Oncology Division
Alphabetical list (active faculty):   
Matthew J. Walter

Matthew J. Walter, MD

Edward P. Evans Endowed Professor of Myelodysplastic Syndromes


Department of Medicine

Oncology Division

Bone Marrow Transplantation & Leukemia

Stem Cell Biology

Department of Genetics

Clinical Interests

  • Myelodysplastic syndromes
  • Acute myeloid leukemia

Research Interests

  • Functional genomics
  • Tumor biology
  • Hematopoiesis


  • 314-362-9409 (office)
  • 314-362-9333 (fax)
  • Oncology Division
    Mail Stop 8007-0057-06
    Washington University
    660 South Euclid Avenue
    St. Louis, MO 63110
  • Southwest Tower Room 622 (office)
  • Southwest Tower Room 613L (lab)


The main interest of our laboratory is the discovery and characterization of gene mutations in patients with myelodysplastic syndrome (MDS) with the long-term goal of understanding the molecular mechanisms that control abnormal hematopoiesis. MDS results from the expansion of one or more dominant hematopoietic clones that contain initiating somatic mutations, while transformation from MDS to acute myeloid leukemia (AML) occurs as these clones accumulate additional progression factors (including point mutations in genes and cytogenetic abnormalities).

Research is ongoing in the following areas:

MDS genomics and tumor clonal heterogeneity

Gene mutations are identified in the genomes of hematopoietic cells from patients with MDS and AML using next generation sequencing technology, including whole genome sequencing. Somatic mutations are used to decipher the clonal architecture of MDS and AML samples (ie, founding clones and subclones). The functional significance of recurrently mutated genes is then studied using primary human hematopoietic cells and mouse models to understand the mechanisms of disease pathogenesis.

The role of splicing gene mutations in MDS pathogenesis

Ongoing projects are focused on understanding the mechanism of MDS initiation and progression induced by mutations in genes that participate in pre-mRNA splicing identified by our group and others. Spliceosome gene mutations occur in 50% of MDS patients. Functional splicing assays, next-generation sequencing technology, and hematopoietic assays will be used to study primary human cells and mouse models harboring mutations. Preclinical cell and mouse models are being used to test novel approaches to selectively kill spliceosome mutant cells with the goal of introducing new therapies into clinical trials for MDS patients.

Monitoring tumor burden using next-generation sequencing

Gene mutations are identified in patient samples using whole genome and exome sequencing. The abundance of tumor-specific mutations are tracked in serial samples using error-corrected sequencing during treatment to objectively monitor tumor burden and treatment response. The prognostic utility of these approaches are being tested in clinical trials to improve patient outcomes.

All these studies involve state of the art technologies and incorporate functional genomics, bioinformatics, next-generation sequencing, stem cell and tumor biology, and mouse models of disease to study hematopoiesis.



Missense mutations were detected in codons 34 and 157 of U2AF1 in 11% of patients with myelodysplastic syndromes (MDS)

Shirai et al. show that the U2AF1 mutation most commonly found in MDS alters pre-mRNA splicing in RNA processing genes, ribosomal genes, and recurrently mutated MDS and acute myeloid leukemia-associated genes in hematopoietic progenitor cells and affect hematopoiesis.

From: Mutant U2AF1 expression alters hematopoiesis and pre-mRNA splicing in vivo.
Cancer Cell 2015 May 11;27(5):631-43