Matthew Meyerson began his research group at Dana-Farber Cancer Institute in 1998 with the goal of using genomic approaches to understand the causes of human cancer, with a focus on lung cancer, and to apply this new understanding to the development of effective treatments that kill cancer cells while sparing healthy cells.
Our research uses genomic and genetic approaches to understand the causes of human cancer, with a particular focus on lung cancer. Through these studies, we are inspired to explore the biology of genes that are mutated in cancer and to develop therapeutic approaches that target the unique biology of cancer cells.
For the past 25 years, we have developed, optimized, and deployed state-of-the-art technologies to describe the somatic genomes in cancer, from array technologies to next-generation sequencing and now to long-read sequencing approaches. Using these approaches, we have discovered many of the key genes subject to somatic mutation and focal copy number change in lung cancers and beyond.
Our current focus is to apply long-read sequencing technologies to discover structural alterations in repetitive regions of cancer genomes. We are also interested in defining the germline risk factors for somatic mutation, focusing on germline variation in somatic EGFR mutation frequency in lung cancer.
As we discover genome alterations that occur during the development of human lung cancer, we ask whether and how these genome alterations contribute to cancer development. Our functional studies range from the development of methods to study chromosomal aneuploidy in model systems to the analysis of the function of specific genes in lung cancer models, both genes acting in known cancer pathways (e.g. EGFR) and in yet-to-be ascertained impacts on cancer pathogenesis (e.g. U2AF1, CMTR2).
We have been applying our knowledge of cancer genomes to inspire our efforts in cancer drug discovery. Our focus has been on screens for TP53 mutant synthetic lethality, leading serendipitously to our finding of PDE3A-SLFN12 phosphodiesterase-ribonuclease complex inducers, on amplified genes including PPARG, and on EGFR and ERBB2 mutants with emphasis on the exon 20 insertion mutants. This work has now led to two compounds in clinical trials, BAY2666605 for melanoma and BAY2927088 for EGFR/ERBB2 mutant lung cancer.
Our discovery of the association of Fusobacterium species with colorectal carcinoma, followed by the finding that Fusobacterium-positive colorectal cancers can be antibiotic-sensitive, have opened up the field of studying the microbiome in human cancer. As co-leader of the OPTIMISTICC program of the Cancer Grand Challenges, our group is focused on understanding the cellular consequences of Fusobacterium infection.