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Myles A. Brown, MD


Researcher

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Researcher

  • Physician
  • Director, Center for Functional Cancer Epigenetics
  • Emil Frei III Professor of Medicine, Harvard Medical School

Contact Information

  • Office Phone Number(617) 632-3948
  • Fax(617) 582-8501

Bio

Dr. Brown obtained his undergraduate degree in Biology from Yale University and his M.D. from the Johns Hopkins University School of Medicine. He completed training in Internal Medicine at the Brigham and Women's Hospital while doing research with David Livingston at the Dana-Farber. He went on to complete training in Medical Oncology at the Dana-Farber and postdoctoral research with Phillip Sharp at MIT. Following the completion of his training he joined the faculty of the Dana-Farber and Harvard Medical School. From 2002-2010 he served as Chief of the Division of Molecular and Cellular Oncology at the Dana-Farber. In 2010 together with Shirley Liu he founded the Center for Functional Cancer Epigenetics at the Dana-Farber.

Board Certification:

  • Internal Medicine, 1986
  • Medical Oncology, 1989

Fellowship:

  • Dana-Farber Cancer Institute, Medical Oncology
  • Massachusetts Institute Of Technology, Cancer Biology

Residency:

  • Brigham and Women's Hospital, Internal Medicine

Medical School:

  • Johns Hopkins University School of Medicine

Recent Awards:

  • American Society for Clinical Investigation 1997
  • Edwin B. Astwood Award, The Endocrine Society 2010
  • Tisch Family Outstanding Achievement Award, DFCI 2006
  • NAMS/Wyeth Pharmaceuticals SERM Research Award 2005
  • Elected to the Association of American Physicians 2003

Research

Epigenomics of hormone action

Dr. Brown’s research laboratory focuses on elucidating the epigenetic factors underlying the action of steroid hormones. This work has important implications both for normal physiology and for the treatment of hormone dependent malignancies including breast and prostate cancer. He is recognized for three seminal discoveries. His lab opened the steroid receptor coregulator field, illuminated the dynamic nature of receptor and coregulator interaction with the genome and elucidated the importance of epigenetically determined distant cis-regulatory steroid receptor binding sites. His contributions have uniquely reformulated the understanding of steroid hormone action in normal physiology and in hormone-dependent cancer.

FOXA1 upregulation promotes enhancer and transcriptional reprogramming in endocrine-resistant breast cancer. Proc Natl Acad Sci U S A. 2019 Dec 11.
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Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat Med. 2018 10; 24(10):1550-1558.
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Enhancing Therapy: It's about Time. Cell. 2018 08 09; 174(4):771-772.
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Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proc Natl Acad Sci U S A. 2017 06 27; 114(26):E5207-E5215.
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Embryonic transcription factor SOX9 drives breast cancer endocrine resistance. Proc Natl Acad Sci U S A. 2017 05 30; 114(22):E4482-E4491.
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TransCONFIRM: Identification of a Genetic Signature of Response to Fulvestrant in Advanced Hormone Receptor-Positive Breast Cancer. Clin Cancer Res. 2016 Dec 01; 22(23):5755-5764.
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SLCO2B1 and SLCO1B3 may determine time to progression for patients receiving androgen deprivation therapy for prostate cancer. J Clin Oncol. 2011 Jun 20; 29(18):2565-73.
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BINOCh: binding inference from nucleosome occupancy changes. Bioinformatics. 2011 Jul 01; 27(13):1867-8.
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PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B. Nat Cell Biol. 2011 Jun; 13(6):668-75.
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ß-Catenin is a useful adjunct immunohistochemical marker for the diagnosis of pulmonary lymphangioleiomyomatosis. Am J Clin Pathol. 2011 May; 135(5):776-82.
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Epigenetic switch involved in activation of pioneer factor FOXA1-dependent enhancers. Genome Res. 2011 Apr; 21(4):555-65.
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CaM kinase kinase beta-mediated activation of the growth regulatory kinase AMPK is required for androgen-dependent migration of prostate cancer cells. Cancer Res. 2011 Jan 15; 71(2):528-37.
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Differentiation-specific histone modifications reveal dynamic chromatin interactions and partners for the intestinal transcription factor CDX2. Dev Cell. 2010 Nov 16; 19(5):713-26.
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Genomic collaboration of estrogen receptor alpha and extracellular signal-regulated kinase 2 in regulating gene and proliferation programs. Mol Cell Biol. 2011 Jan; 31(1):226-36.
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Growth factor stimulation induces a distinct ER(alpha) cistrome underlying breast cancer endocrine resistance. Genes Dev. 2010 Oct 01; 24(19):2219-27.
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TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions. Proc Natl Acad Sci U S A. 2010 Aug 24; 107(34):15157-62.
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8q24 prostate, breast, and colon cancer risk loci show tissue-specific long-range interaction with MYC. Proc Natl Acad Sci U S A. 2010 May 25; 107(21):9742-6.
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Estrogen-dependent and estrogen-independent mechanisms contribute to AIB1-mediated tumor formation. Cancer Res. 2010 May 15; 70(10):4102-11.
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Subcellular localization of activated AKT in estrogen receptor- and progesterone receptor-expressing breast cancers: potential clinical implications. Am J Pathol. 2010 May; 176(5):2139-49.
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Nucleosome dynamics define transcriptional enhancers. Nat Genet. 2010 Apr; 42(4):343-7.
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MYC regulation of a "poor-prognosis" metastatic cancer cell state. Proc Natl Acad Sci U S A. 2010 Feb 23; 107(8):3698-703.
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Multimodal regulation of E2F1 gene expression by progestins. Mol Cell Biol. 2010 Apr; 30(8):1866-77.
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Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase. Cancer Cell. 2009 Nov 06; 16(5):413-24.
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Elucidation of the ELK1 target gene network reveals a role in the coordinate regulation of core components of the gene regulation machinery. Genome Res. 2009 Nov; 19(11):1963-73.
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Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer. Cell. 2009 Jul 23; 138(2):245-56.
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Estradiol-regulated microRNAs control estradiol response in breast cancer cells. Nucleic Acids Res. 2009 Aug; 37(14):4850-61.
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FOXA1 is a potential oncogene in anaplastic thyroid carcinoma. Clin Cancer Res. 2009 Jun 01; 15(11):3680-9.
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Induction of Kruppel-like factor 5 expression by androgens results in increased CXCR4-dependent migration of prostate cancer cells in vitro. Mol Endocrinol. 2009 Sep; 23(9):1385-96.
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Cistromics of hormone-dependent cancer. Endocr Relat Cancer. 2009 Jun; 16(2):381-9.
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Coactivator function defines the active estrogen receptor alpha cistrome. Mol Cell Biol. 2009 Jun; 29(12):3413-23.
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The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines. Cancer Res. 2009 Apr 15; 69(8):3356-63.
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Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells. Cancer Res. 2009 Apr 01; 69(7):3140-7.
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Integrative analysis of HIF binding and transactivation reveals its role in maintaining histone methylation homeostasis. Proc Natl Acad Sci U S A. 2009 Mar 17; 106(11):4260-5.
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Cell-type selective chromatin remodeling defines the active subset of FOXA1-bound enhancers. Genome Res. 2009 Mar; 19(3):372-80.
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Combining chromatin immunoprecipitation and oligonucleotide tiling arrays (ChIP-Chip) for functional genomic studies. Methods Mol Biol. 2009; 556:155-64.
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Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature. 2008 Dec 04; 456(7222):663-6.
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AKT alters genome-wide estrogen receptor alpha binding and impacts estrogen signaling in breast cancer. Mol Cell Biol. 2008 Dec; 28(24):7487-503.
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Unique ERalpha cistromes control cell type-specific gene regulation. Mol Endocrinol. 2008 Nov; 22(11):2393-406.
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Model-based analysis of ChIP-Seq (MACS). Genome Biol. 2008; 9(9):R137.
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Androgen receptor mediates the expression of UDP-glucuronosyltransferase 2 B15 and B17 genes. Prostate. 2008 Jun 01; 68(8):839-48.
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Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer. J Natl Cancer Inst. 2008 Jun 04; 100(11):815-25.
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CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization. Cancer Res. 2008 May 01; 68(9):3204-13.
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FoxA1 translates epigenetic signatures into enhancer-driven lineage-specific transcription. Cell. 2008 Mar 21; 132(6):958-70.
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Targeting NF-kappaB in Waldenstrom macroglobulinemia. Blood. 2008 May 15; 111(10):5068-77.
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Unraveling estrogen action in osteoporosis. . 2008 May 15; 7(10):1348-52.
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Estrogen protects bone by inducing Fas ligand in osteoblasts to regulate osteoclast survival. EMBO J. 2008 Feb 06; 27(3):535-45.
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xMAN: extreme MApping of OligoNucleotides. BMC Genomics. 2008; 9 Suppl 1:S20.
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CARM1 regulates estrogen-stimulated breast cancer growth through up-regulation of E2F1. Cancer Res. 2008 Jan 01; 68(1):301-6.
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A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth. Mol Cell. 2007 Aug 03; 27(3):380-92.
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Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer. Cancer Res. 2007 Jul 01; 67(13):6477-83.
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Targeting the AIB1 oncogene through mammalian target of rapamycin inhibition in the mammary gland. Cancer Res. 2006 Dec 01; 66(23):11381-8.
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Genome-wide analysis of estrogen receptor binding sites. Nat Genet. 2006 Nov; 38(11):1289-97.
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A cell-type-specific transcriptional network required for estrogen regulation of cyclin D1 and cell cycle progression in breast cancer. Genes Dev. 2006 Sep 15; 20(18):2513-26.
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Model-based analysis of tiling-arrays for ChIP-chip. Proc Natl Acad Sci U S A. 2006 Aug 15; 103(33):12457-62.
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p63 regulates an adhesion programme and cell survival in epithelial cells. Nat Cell Biol. 2006 Jun; 8(6):551-61.
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X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell. 2006 Feb; 9(2):121-32.
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Proceedings of the Fifth International Conference on Recent Advances and Future Directions in Endocrine Therapy for Breast Cancer: conference summary statement. Clin Cancer Res. 2006 Feb 01; 12(3 Pt 2):997s-1000s.
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Estrogen receptor target gene: an evolving concept. Mol Endocrinol. 2006 Aug; 20(8):1707-14.
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Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Mol Cell. 2005 Sep 02; 19(5):631-42.
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Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell. 2005 Jul 15; 122(1):33-43.
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Androgen mediated regulation and functional implications of fkbp51 expression in prostate cancer. J Urol. 2005 May; 173(5):1772-7.
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Cell cycle progression stimulated by tamoxifen-bound estrogen receptor-alpha and promoter-specific effects in breast cancer cells deficient in N-CoR and SMRT. Mol Endocrinol. 2005 Jun; 19(6):1543-54.
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High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene. Cancer Cell. 2004 Sep; 6(3):263-74.
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Coactivator AIB1 links estrogen receptor transcriptional activity and stability. Proc Natl Acad Sci U S A. 2004 Aug 10; 101(32):11599-604.
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Proceedings of the Third International Conference on Recent Advances and Future Directions in Endocrine Manipulation of Breast Cancer: conference summary statement. Clin Cancer Res. 2004 Jan 01; 10(1 Pt 2):327S-330S.
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Advances in estrogen receptor biology: prospects for improvements in targeted breast cancer therapy. Breast Cancer Res. 2004; 6(1):39-52.
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Agonist and chemopreventative ligands induce differential transcriptional cofactor recruitment by aryl hydrocarbon receptor. Mol Cell Biol. 2003 Nov; 23(21):7920-5.
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Coregulator expression and breast cancer: improving the predictive power of estrogen receptor alpha. Clin Cancer Res. 2003 Apr; 9(4):1229-30.
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Overview consensus statement. Newer approaches to androgen deprivation therapy in prostate cancer. Urology. 2002 Sep; 60(3 Suppl 1):1-6.
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ERAP140, a conserved tissue-specific nuclear receptor coactivator. Mol Cell Biol. 2002 May; 22(10):3358-72.
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Molecular determinants for the tissue specificity of SERMs. Science. 2002 Mar 29; 295(5564):2465-8.
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Formation of the androgen receptor transcription complex. Mol Cell. 2002 Mar; 9(3):601-10.
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The androgen receptor CAG repeat polymorphism and risk of breast cancer in the Nurses' Health Study. Cancer Res. 2002 Feb 15; 62(4):1045-9.
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No association between a single nucleotide polymorphism in CYP19 and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2002 Feb; 11(2):215-6.
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Growth factor requirements and basal phenotype of an immortalized mammary epithelial cell line. Cancer Res. 2002 Jan 01; 62(1):89-98.
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