| The Johns Hopkins Family Professor in Oncology Research Professor of Medicine, Cell Biology, Oncology and Pathology Vice Dean for Research, School of Medicine Contact Information: |  |
Clinical/Academic Interests
Anemias, Bone Marrow Failure, Myeloproliferative Disorders
Research Interests
My laboratory is studying the mechanisms underlying the neoplastic activities of the MYC oncogene. MYC encodes a transcription factor, c-Myc, that heterodimerizes with Max to bind specific DNA sequences. We have contributed extensively to the identification of functional domains of the c-Myc protein. We, and others, have found that Myc/Max binds to E-box (CANNTG) sequences to activate transcription and other elements to suppress transcription. We have recently identified thousands putative c-Myc target genes using representational difference analysis and DNA microarray analysis. These genes are part of a growing list of putative c-Myc target genes that are estimated to involve about 10% of genes. We have begun to catalog these genes (www.myc-cancer-gene.org) and are using this database and exploiting phylogenetic footprinting (bioinformatics) to predict in vivo c-Myc binding sequences. The binding regions are validated by a technique we invented, Scanning Chromatin Immunoprecipitation (SChIP). We are currently defining the roles of five selected genes in Myc-mediated phenotypes. Our studies have led to the discovery that c-Myc overexpression activates genes encoding proteins involved in glycolysis and contributes to the Warburg effect or aerobic glycolysis, which is characteristic of essentially all solid tumors. We recently discovered a key role c-Myc in the regulation of mitochondrial homeostasis. In addition, we discovered that c-Myc overexpression contributes to genomic instability by uncoupling S and M phases of the cell cycle; this effect renders c-Myc overexpressing cycle sensitive to anti-mitotics. Our work and those of others have led to the concept that MYC is a central regulator of cell proliferation and cellular metabolism.
1972-1975 | University of Michigan, Ann Arbor, MI; B.S. chemistry (highest honors) |
1975-1978 | Georgetown University, Washington, D.C.; Ph.D. chemistry (distinction) |
1978-1982 | Johns Hopkins University School of Medicine, Baltimore, MD; M.D. (Alpha Omega Alpha) |
1982-1983 | Internship; Department of Medicine; Johns Hopkins Hospital |
1983-1985 | Residency; Department of Medicine; Johns Hopkins Hospital |
1985-1987 | Fellowship; Hematology-Oncology; Cancer Research Institute; UCSF |
| 1987-1991 | Assistant Professor of Medicine; Johns Hopkins University School of Medicine |
1990-1995 | Assistant Professor of Cell Biology & Anatomy, Assistant Professor of Oncology |
1991-1997 | Associate Professor of Medicine |
1993-2003 | Director, Division of Hematology |
1994-2000 | Deputy Director of Research, Department of Medicine |
1995- | Joint appointment Molecular Biology & Genetics |
1997- | Professor of Medicine, Oncology, Pathology; 2000- Professor of Cell Biology |
Selected Publications
- Gardner LB, Li Q, Park MS, Flanagan WM, Semenza GL, Dang CV. Hypoxia inhibits G1/S transition through regulation of p27 expression. J Biol Chem 2001, 276:7919-26.
- Dang CV. Runner’s Anemia. JAMA. 2001, 286:714-6.
- Chou WC, Hawkins AL, Barrett JF, Griffin CA, Dang CV. Arsenic Inhibits Transcription of Telomerase (hTERT): Implications for carcinogenesis and anti-tumor therapy. J Clin Invest, 2001, 108:1541-7.
- Prescott JE, Osthus RC, Lee LA, Lewis BC, Shim H, Barrett JF, Guo Q, Hawkins AL, Griffin CA, Dang CV: A Novel c-Myc Responsive Gene, JPO1, Participates in Neoplastic Transformation. J Biol Chem, 2001, 276:48276-84.
- Zeller, KI, Haggerty T, Barrett JF, Guo Q, Wonsey DR, Dang CV: Characterization of Nucleophosmin (B23) as a Myc Target by Scanning Chromatin Immunoprecipitation (SChIP). J Biol Chem, 2001, 276:48285-91.
- Wonsey DR, Zeller KI, Dang CV: The c-Myc target gene PRDX3 is required for mitochondrial homeostasis and neoplastic transformation. Proc Natl Acad Sci USA, 2002, 99:6649-6654.
- Haggerty TJ, Zeller KI, Osthus RC, Wonsey DR, Dang CV: A Strategy for Identifying Transcription Factor Binding Sites Reveals Two Classes of Genomic c-Myc Target Sites. Proc Natl Acad Sci USA, 2003, 100:5313-5318.
- Zeller KI, Jegga AG, Aronow BJ, O'Donnell KA, Dang CV: An integrated database of genes responsive to the Myc oncogenic transcription factor: identification of direct genomic targets. Genome Biol, 2003 http://genomebiology.com/2003/4/10/R69.
- Gardner LB, Li F, Yang X, Dang CV: Anoxic Fibroblasts Activate a Replication Arrest that is Bypassed with E1a. Mol Cell Biol, 2003, 23: 9032-9045.
- Chou WC, Jie C, Kenedy AA, Jones RJ, Trush MA, Dang CV. Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells Proc Natl Acad Sci USA 2004, 101: 4578-4583.
- Kim J-W, Zeller KI, Wang Y, Jegga AG, Aronow B, O’Donnell KA, Dang CV. Evaluation of Myc E-box Phylogenetic Footprints in Glycolytic Genes by Chromatin Immunoprecipitation Assays. Mol Cell Biol, 2004, 24:5923-5936.
- Chou WC, Chen HY, Yu SL, Cheng L, Yang PC, Dang CV. Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Mar 10; [Epub ahead of print].
- Barrett JF, Lee LA, Dang CV. Stimulation of Myc transactivation by the TATA binding protein in promoter-reporter assays. BMC Biochemistry 2005, 6:7 doi:10.1186/1471-2091-6-7.
- Osthus RC, Karim B, Prescott J, Smith BD, McDevitt M, Huso DL, Dang CV. The Myc Target Gene JPO1/CDCA7 is Frequently Over-expressed in Human Tumors and has Limited Transforming Activity In Vivo. Cancer Res, 2005, in press.
- O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT. C-Myc-regulated microRNAs modulate E2F1 expression. Nature, 2005, in press
- Li F, Wang Y, Zeller KI, Potter JJ, Wonsey DR, O’Donnell KA, Kim JW, Yustein JT, Lee LA, Dang CV. Myc stimulates nuclear encoded mitochondrial genes and mitochondrial biogenesis. Mol Cell Biol. 2005, in press.
