID: 23582323 Free PMC Article
8. Master transcription factors and mediator establish super-enhancers at key cell identity genes.
Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA.
Cell. 2013 Apr 11;153(2):307-19. doi: 10.1016/j.cell.2013.03.035.PMID: 23582322 Free PMC Article
9. Revisiting global gene expression analysis.
Lovén J, Orlando DA, Sigova AA, Lin CY, Rahl PB, Burge CB, Levens DL, Lee TI, Young RA.
Cell. 2012 Oct 26;151(3):476-82. doi: 10.1016/j.cell.2012.10.012. Review. PMID:23101621 Free PMC Article
10. Transcriptional amplification in tumor cells with elevated c-Myc.
Lin CY, Lovén J, Rahl PB, Paranal RM, Burge CB, Bradner JE, Lee TI, Young RA.
Cell. 2012 Sep 28;151(1):56-67. doi: 10.1016/j.cell.2012.08.026. PMID: 23021215 Free PMC Article
11. DHODH modulates transcriptional elongation in the neural crest and melanoma.
White RM, Cech J, Ratanasirintrawoot S, Lin CY, Rahl PB, Burke CJ, Langdon E, Tomlinson ML, Mosher J, Kaufman C, Chen F, Long HK, Kramer M, Datta S, Neuberg D, Granter S, Young RA, Morrison S, Wheeler GN, Zon LI.
Nature. 2011 Mar 24;471(7339):518-22. doi: 10.1038/nature09882.PMID: 21430780 Free PMC Article
12. c-Myc regulates transcriptional pause release.
Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, Sharp PA, Young RA.
Cell. 2010 Apr 30;141(3):432-45. doi: 10.1016/j.cell.2010.03.030. PMID: 20434984 Free PMC Article