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  • Duke University Center for Microbial Pathogenesis
    atypical pneumonias Within infected cells Chlamydia resides in a large membrane bound vacuole termed an inclusion The inclusion is largely segregated from classical endocytic and exocytic membrane transport pathways and yet is able to efficiently acquire nutrients and lipids from the host The vital role of cytoskeletal networks in maintenance of intracellular organelle position as well as membrane protein and lipid traffic prompted us to examine the arrangement of the host cytoskeleton in infected cells Here we report a dynamic interaction between inclusions and the host cytoskeletal elements We have determined that the inclusion is encased by a network of actin and intermediate filaments IF IFs are one of the major cytoskeletal components of metazoans and mostly play a role in maintaining cell shape and motility Surprisingly cytoplasmic IF proteins encasing the inclusions vimentin cytokeratin 8 and cytokeratin 18 were proteolytically processed during infection We determined that a chlamydial secreted protease CPAF was responsible for cleavage of these proteins and mapped the cleavage site to the N terminal head region a domain required for filament formation Remarkably despite removal of the Head domain both vimentin and keratin filaments were retained as a filamentous cage enveloping the inclusion Upon treatment with detergents bacteria within the inclusions remained intact suggesting that the IF cage provides structural integrity to the inclusion Indeed inclusions formed in MEFs from vimentin knockout mice were sensitive to detergent extraction and accumulated inclusion membrane derived fibers presumably the remnants of damaged inclusion membranes Finally maintenance of the vimentin cage around the inclusion required an intact actin filament network since disruption of actin led to loss of the vimentin cage hyper fibrillation of the inclusion membrane and disintegration of the inclusion Our results provide evidence for a novel pathogenic strategy wherein Chlamydiae proteolytically processes and re organizes the IF

    Original URL path: http://mgm.duke.edu/microbial/training/awards_2.htm (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    Department of Biology Over the past 30 years at the University of Toronto Stanford University Case Western Reserve University and now Duke University we have been engaged in projects exploring complex genome sequences their evolution their packaging in various types of chromatin and their effects on diverse phenomena such as centromere function dosage compensation and gene function in genomes ranging from human to other primates and mammals to yeast In

    Original URL path: http://mgm.duke.edu/faculty/willard/index.htm (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    919 681 5055 Fax 919 684 8902 Email gary cox duke edu biography lab members publications website My lab is using Cryptococcus neoformans as a model human pathogenic fungus to gain insights into the pathogenesis of fungal infections The ultimate hope is to translate these insights into improvements in the diagnosis and treatment of fungal diseases in humans The lab has focused on two main areas high temperature growth and

    Original URL path: http://mgm.duke.edu/microbial/mycology/cox/ (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    of protecting persons with HIV infection from opportunistic infections and malignancies Since HIV infection leads to progressive CD4 loss we direct our vaccines toward the induction of memory CD8 cells We developed a murine model for Mycobacterium avium infection This bacterium is related to M tuberculosis and is a common cause of disseminated infections in AIDS patients Two DNA vaccines which we developed provide partial protection in the mouse model

    Original URL path: http://mgm.duke.edu/microbial/bacteriology/frothingham/ (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    one of the deadliest of human viruses and cowpox virus the virus that Edward Jenner used to begin the eradication of smallpox One of the especially interesting features of theses viruses is their ability to interfere with a wide range of innate and adaptive immune responses to infection For example we have found that cowpox virus inhibits inflammation by suppressing the actions of cytokines controlling inflammatory processes Moreover the virus does this in several ways by preventing the synthesis of cytokines by interfering with normal cytokine receptor interactions and by inhibiting cytokine signaling pathways Our main research objectives are to identify mechanisms of virus host interaction leading to the modification or alteration of host functions Our working model is that such interactions are amongst the most important factors in viral pathogenesis In addition knowledge of these virus host interactions should help in the development of new vaccines and therapies for a variety of conditions associated with infectious diseases inflammatory diseases autoimmune diseases cancers and organ transplantation Development of improved viral vaccines Several excellent vaccine platforms exist but among these vaccinia virus vaccines have unusual potential for targeting multiple different pathogens because of the extraordinary capacity of these vectors to encode

    Original URL path: http://mgm.duke.edu/faculty/pickup/index.htm (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    have focused on a family of proteins known as Immunity Related GTPases IRG also known as p47 GTPases which have been associated with both Crohn s disease and resistance to mycobacterial infections in humans We were among the first to clone IRG genes in the mouse and to define their biochemical activity cellular localization and cellular functions prominent among which is regulation of autophagy By generating mice that lack certain

    Original URL path: http://mgm.duke.edu/microbial/bacteriology/taylor/ (2014-06-13)
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  • Duke University Center for Microbial Pathogenesis
    is suppressed by the colonic biota and were able to simulate suppression in gnotobiotic mice by colonizing them with a complex collection of bacteria isolated from the normal mouse cecum It was also possible to show that normal bacteria suppressed C difficile by competing more efficiently for carbohydrates found in the gut Work with C difficile continues with a small collection of fastidious organisms from human biota that exert a

    Original URL path: http://mgm.duke.edu/microbial/bacteriology/wilson/ (2014-06-13)
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  • Duke University Department of Molecular Genetics & Microbiology
    Ellis MJ Dressman HK Bentley RC Baker JA Marcom PK Nevins JR Marks JR Olson JA Breast Cancer Res Treat 2009 Dec 118 3 635 43 Abstract Balancing the decision of cell proliferation and cell fate Hallstrom TC Nevins JR Cell Cycle 2009 Feb 15 8 4 532 5 Abstract Genomic and molecular profiling predicts response to temozolomide in melanoma Augustine CK Yoo JS Potti A Yoshimoto Y Zipfel PA Friedman HS Nevins JR Ali Osman F Tyler DS Clin Cancer Res 2009 Jan 15 15 2 502 10 Abstract The genomic analysis of lactic acidosis and acidosis response in human cancers Chen JL Lucas JE Schroeder T Mori S Wu J Nevins J Dewhirst M West M Chi JT PLoS Genet 2008 Dec 4 12 e1000293 Abstract High Dimensional Sparse Factor Modeling Applications in Gene Expression Genomics Carvalho CM Chang J Lucas JE Nevins JR Wang Q West M J Am Stat Assoc 2008 Dec 1 103 484 1438 1456 Abstract Utilization of pathway signatures to reveal distinct types of B lymphoma in the Emicro myc model and human diffuse large B cell lymphoma Mori S Rempel RE Chang JT Yao G Lagoo AS Potti A Bild A Nevins JR Cancer Res 2008 Oct 15 68 20 8525 34 Abstract A genomic approach to identify molecular pathways associated with chemotherapy resistance Riedel RF Porrello A Pontzer E Chenette EJ Hsu DS Balakumaran B Potti A Nevins J Febbo PG Mol Cancer Ther 2008 Oct 7 10 3141 9 Abstract Toward the individualization of lung cancer therapy Anguiano A Nevins JR Potti A Cancer 2008 Oct 1 113 7 Suppl 1760 7 Abstract Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression Anders CK Hsu DS Broadwater G Acharya CR Foekens JA Zhang Y Wang Y Marcom PK Marks JR Febbo PG Nevins JR Potti A Blackwell KL J Clin Oncol 2008 Jul 10 26 20 3324 30 Abstract Patterns of cell signaling pathway activation that characterize mammary development Andrechek ER Mori S Rempel RE Chang JT Nevins JR Development 2008 Aug 135 14 2403 13 Abstract Sensing and integration of Erk and PI3K signals by Myc Lee T Yao G Nevins J You L PLoS Comput Biol 2008 Feb 4 2 e1000013 Abstract An integrative approach to characterize disease specific pathways and their coordination a case study in cancer Xu M Kao MC Nunez Iglesias J Nevins JR West M Zhou XJ BMC Genomics 2008 9 Suppl 1 S12 Abstract Gene expression signatures of radiation response are specific durable and accurate in mice and humans Meadows SK Dressman HK Muramoto GG Himburg H Salter A Wei Z Ginsburg GS Ginsburg G Chao NJ Nevins JR Chute JP PLoS One 2008 3 4 e1912 Abstract A bistable Rb E2F switch underlies the restriction point Yao G Lee TJ Mori S Nevins JR You L Nat Cell Biol 2008 Apr 10 4 476 82 Abstract A role for Myc in facilitating transcription activation by E2F1 Leung JY Ehmann GL Giangrande PH Nevins JR Oncogene 2008 Jul 10 27 30 4172 9 Abstract Age specific differences in oncogenic pathway deregulation seen in human breast tumors Anders CK Acharya CR Hsu DS Broadwater G Garman K Foekens JA Zhang Y Wang Y Marcom K Marks JR Mukherjee S Nevins JR Blackwell KL Potti A PLoS One 2008 3 1 e1373 Abstract An E2F1 dependent gene expression program that determines the balance between proliferation and cell death Hallstrom TC Mori S Nevins JR Cancer Cell 2008 Jan 13 1 11 22 Abstract New breast cancer genes discovery at the intersection of complex data sets Nevins JR Cancer Cell 2007 Dec 12 6 497 9 Abstract Phylogenetic simulation of promoter evolution estimation and modeling of binding site turnover events and assessment of their impact on alignment tools Huang W Nevins JR Ohler U Genome Biol 2007 8 10 R225 Abstract Genomic strategies for personalized cancer therapy Garman KS Nevins JR Potti A Hum Mol Genet 2007 Oct 15 16 Spec No 2 R226 32 Abstract Distinct roles of E2F proteins in vascular smooth muscle cell proliferation and intimal hyperplasia Giangrande PH Zhang J Tanner A Eckhart AD Rempel RE Andrechek ER Layzer JM Keys JR Hagen PO Nevins JR Koch WJ Sullenger BA Proc Natl Acad Sci U S A 2007 Aug 7 104 32 12988 93 Abstract Mining gene expression profiles expression signatures as cancer phenotypes Nevins JR Potti A Nat Rev Genet 2007 Aug 8 8 601 9 Abstract Gene expression signatures that predict radiation exposure in mice and humans Dressman HK Muramoto GG Chao NJ Meadows S Marshall D Ginsburg GS Nevins JR Chute JP PLoS Med 2007 Apr 4 4 e106 Abstract Identification of genes associated with ovarian cancer metastasis using microarray expression analysis Lancaster JM Dressman HK Clarke JP Sayer RA Martino MA Cragun JM Henriott AH Gray J Sutphen R Elahi A Whitaker RS West M Marks JR Nevins JR Berchuck A Int J Gynecol Cancer 2006 Sep Oct 16 5 1733 45 Abstract Genomic prediction of locoregional recurrence after mastectomy in breast cancer Cheng SH Horng CF West M Huang E Pittman J Tsou MH Dressman H Chen CM Tsai SY Jian JJ Liu MC Nevins JR Huang AT J Clin Oncol 2006 Oct 1 24 28 4594 602 Abstract GATHER a systems approach to interpreting genomic signatures Chang JT Nevins JR Bioinformatics 2006 Dec 1 22 23 2926 33 Abstract Linking oncogenic pathways with therapeutic opportunities Bild AH Potti A Nevins JR Nat Rev Cancer 2006 Sep 6 9 735 41 Abstract Compensation and specificity of function within the E2F family Kong LJ Chang JT Bild AH Nevins JR Oncogene 2007 Jan 18 26 3 321 7 Abstract Embracing the complexity of genomic data for personalized medicine West M Ginsburg GS Huang AT Nevins JR Genome Res 2006 May 16 5 559 66 Abstract The Rb related p130 protein controls telomere lengthening through an interaction

    Original URL path: http://mgm.duke.edu/faculty/nevins/pubs.htm (2014-06-13)
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