Matthew Langer Meyerson

Matthew Langer Meyerson

Professor of Genetics and Medicine
Matthew Langer Meyerson

We strive to discover genomic and infectious causes for human cancers. We then seek to apply these discoveries to understand mechanisms of cancer pathogenesis, and to improve cancer diagnosis and treatment. A particular focus is lung cancer pathogenesis and targeted therapy, including research on new therapeutic compounds and modalities.

Somatic genetic alterations in cancer: We use genome sequencing to discover somatic alterations in cancer genomes. Areas of focus include lung cancer driver mutations; non-coding cancer genome alterations; and the connection between germline risk and somatic mutation in lung cancer.

Comprehensive characterization of lung cancer driver mutations: Genomic analysis of non-small cell lung cancer in our laboratory has led to the discovery of multiple activated oncogenes, including BRAF (Naoki, 2002), EGFR (Paez, 2004), NKX2-1 (Weir, 2007), SOX2 (Bass, 2009), U2AF1 (Imielinski, 2012), and inactivated tumor suppressor genes, including RBM10 (Imielinski, 2012) and CMTR2 (Campbell, 2016). Now we are analyzing the largest case series yet of lung cancer somatic mutation data and hope to find more.

Analysis of non-coding cancer genome alterations using long-read sequencing data. We found that non-coding genome alterations are essential for cancer pathogenesis. We have identified and analyzed enhancer duplications near the MYC (Zhang, 2016) and KLF5 (Zhang, 2017) genes in lung and other cancers. Using linked-read sequencing, we identified similar enhancer duplications near the androgen receptor gene in prostate cancer (Viswanathan, 2018). Our current focus is on long-read sequence analysis of repetitive elements such as telomeres.

Germline risk and somatic mutation in lung cancer. Somatic mutations in EGFR occur in ~10% of cancers from patients of European and African descent and ~50% of cancers from patients of East Asian descent (Paez, 2004; Campbell, 2017). EGFR somatic mutations occur at intermediate frequencies in lung cancers from patients in Latin America, where mutation frequency correlates with Native American ancestry (Carrot-Zhang, 2021). We are exploring this correlation to search for a germline risk factor for somatic EGFR mutations.

Functional analysis of lung cancer genes: We work to understand transformation by the major genes that cause lung cancer, with a focus on EGFR (Sharifnia, 2014), U2AF1, CMTR2, and NKX2-1 (Watanabe, 2013), as well as lung cancer aneuploidy (Taylor, 2018), using biochemical, functional genomic, and animal approaches.

The cancer microbiome: We developed the computational subtraction approach to find microbial sequences in human disease (Weber, 2002). We identified Fusobacterium enrichment in colorectal carcinoma (Kostic, 2011) and showed that Fusobacterium is associated with colon cancer metastasis and response to antibiotics in model systems (Bullman, 2017). We are continuing to study whether Fusobacterium plays a role in cancer pathogenesis, and also to analyze T cell receptor sequences that recognize microbial and cancer antigens (Lee & Meyerson, 2021).

Targeted cancer therapeutics: We seek to apply cancer genome understanding to the development of new therapies. Two molecules based on our research are currently in clinical trial, one based on our finding that EGFR exon 20 insertion mutations are resistant to many therapies (Greulich, 2005) and one based on our discovery of “velcrins”, molecular glues that bring together the PDE3A and SLFN12 proteins (de Waal, 2016).

 

Contact Information

Dana-Farber Cancer Institute
Dana Building, Room D1540
44 Binney Street
Boston, MA 02115

Assistant: Julie Hammond-Coiro
Juliem_hammond-Coiro@dfci.harvard.edu
p: 617-632-4768

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