Angela H Ting Ph.D.

Associate Staff

  • Genomic Medicine Institute
  • Lerner Research Institute
  • 9500 Euclid Avenue
  • Cleveland, Ohio 44195
  • tinga@ccf.org
  • Phone: (216) 444-0682
  • Fax: (216) 636-0009

Epigenetic gene regulation is important for both normal development as well as disease states. In cancers, aberrant promoter CpG island hypermethylation correlates highly with gene inactivation and can account for lack of gene expression where mutations do not exist.  In addition to cancer, epigenetic aberrations are suspected to be involved in the pathogenesis of other human diseases, but such abnormalities remain to be described fully.  We are interested in dissecting the mechanisms of epigenetic gene silencing and understanding the functional relevance of DNA methylation in diseases.

RNA-dependent Transcriptional Silencing (RdTS) mechanism

Synthetic small double-stranded RNAs targeted exclusively to promoter regions of genes can effectively trigger transcriptional silencing in human immortalized cells. This finding indicates that the machineries for RdTS are present in human cells to initiate epigenetic silencing. We are identifying the endogenous targets/triggers of RdTS to delineate this pathway.

Comprehensive survey of DNA methylation patterns in cancer

DNA methylation abnormalities have been well-documented in many types of cancer.  We propose to use MBD-isolated Genome Sequencing (MiGS) to provide a comprehensive description of DNA methylation patterns in different cancers to facilitate the development of biomarkers as well as to guide biological studies.  We are currently mapping DNA methylation profiles in colon and prostate cancers.

In other words ...

Epigenetics are modifications on top of the DNA sequences and regulate expression of the DNA within each cell of the body as required for normal development and functioning.  However, these modifications become abnormal during the initiation, development, and progression of human cancers.  We know that some of these cancer-specific epigenetic changes work like molecular switches that turn off specific caretaker genes, whose function is to safeguard the genome and prevent inappropriate proliferation, to facilitate cancer cell formation and growth. With the recent advances in technologies, we are now able to map the epigenetic differences between normal and cancer cells at a genomic scale with high efficiency. These comprehensive epigenomic profiles enable us to understand the cause, function, and consequence of cancer-specific epigenetic changes.  Such knowledge is crucial to developing prevention, screening, and treatment strategies for various types of cancers.  In particular, we are focusing our efforts on the studies of prostate and colon cancers. 

  • Jeffrey Bhasin
  • Graduate Student
  • Location:NE5-250
  • Phone:(216) 445-3385
  • bhasinj@ccf.org
  • Thomas Sweet PhD
  • Postdoctoral Research Fellow
  • Location:NE5-250
  • Phone:(216) 445-3385
  • Fax:(216) 636-0009
  • sweett2@ccf.org
  • Nagarajavel Vivekananthan PhD
  • Postdoctoral Research Fellow
  • Location:NE5-250
  • Phone:(216) 445-3385
  • Fax:(216) 636-0009
  • vivekan@ccf.org

  • Lee BH, et al. Dysregulation of cholesterol homeostasis in human prostate cancer through loss of ABCA1. Cancer Res. 2013;73:1211-8. *Recommended by the Faculty of 1000*
  • Xu Y, et al. Unique DNA methylome profiles in CpG island methylator phenotype colon cancers. Genome Res. 2012; 22:283-291.
  • Yan H, Choi AJ, Lee BH, Ting AH. Identification and functional analysis of epigenetically silenced microRNAs in colorectal cancer cells. PLoS One. 2011; 6:e20628.
  • Serre D, Lee BH, Ting AH. MBD-isolated Genome Sequencing provides a high-throughput and comprehensive survey of DNA methylation in the human genome. Nucleic Acids Res. 2010; 38: 391-399.
  • Ting AH, et al. A requirement for DICER to maintain full promoter CpG island hypermethylation in human cancer cells. Cancer Res. 2008; 68:2570-2575.
  • Ting AH, et al. Short double-stranded RNA induces transcriptional gene silencing in human cancer cells in the absence of DNA methylation. Nat Genet. 2005; 37:906-910.