Harvard Affiliations: Instructor in Medicine, Harvard Medical School and Brigham and Women's Hospital
Fortune Lab: (617) 432-2683
Our laboratory focuses on how M. tuberculosis uses specialized secretion systems and surface structures to mediate interactions with the infected host. We approach these questions using high throughput proteomics and genetic approaches.
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ESX1 Secretion System: While the genes required for the virulence of M. tuberculosis have
been identified, we understand little about the molecular mechanisms of
the bacterium's interactions with the host. One genetic locus, termed
ESX1, is required for the bacterium to cause disease. ESX1 appears to
encode a novel protein secretion system that secretes a number of
proteins of unknown function. We seek to understand how ESX1 and the
ESX1 substrates that we have identified are required for the bacterium
to persist and cause disease in the infected host. |
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Genetic and Epigenetic Variation in M. tuberculosis: We seek to determine whether M. tuberculosis varies, genetically and/or epigenetically, during the course of single infections and whether this variation is subject to selection by the host immune response. With new genomic technologies-low cost genome sequencing and expression profiling we are systematically assessing genetic and epigenetic variation in bacteria selected in experimental models of disease.
Hypermutability and the Acquisition of Multidrug Resistance: We are assessing whether differences in the mutability between different strains of tuberculosis account for the emergence of extended drug resistance in some clinical strains. We are developing assays for testing mutability in drug sensitive and drug resistant strains of M. tuberculosis and directly measuring the mutability of clinical strains that have acquired or given rise to multidrug resistant tuberculosis.
NIH New Innovator Award
Howard Hughes Medical Institute Physician Scientist Early Career Development Award
The Maxwell Finland Award
for Excellence in Research, Massachusetts
Infectious Disease Society
Harvard Medical School
Teaching Award for Residents in Internal Medicine
Alpha Omega Alpha
B.S. Yale University, 1990
M.D. Columbia University, College of Physicians and Surgeons, 1996
1. Fortune SM, Jaeger A, Sarracino DA, Chase MR, Sassetti CM, Sherman DR, Bloom BR and Rubin EJ. Mutually-dependent secretion of proteins required for mycobacterial virulence. PNAS, 2005 Jul 26;102(30):10676-81
2. Fortune SM, Solache A, Jaeger A, Hill PJ, Belisle JT, Bloom BR, Rubin EJ, and 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.
