Tel: 617 432 6965
My laboratory focuses on the molecular basis of population heterogeneity in Mycobacterium tuberculosis (Mtb) and the extent to which differences between mycobacterial cells contribute to differences in disease and treatment outcomes. I am committed to providing training in bacterial genetic approaches with high throughput methodologies. Trainees are exposed to TnSeq, high density whole genome sequencing, RNAseq and quantitative live cell imaging to define the molecular mechanisms by which Mtb generates diversity and how this diversity enables the bacterium to survive subsequent selective forces including antibiotics and immune selection. We further seek to understand the impact of host immune responses on the interaction of Mtb with the infected host, again working at both single cell and genomic levels. My work engages a broad network of collaborators including experts in technologies to assess single cell behavior at MIT and MGH, experts in sequencing methodologies at the Broad Institute and experts in human immunology at the Ragon Institute, where I am the Director of the TB Program.
These studies illustrate our efforts to combine novel genomic and classic bacterial genetic approaches to rapidly address clinically relevant questions in tuberculosis.
Rock JM, Hopkins FF, Chavez A, Diallo M, Chase MR, Gerrick ER, Pritchard JR, Church GM, Rubin EJ, Sassetti CM, Schnappinger D, Fortune SM. Programmable transcriptional repression in mycobacteria using an orthogonal CRISPR interference platform. Nat Microbiol. 2017 Feb 6;2:16274. PubMed PMID: 28165460; PubMed Central PMCID: PMC5302332
Carey AF, Rock JM, Krieger IV, Chase MR, Fernandez-Suarez M, Gagneux S, Sacchettini JC, Ioerger TR, Fortune SM. TnSeq of Mycobacterium tuberculosis clinical isolates reveals strain-specific antibiotic liabilities. PLoS Pathog. 2018 Mar 5;14(3):e1006939. doi: 10.1371/journal.ppat.1006939. PMID: 2950561; PMCID: PMC5854444.
Hicks ND, Yang J, Zhang X, Zhao B, Grad YH, Liu L, Ou X, Chang Z, Xia H, Zhou Y, Wang S, Dong J, Sun L, Zhu Y, Zhao Y, Jin Q, Fortune SM. Clinically prevalent mutations in Mycobacterium tuberculosis alter propionate metabolism and mediate multidrug tolerance. Nat Microbiol. 2018 Sep;3(9):1032-1042. doi: 10.1038/s41564-018-0218-3. Epub 2018 Aug 6. PMID: 30082724