Yan Dai, Ph.D.
PI: Yan Dai
Title: Assistant Professor
Research interests: Epigenetic mechanisms in cancer development and progression
Contact: Cancer Center
Boston University School of Medicine
72 East Concord Street, L913
Boston, MA. 02118
Office phone: 617-618-5650
Lab phone: 617-414-8411
My research interest is to uncover novel molecular mechanisms of cancer development and progression in order to develop novel strategies for cancer treatment, with particular interest in epigenetic mechanisms and the roles of class III HDACs in cancer cell growth and metastasis. There are two focus areas among my research interests:
1. The Epigenetic Modification: Impact on Cancer Pathology
Epigenetic regulation has been shown to be a critical mechanism in cancer development and progression. Among these epigenetic modifications are histone acetylation, methylation, phosphorylation, and DNA methylation, and the enzymes responsible for these modifications are poised to take center stage in the study of cancer. My research focuses on the role of class III histone deacetylases and their interplay partners including the SWI/SNF chromatin remodeling complex (Brg1/Brm), DNA methyltransferases, histone demethylase (LSD1), and polycomb group proteins (EZH2 and SUZ12) in epigenetic regulation during cancer development and progression. We use epigenetic approaches e.g. Chromatin Immunoprecipitation assays (ChIPs) and Methylation Specific PCR (MSP) to study how class III HDACs cooperate with their epigenetic modifier partners to regulate tumor suppressor gene silencing during cancer cell growth, metastasis, as well as in prostate and breast cancer recurrence.
II. The Functional Role of SIRT1 in Cancer Growth and Metastasis
SIRT1 is one of the nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (class III HDAC), which plays an important role in a variety of physiological process, including apoptosis, calorie restriction, organ metabolism, cellular senescence, and aging, due to its ability to deacetylate both histone and non-histone substrates.
Our recent in vitro and in vivo studies have shown that SIRT1 promotes prostate and breast cancer cell migration/invasion, and lung cancer cell growth. We have demonstrated that SIRT1 induces epithelial-to-mesenchymal transition (EMT), a crucial program for invasion and metastasis in many epithelial tumors, and that SIRT1 enhances prostate cancer cell metastasis in vivo. Our ongoing studies focus on further elucidating the role of SIRT1 in cancer metastasis and studying the mechanism by which SIRT1 regulates EMT during cancer progression by using in vitro molecular and cell biology approaches, and in vivo mouse models, including conditional SIRT1 knockout mouse models and orthotopic cancer xenograft mouse models. We also develop more potent SIRT1 inhibitors to be used for cancer treatments including the treatment of prostate, lung and breast cancer.
Byles V, Zhu LJ, Lovaas J, Chmilewski LK, Wang J, Faller DV, Dai Y*. SIRT1 induces EMT by cooperating with EMT transcription factors and enhances prostate cancer cell migration and metastasis. Oncogene. 2012 Jan 16. PMID: 22249256
Moore R, Dai Y and Faller DV. SIRT1 and Steroid Hormone Receptor Activity in Cancer. J Endocrinol. 2011 Dec 12. PMID: 22159506
Byles V, Chmilewski LK, Wang J, Zhu L, Forman LW, Faller DV and Dai Y*. Aberrant Cytoplasm Localization and Protein Stability of SIRT1 is Regulated by PI3K/IGF-1R Signaling in Human Cancer Cells. Int J Biol Sci., 2010; 6(6):599-612. PMID: 20941378
Dai Y *, Ngo DY, Jacob J, Forman LW, and Faller DV. Prohibitin and the SWI/SNF ATPase Subunit BRG1 are Required for Androgen-antagonist-mediated Transcriptional Repression of Androgen Receptor-regulated Genes. Carcinogenesis. 2008 Sep; 29 (9):1725-33. PMID: 18487222
Dai Y * and Faller DV. Transcription Regulation by Class III Histone Deacetylases (HDACs) – Sirtuins. Translational Oncogenomics. 2008 3: 53-65. PMID: 21566744
Dai Y*, Ngo DY, Forman LC, Qin S, Jacob J and Faller DV. SIRT1 is required for antagonist-induced transcriptional repression of androgen-responsive genes by the androgen receptor. Molecular Endocrinology. 2007 Aug; 21(8):1807-21. PMID: 17505061
Ye B, Aponte M, Dai Y, Li L, Ho MC, Vitonis A, Edwards D, Huang TN, Cramer DW.
Ginkgo biloba and ovarian cancer prevention: Epidemiological and biological evidence.
Cancer Lett. 2007 Jun 18; 251(1):43-52. PMID: 17194528
Dai Y, Wong B, Yen YM, Oettinger MA, Kwon J, Johnson RC. Determinants of HMGB Proteins Required To Promote RAG1/2-Recombination Signal Sequence Complex Assembly and Catalysis during V (D) J Recombination. Mol Cell Biol. 2005 Jun; 25(11):4413-25. PMID: 15899848
Dai Y, Kysela B, Hanakahi LA, Manolis K, Riballo E, Stumm M, Harville TO, West SC, Oettinger MA, JeggoPA. Non-homologous end joining and V (D) J recombination require an additional factor. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5): 2462-7. PMID: 12604777
O’Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell 2001 Dec; 8(6):1175-85. PMID: 11779494
Riballo E, Doherty AJ, Dai Y, Stiff T, Oettinger MA, Jeggo PA, Kysela B. Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity. J Biol Chem. 2001 Aug 17; 276(33):31124-32. PMID: 11349135
Kim DR, Dai Y, Mundy CL, Yang W, Oettinger MA. Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase. Genes Dev. 1999 Dec.1;13(23):3070-80. PMID: 10601033
Former lab members
Technologies available for sharing upon request
Chromatin Immunoprecipitation (ChIPs)
Mouse xenograft tumor models