BBS Faculty Member - Matthew Meyerson

Matthew Meyerson

Department of Pathology

Dana Farber Cancer Institute
Dana Bldg., Rm. 1540
450 Brookline Ave.
Boston, MA 02215

Assistant: Julie Hammond-Coiro
Juliem_hammond-Coiro@dfci.harvard.edu

Tel: 617-632-4768
Fax: 617-582-7880
Email: matthew_meyerson@dfci.harvard.edu
Lab Members: 14 postdoctoral fellows, 2 graduate students



We strive to discover genomic events that cause human cancers and infectious causes for diseases of unknown origin. We then seek to apply these discoveries to improving diagnosis and treatment for these diseases. One particular focus is lung cancer pathogenesis and targeted therapy.

Somatic genetic alterations in cancer: We use genome-scale approaches to discover chromosomal alterations and cancer-causing mutations. Our group is active in The Cancer Genome Atlas (TCGA) project to perform multi-modality analyses of human cancers, where I lead the copy number and lung cancer efforts. By analysis of somatic copy number alterations, we have defined both lineage-specific and cancer-universal regions of amplification and deletion (Beroukhim et al., 2010; Zack et al., 2013). We identified the most common DNA amplification in lung adenocarcinoma as targeting NKX2-1, a lung lineage-determining transcription factor (Weir et al., 2007) and in squamous cell lung carcinoma as targeting SOX2, also a lineage-specific transcription factor (Bass et al., 2009).

By cancer sequencing, we detected activating mutations in kinase genes including the epidermal growth factor receptor tyrosine kinase gene,
EGFR, in lung adenocarcinomas (Paez et al., 2004) and in glioblastomas (Lee et al., 2006), FGFR2 in multiple cancers (Dutt et al., 2008), ALK in neuroblastoma (George et al., 2008) and DDR2 in squamous cell lung carcinoma (Hammerman et al., 2011).

We pioneered the use of next-generation sequencing in cancer genome analysis (Thomas et al., 2006) and have developed methods for analysis of cancer heterogeneity (Carter et al., 2012) and single cell sequencing (Francis et al., 2014). Recent sequencing discoveries have included recurrent translocations of
TCF7L2 in colon cancer (Bass et al., 2011), loss-of-function mutations in HLA genes in lung and cervical cancers (TCGA, 2012; Ojesina et al 2014), suggesting a mechanism for immune evasion in these tumor types, mutations of splicing factor genes U2AF1 and RBM10 in lung adenocarcinoma (Imielinski et al., 2012), and mutations of the cell cycle regulator CDKN1B in small intestinal neuroendocrine tumors, or carcinoids (Francis et al., 2013).

Functional analysis of lung cancer genes: We work to understand transformation by the major oncogenes that cause lung cancer, focusing on EGFR, the Ras pathway, and NKX2-1, and to apply this understanding to lung cancer therapy. We showed that distinct EGFR mutants are differentially sensitive to distinct inhibitors (Greulich et al., 2005) and have uncovered a role for EGFR dimerization in modulating susceptibility to inhibitors in lung and colorectal cancers (Cho et al., 2013; Cho et al., 2014), establishing the concept of mutant-selective therapy. We are now studying a large number of novel oncogenic mutants identified in genome sequencing screens (Imielinski et al., 2012) while actively pursuing targeted therapies in the EGFR pathway.

Discovery of pathogenic microbes: We developed a novel approach to discover microbial sequences in cryptic infectious diseases, by sequencing DNA from diseased tissues and removing sequences that match the human genome computationally, leaving microbial sequences (Weber et al., 2002; Kostic et al., 2011). We have applied these methods to uncover a pathogenic basis for the transplant-associated cord colitis syndrome (Bhatt et al, 2013). Furthermore, we have identified an enrichment of Fusobacterium nucleatum in colorectal carcinoma (Kostic et al., 2012) and have obtained evidence supporting a role for Fusobacterium in mediating intestinal carcinogenesis (Kostic et al., 2013).



Last Update: 6/20/2014



Publications

For a complete listing of publications click here.

 


 

Kostic AD, Chun E, Robertson L, … Fuchs CS, Meyerson M, Garrett WS (2013). Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14(2):207-15.

Bhatt AS, Freeman SS, Herrera AF, … Hornick JL, Marty FM, Meyerson M (2013). Sequence-based discovery of Bradyrhizobium enterica in cord colitis syndrome.
N Engl J Med 369(6):517-28.

Cancer Genome Atlas Research Network. Meyerson M, corresponding author (2012). Comprehensive genomic characterization of squamous cell lung cancers.
Nature 489(7417):519-25.

Imielinski M, Berger AH, Hammerman PS, … Garraway LA, Getz G, Meyerson M (2012). Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing.
Cell 150(6):1107-20.

Beroukhim R, Mermel CH, Porter D, … Getz G, Sellers WR, Meyerson M (2010). The landscape of somatic copy-number alteration across human cancers.
Nature 463:899-905.



© 2014 by the President and Fellows of Harvard College