Department of Molecular Medicine
 

Tim Huang Tim Hui-Ming  HuangPh.D.

Professor and Chair


Profile and Contact Information | Research | Laboratory


RESEARCH

 

Research Program

Dr. Huang has been conducting studies on cancer epigenetics for the last 17 years. He has pioneered the development of high-throughput technologies that are used to investigate molecular interactions between DNA methylation and histone modifications during tumorigenesis. Presently, Dr. Huang and his team members utilize next-generation sequencing approaches to decipher complex epigenetic profiles of various cancer subtypes. These omics approaches are used in combination with statistical and bioinformatic tools to develop biological models of epigenetic regulation of gene expression. In addition to studying epigenetic regulatory mechanisms, Dr. Huang has identified DNA methylation biomarkers that stratify clinicopathological subtypes of solid tumors. These biomarkers will be used to predict treatment outcomes of cancer patients undergoing Phase I clinical trials with combined inhibitors specifically targeting aberrant DNA methylation and oncogenic signaling.

 

Selected Publications

  1. Hsu PY, Hsu HK, Lan X, Juan L, Yan PS, Labanowska J, Heerema N, Hsiao TH, Chiu YC, Chen Y, Liu Y, Li L, Li R, Thompson IM, Nephew KP, Sharp ZD, Kirma NB, Jin VX, Huang TH. Amplification of distant estrogen response elements deregulates target genes associated with tamoxifen resistance in breast cancer. Cancer Cell. 2013 Aug 12;24(2):197-212.
  2. Hsu YT, Gu F, Huang YW, Liu J, Ruan J, Huang RL, Wang CM, Chen CL, Jadhav RR, Lai HC, Mutch DG, Goodfellow PJ, Thompson IM, Kirma NB, Huang TH. Promoter hypomethylation of EpCAM-regulated bone morphogenetic protein gene family in recurrent endometrial cancer. Clin Cancer Res. 2013 Nov 15;19(22):6272-85.
  3. Chen CL, Mahalingam D, Osmulski P, Jadhav RR, Wang CM, Leach RJ, Chang TC, Weitman SD, Kumar AP, Sun L, Gaczynska ME, Thompson IM, Huang TH. Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate. 2013 Jun;73(8):813-26.
  4. Huang TT, Gonzales CB, Gu F, Hsu YT, Jadhav RR, Wang CM, Redding SW, Tseng CE, Lee CC, Thompson IM, Chen HR, Huang TH, and Kirma NB: (2013) Epigenetic deregulation of the anaplastic lymphoma kinase gene modulates mesenchymal characteristics of oral squamous cell carcinomas. Carcinogenesis. 34(8): 1717-27.
  5. Matei D, Fang F, Shen C, Schilder J, Arnold A, Zeng Y, Berry WA, Huang T, and Nephew KP: (2012) Epigenetic resensitization to platinum in ovarian cancer. Cancer Res. 72(9): 2197-205.
  6. Cheng AS, Lau SS, Chen Y, Kondo Y, Li MS, Feng H, Ching AK, Cheung KF, Wong HK, Tong JH, Jin H, Choy KW, Yu J, To KF, Wong N, Huang TH, and Sung JJ: (2011) EZH2-mediated concordant repression of Wnt antagonists promotes beta-catenin-dependent hepatocarcinogenesis. Cancer Res. 71(11): 4028-39.
  7. Teng IW, Hou PC, Lee KD, Chu PY, Yeh KT, Jin VX, Tseng MJ, Tsai SJ, Chang YS, Wu CS, Sun HS, Tsai KD, Jeng LB, Nephew KP, Huang TH, Hsiao SH, and Leu YW: (2011) Targeted methylation of two tumor suppressor genes is sufficient to transform mesenchymal stem cells into cancer stem/initiating cells. Cancer Res. 71(13): 4653-63.
  8. Rodriguez BA, Weng YI, Liu TM, Zuo T, Hsu PY, Lin CH, Cheng AL, Cui H, Yan PS, and Huang TH: (2011) Estrogen-mediated epigenetic repression of the imprinted gene cyclin-dependent kinase inhibitor 1C in breast cancer cells. Carcinogenesis. 32(6): 812-21.
  9. Zuo T, Liu TM, Lan X, Weng YI, Shen R, Gu F, Huang YW, Liyanarachchi S, Deatherage DE, Hsu PY, Taslim C, Ramaswamy B, Shapiro CL, Lin HJ, Cheng AS, Jin VX, and Huang TH: (2011) Epigenetic silencing mediated through activated P13K/AKT signaling in breast cancer. Cancer Res. 71(5): 1752-62.
  10. Gu F, Hsu HK, Hsu PY, Wu J, Ma Y, Parvin J, Huang TH and Jin VX: (2010) Inference of hierarchical regulatory network of estrogen-dependent breast cancer through ChIP-based data. BMC Syst Biol. 4: 170.
  11. Huang TH and Esteller M: (2010) Chromatin remodeling in mammary gland differentiation and breast tumorigenesis. Cold Spring Harb Perspect Biol. 2(9): a004515.
  12. Weng YI, Hsu PY, Liyanarachchi S, Liu J, Deatherage DE, Huang YW, Zuo T, Rodriguez B, Lin CH, Cheng AL, and Huang TH: (2010) Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 248(2): 111-21.
  13. Hsu PY, Hsu HK, Singer GA, Yan PS, Rodriguez BA, Liu JC, Weng YI, Deatherage DE, Chen Z, Pereira JS, Lopez R, Russo J, Wang Q, Lamartiniere CA, Nephew KP, and Huang TH: (2010) Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping. Genome Res. 20(6): 733-44.
  14. Huang YW, Liu JC, Deatherage DE, Luo J, Mutch DG, Goodfellow PJ, Miller DS, and Huang TH: (2009) Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer. Cancer Res. 69(23): 9038-46.
  15. Weng YI, Huang TH, and Yan PS: (2009) Methylated DNA immunoprecipitation and microarray-based analysis: detection of DNA methylation in breast cancer cell lines. Methods Mol Biol. 590: 165-76.
  16. Hsu PY, Deatherage DE, Rodriguez BA, Liyanarachchi S, Weng YI, Zuo T, Liu J, Cheng AS, and Huang TH: (2009) Xenoestrogen-induced epigenetic repression of microRNA-9-3 in breast epithelial cells. Cancer Res. 69(14): 5936-45.
  17. Zhang S, Balch C, Chan MW, Lai HC, Matei D, Schilder JM, Yan PS, Huang TH, and Nephew KP: (2008) Identification and characterization of ovarian cancer-initiating cells from pimary human tumors. Cancer Res. 68(11): 4311-20.
  18. Davuluri RV, Suzuki Y, Sugano S, Plass C, and Huang TH: (2008) The functional consequences of alternative promoter use in mammalian genomes. Trends Genet. 24(4): 167-77.
  19. Kondo Y, Shen L, Cheng AS, Ahmed S, Boumber Y, Charo C, Yamochi T, Urano T, Furukawa K, Kwabi-Addo B, Gold DL, Sekido Y, Huang TH, and Issa JP: (2008) Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation. Nat Genet. 40(6): 741-50.
  20. Lin HJ, Zuo T, Lin CH, Kuo CT, Liyanarachchi S, Sun S, Shen R, Deatherage DE, Potter D, Asamoto L, Lin S, Yan PS, Cheng AL, Ostrowski MC, and Huang TH: (2008) Breast cancer-associated fibroblasts confer AKT1-mediated epigenetic silencing of Cystatin M in epithelial cells. Cancer Res. 68(24): 10257-66.
  21. Cheng AS, Culhane AC, Chan MW, Venkataramu CR, Ehrich M, Nasir A, Rodriguez BA, Liu J, Yan PS, Quackenbush J, Nephew KP, Yeatman TJ, and Huang TH: (2008) Epithelial progeny of estrogen-exposed breast progenitor cells display a cancer-like methylome. Cancer Res. 68(6): 1786-96.
  22. Estecio MR, Yan PS, Ibrahim AE, Tellez CS, Shen L, Huang TH, and Issa JP: (2007) High-throughput methylation profiling by MCA coupled to CpG island microarray. Genome Res. 17(10): 1529-36.
  23. Zuo T, Wang L, Morrison C, Chang X, Zhang H, Li W, Liu Y, Wang Y, Liu X, Chan MW, Liu JQ, Love R, Liu CG, Godfrey V, Shen R, Huang TH, Yang T, Park BK, Wang CY, Zheng P, and Liu Y: (2007) FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell. 129(7): 1275-86.
  24. Brena RM, Huang TH, and Plass C: (2006) Toward a human epigenome. Nat Genet. 38(12): 1359-60.
  25. Cheng AS, Jin VX, Fan M, Smith LT, Liyanarachchi S, Yan PS, Leu YW, Chan MW, Plass C, Nephew KP, Davuluri RV, and Huang TH: (2006) Combinatorial analysis of transcription factor partners reveals recruitment of c-MYC to estrogen receptor-alpha responsive promoters. Mol Cell. 21(3): 393-404.
  26. Yan PS, Venkataramu C, Ibrahim A, Liu JC, Shen RZ, Diaz NM, Centeno B, Weber F, Leu YW, Shapiro CL, Eng C, Yeatman TJ, and Huang TH: (2006) Mapping geographic zones of cancer risk with epigenetic biomarkers in normal breast tissue. Clin Cancer Res. 12(22): 6626-36.
  27. Gitan RS, Shi H, Chen CM, Yan PS, and Huang TH: (2002) Methylation-specific oligonucleotide microarray: a new potential for high-throughput methylation analysis. Genome Res. 12(1): 158-64.
  28. Huang TH, Perry MR, and Laux DE: (1999) Methylation profiling of CpG islands in human breast cancer cells. Hum Mol Genet. 8(3): 459-70.