| Email |
kburns@jhmi.edu |
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(410) 502-7214 |
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Kathleen H. Burns, M.D., Ph.D.
Primary Appointment in Pathology; Secondary Appointment in Oncology
Member, Graduate Program in Pathobiology
My laboratory studies roles of transposable elements in human cancers, with an emphasis on the hematopoietic neoplasias. There is compelling evidence that these poorly understood mobile DNAs have potential to contribute to genomic instability and mRNA transcript alterations in the context of neoplasia, and we believe inherited insertions also may create predispositions to disease.
Projects in the lab include:
(i.) The development of one-sided PCR based assays to map transposon insertions in the human genome;
(ii.) Finding evidence for somatic insertions of mobilized DNAs in cancers, and exploring potential clinical markers for this instability;
(iii.) Describing common inherited transposon insertion polymorphisms in cancer patients and assessing whether these structural variations contribute to cancer susceptibility or tumor progression.
Publications
GASZ is essential for male meiosis and suppression of retrotransposon expression in the male germline.
Ma L, Buchold GM, Greenbaum MP, Roy A, Burns KH, Zhu H, Han DY, Harris RA, Coarfa C, Gunaratne PH, Yan W, Matzuk MM.
PLoS Genet. 2009 Sep;5(9):e1000635
A descent into the nuage: the maelstrom of transposon control.
O'Donnell KA, Burns KH, Boeke JD.
Dev Cell. 2008 Aug;15(2):179-81.
Great exaptations.
Burns KH, Boeke JD.
J Biol. 2008;7(2):5.
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| Email |
cvdang@jhmi.edu |
| Phone |
(410) 955-7873 |
Related Websites
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MYC cancer gene
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Chi V. Dang, M.D., Ph.D.
Vice Dean for Research, School of Medicine
Primary Appointment in Medicine; Secondary Appointments in Pathology, Oncology, and Cell Biology; Joint Appointment in Molecular Biology and Genetics
Member, Graduate Program in Cellular and Molecular Medicine; Member, Graduate Program in Human Genetics
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 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. We are also dissecting the hypoxia induced G1-S checkpoint and have discovered a novel hypoxia inducible signaling pathway. Our characterization of a hypoxia inducible G1 checkpoint through p27 has further extended our understanding of how neoplastic cells may circumvent hypoxia induced growth arrest. On the other hand this mechanism may also be exploited to trigger arrested cells to undergo replication in hypoxia, thereby making them susceptible to radiation or chemotherapy.
Publications
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;4(10):R69. 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, ODonnell KA, Dang CV. Evaluation of Myc E-box Phylogenetic Footprints in Glycolytic Genes by Chromatin Immunoprecipitation Assays. Mol Cell Biol, 2004, 24:5923-5936. |
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| Email |
tkickler@jhmi.edu |
| Phone |
(410) 955-6315 |
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Thomas S. Kickler, M.D.
Primary Appointment in Pathology; Secondary Appointments in Medicine and Oncology
We study the role of platelets in bleeding, thrombosis, and inflammation.
Publications
Brotman D, Segal J, Petty B, Kickler TS. Limitations of D-dimer testing in patients with suspected of venous thromboembolism. American J of Medicine 114:276-282, 2003
Kickler TS. Mechanism of Anti-D in Autoimmune thrombocytopenia. Blood 102 2713, 2003
Campbell S, Shirey RS, Kickler TS. Neonatal alloimmune thrombocytopenia due to anti HPA 5b. Immunohematology 19:127-132, 2003
Williams MS, Kim, SY, Herr M, Kickler T, and P Ouyang. Long-term hormone replacement therapy does not cause increased platelet activation. Journal of Investigative Medicine 51:S379, 2003.
Streiff M, Weir E, Segal J, Kickler TS, Grossman S. ABO blood group is a potent risk factor for venous thromboembolism in patients with malignant gliomas.Cancer. 2004 Apr 15;100(8):1717-23. |
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| Email |
mstreif@jhmi.edu |
| Phone |
(410) 614-0727 |
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Michael B. Streiff, M.D.
Primary Appointment in Medicine; Secondary Appointment in Pathology
As a hematologist, I am primarily interested in disorders of thrombosis and hemostasis. Consequently, my research focuses on the clinical and laboratory investigation of coagulation disorders, with a particular emphasis on the application of novel laboratory assays to explore the pathogenesis and treatment of thrombophilic disorders.
Publications
Streiff, M.B. Vena Caval Filters: A Comprehensive Review. Blood 2000; 95:3669-3677.
Arai S. Allan C, Streiff M, Hutchins GM Vogelsang GB, Tsai H-M. VonWillebrand factor-cleaving protease activity and proteolysis of vonWillebrand factor in bone marrow transplant-associated thromboticmicroangiopathy. Hematol J 2001; 2:292-299.
Streiff MB, Spivak JL. The diagnosis and management of polycythemia verain the post-polycythemia vera study group era: A survey of American Societyof Hematology (ASH) members' practice patterns. Blood 2002; 99:1144-1149.
Streiff MB, Ness PM. Acquired factor V inhibitors: a needless iatrogeniccomplication of bovine thrombin exposure. Transfusion 2002 ;42: 18-26.
Streiff MB, Mehta S, Thomas DL. Peripheral blood count abnormalities amongpersons with hepatitis C in the United States. Hepatology 2002; 35:947-952. |
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| Email |
mvuica@jhmi.edu |
| Phone |
(410) 554-1225 |
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Milena Vuica-Ross, M.D.
Primary Appointment in Pathology
Cancer progression is often associated with the accumulation of gross chromosomal rearrangements (GCRs), such as translocations, deletion of a chromosome arm, internal deletions or inversions. These malignancies are generally unresponsive to treatment and carry dismal prognoses. Not much is known about the processes that lead to genome rearrangements, what pathways might suppress rearrangements, and whether defects in these pathways underlie the ongoing genome instability seen in many cancers. This highlights a need for better understanding of the underlying biology, which hopefully will lead to better management of these malignancies.
Recent studies in yeast Saccharomyces cerevisiae have begun to uncover extensive and redundant pathways and genes that keep the rate of chromosomal rearrangements at very low levels. Human homologous of several of these genes have well-established roles as tumor suppressors, consistent with the hypothesis that the mechanisms preserving genomic stability in yeast are the same ones that go awry in cancer. To look for the factors that prevent a loss of a chromosome arm (q- phenotype), we have developed a genome wide screen for terminal deletions in a yeast artificial chromosome (YAC) carrying human chromosome VII sequence flanked by several selectable markers. The YAC has been transferred into an isogenic set of yeast deletion mutants from the recently completed Yeast Genome Deletion Project. We have identified potentially novel chromosome integrity determinants and are currently characterizing them.
Publications
Banfic H, Vuica M, Knotek M, Moslavac S, Divecha N. Inositol lipid signalling occurs
in brush-border membranes during initiation of compensatory renal growth in the rat. Biochem
J. 1993, 295:599-605.
Vuica M, Desiderio S, Schneck JP. Differential effects of B cell receptor and B cell receptor-Fc?RIIB1 engagement on docking of Csk to GAP-associated p62. J Exp Med 1997, 186:259-267.
Casteel DE, Zhuang S, Gudi T, Tang J, Vuica M, Desiderio S, Piltz R. cGMP-dependent protein kinase I beta physically and functionally interacts with the transcriptional regulator TFII-I. J Biol Chem 2002, 277:32003-32014.
Ross AE, Vuica M, Desiderio S. Overlapping signals for protein degradation and nuclear localization define a role for intrinsic RAG-2 nuclear uptake in dividing cells. Mol Cell Biol. 2003, 5308-5319.
Campbell JL, Maringele L, Vuica M, Lydall D, Cohen-Fix O. Absence of the mlp1 and mlp2 proteins leads to DNA damage and altered telomere length maintenance. Submitted. |
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