Melvin J. and Geraldine L. Glimcher Associate Professor of Immunology and Infectious Diseases
Harvard Affiliations: Instructor in Medicine, Harvard Medical School and Brigham and Women’s Hospital
Fortune Lab Phone: 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.
Current Research Projects
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.
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.
Honors and Awards
Doris Duke Medical Foundation Early Career 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., 1990, Yale University
M.D., 1996, Columbia University, College of Physicians and Surgeons
1. 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. PLoSPathogens. 2010 Jun 24;6(6):e1000957. PMCID: PMC2891827
2. Ford CB, Lin PL, Chase MR, Shah RR, Iartchouk O, Galagan JE, Ioerger TR, Mohaideen N, Sacchettini J, Lipsitch M, Flynn JL and 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. Epub 2011 Apr 24. PMID: 21516081 [PubMed - in process].