Dr. Walter is Director of the Myelodysplastic Syndrome Program, Professor of Medicine/Genetics, and a Member of the Siteman Cancer Center at Washington University in St. Louis. The major focus of the Walter laboratory is the discovery and characterization of gene mutations in patients with myeloid cancers, with the long-term goal of understanding the molecular mechanisms that control abnormal hematopoiesis. His laboratory used whole genome sequencing to define the clonal architecture and pattern of tumor evolution in patients with myelodysplastic syndrome (MDS) who progressed to secondary acute myeloid leukemia. These studies defined how tumor clonal evolution occurs over time, demonstrating the expansion of rare subclones, a paradigm observed broadly in cancer pathogenesis. These sequencing studies also identified recurrent mutations in U2AF1 (a gene that encodes a spliceosome protein that recognizes the splice acceptor site at the 3’ end of an intron during pre-mRNA splicing) in MDS patients. Walter and colleagues showed that expression of mutant U2AF1 in mice alters pre-mRNA splicing in hematopoietic cells similar to that observed in primary MDS cells. Additional studies using this preclinical model showed that mutant cells have an increased sensitivity to a RNA splicing modulator drug compared to non-mutant cells, nominating a novel approach to treat cancers harboring spliceosome gene mutations. He received his MD degree from St. Louis University, completed a residency and was a chief resident in Internal Medicine at the Johns Hopkins Hospital, and completed a fellowship in Hematology and Oncology at Washington University in St. Louis.
Matthew John Walter, MD