Sarah Merritt Fortune, M.D.
| Title | Melvin J. and Geraldine L. Glimcher Assiocate Professor of Immunology and Infectious Diseases |
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| Institution | Harvard School of Public Health |
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| Department | Immunology and Infectious Diseases |
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| Address | Harvard School of Public Health Bldg 1-Room 809, Immunology and Infectious Diseases 665 Huntington Ave Boston MA 02115
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| Phone | 617/432-6965 |
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| Fax | 617/432-3259 |
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Mentoring Available: 09/01/13, Expires: 06/01/14 This is a medical research fellowship funded by the Doris Duke Clinical Foundation.
Mycobacterium tuberculosis remains an enormous global health problem. One of the challenges in controlling tuberculosis is the wide spectrum of disease that follows M. tuberculosis infection. It is estimated that over a third of the world’s population is latently infected with M. tuberculosis yet only 10% of these individuals will ever develop clinical disease. When disease occurs, it may be localized or metastatic, rapidly progressive or indolent. There are similarly variable outcomes in response to treatment. It is currently unclear to what extent the variable clinical outcomes reflect differences in the infected individuals’ ability to control the disease versus diversity in the bacterial responses during infection.
The Fortune lab seeks to define the mechanisms by which populations of M. tuberculosis generate functional diversity and determine how this diversification contributes to the variable course of clinical disease. We approach these questions using bacterial genetics, high throughput genomic and microfluidic based live cell imaging approaches. We have recently demonstrated that mycobacterial cells grow and divide asymmetrically. This pattern of asymmetric growth and division creates cells that are differentially susceptible to antibiotics. Current studies in the lab seek to define the molecular basis of asymmetric growth and division and the molecular basis of replicative fidelity. Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications.
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Chao MC, Kieser KJ, Minami S, Mavrici D, Aldridge BB, Fortune SM, Alber T, Rubin EJ. Protein Complexes and Proteolytic Activation of the Cell Wall Hydrolase RipA Regulate Septal Resolution in Mycobacteria. PLoS Pathog. 2013 Feb; 9(2):e1003197.
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De Leon J, Jiang G, Ma Y, Rubin E, Fortune S, Sun J. Mycobacterium tuberculosis ESAT-6 Exhibits a Unique Membrane-interacting Activity That Is Not Found in Its Ortholog from Non-pathogenic Mycobacterium smegmatis. J Biol Chem. 2012 Dec 28; 287(53):44184-91.
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Fortune SM. The Surprising Diversity of Mycobacterium tuberculosis: Change You Can Believe In. J Infect Dis. 2012 Dec; 206(11):1642-4.
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Martin CJ, Booty MG, Rosebrock TR, Nunes-Alves C, Desjardins DM, Keren I, Fortune SM, Remold HG, Behar SM. Efferocytosis is an innate antibacterial mechanism. Cell Host Microbe. 2012 Sep 13; 12(3):289-300.
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Lee HJ, Lang PT, Fortune SM, Sassetti CM, Alber T. Cyclic AMP regulation of protein lysine acetylation in Mycobacterium tuberculosis. Nat Struct Mol Biol. 2012 Aug; 19(8):811-8.
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Wirth SE, Krywy JA, Aldridge BB, Fortune SM, Fernandez-Suarez M, Gray TA, Derbyshire KM. Polar assembly and scaffolding proteins of the virulence-associated ESX-1 secretory apparatus in mycobacteria. Mol Microbiol. 2012 Feb; 83(3):654-64.
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Ford C, Yusim K, Ioerger T, Feng S, Chase M, Greene M, Korber B, Fortune S. Mycobacterium tuberculosis - Heterogeneity revealed through whole genome sequencing. Tuberculosis (Edinb). 2012 May; 92(3):194-201.
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Aldridge BB, Fernandez-Suarez M, Heller D, Ambravaneswaran V, Irimia D, Toner M, Fortune SM. Asymmetry and aging of mycobacterial cells lead to variable growth and antibiotic susceptibility. Science. 2012 Jan 6; 335(6064):100-4.
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Liong M, Fernandez-Suarez M, Issadore D, Min C, Tassa C, Reiner T, Fortune SM, Toner M, Lee H, Weissleder R. Specific pathogen detection using bioorthogonal chemistry and diagnostic magnetic resonance. Bioconjug Chem. 2011 Dec 21; 22(12):2390-4.
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Sillé FC, Martin C, Jayaraman P, Rothchild A, Fortune S, Besra GS, Behar SM, Boes M. Requirement for invariant chain in macrophages for Mycobacterium tuberculosis replication and CD1d antigen presentation. Infect Immun. 2011 Aug; 79(8):3053-63.
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Ford CB, Lin PL, Chase MR, Shah RR, Iartchouk O, Galagan J, Mohaideen N, Ioerger TR, Sacchettini JC, Lipsitch M, Flynn JL, Fortune SM. Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat Genet. 2011 May; 43(5):482-6.
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Millington KA, Fortune SM, Low J, Garces A, Hingley-Wilson SM, Wickremasinghe M, Kon OM, Lalvani A. Rv3615c is a highly immunodominant RD1 (Region of Difference 1)-dependent secreted antigen specific for Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A. 2011 Apr 5; 108(14):5730-5.
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Woodworth JS, Shin D, Volman M, Nunes-Alves C, Fortune SM, Behar SM. Mycobacterium tuberculosis directs immunofocusing of CD8+ T cell responses despite vaccination. J Immunol. 2011 Feb 1; 186(3):1627-37.
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Fortune SM, Rubin EJ. Host transcription in active and latent tuberculosis. Genome Biol. 2010; 11(9):135.
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Garces A, Atmakuri K, Chase MR, Woodworth JS, Krastins B, Rothchild AC, Ramsdell TL, Lopez MF, Behar SM, Sarracino DA, Fortune SM. EspA acts as a critical mediator of ESX1-dependent virulence in Mycobacterium tuberculosis by affecting bacterial cell wall integrity. PLoS Pathog. 2010; 6(6):e1000957.
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Ioerger TR, Feng Y, Ganesula K, Chen X, Dobos KM, Fortune S, Jacobs WR, Mizrahi V, Parish T, Rubin E, Sassetti C, Sacchettini JC. Variation among genome sequences of H37Rv strains of Mycobacterium tuberculosis from multiple laboratories. J Bacteriol. 2010 Jul; 192(14):3645-53.
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Bitter W, Houben EN, Bottai D, Brodin P, Brown EJ, Cox JS, Derbyshire K, Fortune SM, Gao LY, Liu J, Gey van Pittius NC, Pym AS, Rubin EJ, Sherman DR, Cole ST, Brosch R. Systematic genetic nomenclature for type VII secretion systems. PLoS Pathog. 2009 Oct; 5(10):e1000507.
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Siegrist MS, Unnikrishnan M, McConnell MJ, Borowsky M, Cheng TY, Siddiqi N, Fortune SM, Moody DB, Rubin EJ. Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition. Proc Natl Acad Sci U S A. 2009 Nov 3; 106(44):18792-7.
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Pandey AK, Yang Y, Jiang Z, Fortune SM, Coulombe F, Behr MA, Fitzgerald KA, Sassetti CM, Kelliher MA. NOD2, RIP2 and IRF5 play a critical role in the type I interferon response to Mycobacterium tuberculosis. PLoS Pathog. 2009 Jul; 5(7):e1000500.
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Divangahi M, Chen M, Gan H, Desjardins D, Hickman TT, Lee DM, Fortune S, Behar SM, Remold HG. Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair. Nat Immunol. 2009 Aug; 10(8):899-906.
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Atmakuri K, Fortune SM. Regulation of protein secretion by ... protein secretion? Cell Host Microbe. 2008 Sep 11; 4(3):190-1.
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Woodworth JS, Fortune SM, Behar SM. Bacterial protein secretion is required for priming of CD8+ T cells specific for the Mycobacterium tuberculosis antigen CFP10. Infect Immun. 2008 Sep; 76(9):4199-205.
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Hett EC, Chao MC, Steyn AJ, Fortune SM, Deng LL, Rubin EJ. A partner for the resuscitation-promoting factors of Mycobacterium tuberculosis. Mol Microbiol. 2007 Nov; 66(3):658-68.
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Fortune SM, Rubin EJ. The complex relationship between mycobacteria and macrophages: it's not all bliss. Cell Host Microbe. 2007 Jul 12; 2(1):5-6.
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Joshi SM, Pandey AK, Capite N, Fortune SM, Rubin EJ, Sassetti CM. Characterization of mycobacterial virulence genes through genetic interaction mapping. Proc Natl Acad Sci U S A. 2006 Aug 1; 103(31):11760-5.
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Fortune SM, Chase MR, Rubin EJ. Dividing oceans into pools: strategies for the global analysis of bacterial genes. Microbes Infect. 2006 May; 8(6):1631-6.
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Fortune SM, Jaeger A, Sarracino DA, Chase MR, Sassetti CM, Sherman DR, Bloom BR, Rubin EJ. Mutually dependent secretion of proteins required for mycobacterial virulence. Proc Natl Acad Sci U S A. 2005 Jul 26; 102(30):10676-81.
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Fortune SM, Solache A, Jaeger A, Hill PJ, Belisle JT, Bloom BR, Rubin EJ, Ernst JD. Mycobacterium tuberculosis inhibits macrophage responses to IFN-gamma through myeloid differentiation factor 88-dependent and -independent mechanisms. J Immunol. 2004 May 15; 172(10):6272-80.
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Fortune SM, Kaelin CM, Gulizia JM, Daily JP. Cat scratch disease presenting as a breast mass. Obstet Gynecol. 2000 Jun; 95(6 Pt 2):1027.
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Cleary AM, Fortune SM, Yellin MJ, Chess L, Lederman S. Opposing roles of CD95 (Fas/APO-1) and CD40 in the death and rescue of human low density tonsillar B cells. J Immunol. 1995 Oct 1; 155(7):3329-37.
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Yellin MJ, Winikoff S, Fortune SM, Baum D, Crow MK, Lederman S, Chess L. Ligation of CD40 on fibroblasts induces CD54 (ICAM-1) and CD106 (VCAM-1) up-regulation and IL-6 production and proliferation. J Leukoc Biol. 1995 Aug; 58(2):209-16.
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Lederman S, Yellin MJ, Cleary AM, Fortune SM, Chess L. The understanding of contact-dependent T-cell helper function in molecular, cellular and physiological detail. Res Immunol. 1994 Mar-Apr; 145(3):215-21; discussion 244-9.
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