Matthew J. Walter, M.D.
- Assistant Professor
- Department of Medicine
- Oncology Division
- Stem Cell Biology Section
- Oncology Division
- Department of Genetics
- Department of Medicine
- Clinical interests
- Myelodysplastic syndromes
- Acute myeloid leukemia
- Research interests
- Functional genomics
- Tumor biology
- Hematopoiesis
Research
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 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).
Current projects include the following:
Discovery of gene mutations that occur in the genomes of hematopoietic cells from patients with myelodysplastic syndromes (MDS)
Our laboratory is using high-throughput genomic resequencing to analyze candidate genes that may be important for the pathogenesis of MDS. Functional studies of mutant genes will be performed to understand how the normal and abnormal gene products affect hematopoiesis.
Characterization of genomic copy number alterations in MDS
Small chromosomal abnormalities, undetectable by standard cytogenetic analysis, may contribute directly to MDS pathogenesis. To address this possibility, we are using an array comparative genomic hybridization (aCGH) platform that contains ~385,000 long oligomer probes spanning the entire genome with 6 kilobase average spacing. This platform can detect cytogenetically "silent" copy number changes in the genomes of hematopoietic cells from MDS patients. We are annotating the genes encompassed by these copy number changes and evaluating their contribution to MDS pathogenesis using both mouse models systems and primary human cells.
Define the molecular mechanisms that control abnormal hematopoiesis in MDS
Several genes located on a chromosomal region that is commonly deleted in MDS have been implicated in hematopoiesis. The laboratory is utilizing RNA interference (RNAi) in primary human and murine hematopoietic cells to study how gene dosage alters hematopoiesis. Knockout mice are being generated for specific MDS candidate genes in order to directly study their contribution to hematopoiesis in mice.
|
Summary of genetic alterations in AML genomes Pie chart demonstrates the relative proportions of AML samples with an abnormal (red, n = 50) and normal (white, n = 36) karyotype, with (+) and without (-) copy number alterations (CNAs) and uniparental disomy (UPD) detected by SNP arrays. The number of patients in each group is listed in parentheses. Of 36 patients with a normal karyotype, 13 (36%) had a CNA or UPD (identified as SNP Array Specific CNA or UPD). Of 50 patients with an abnormal karyotype, 21 (42%) had an SNP array-specific CNA (not seen by cytogenetics) or UPD detected by SNP arrays (identified as SNP Array Specific CNA or UPD). Forty-three of 86 patients (50%) had no CNA or UPD detected by SNP arrays.
From: Walter MJ, Payton JE, Ries RE, et al.
|
Biographical Sketch
Education
| 1990 | B.S., American University, Washington, DC |
| 1995 | M.D., St. Louis University School of Medicine, St. Louis, MO |
Post-graduate Training
| 1992-1993 | Howard Hughes Medical Institute - National Institutes of Health Research Scholar, Bethesda, MD (Steven Jacobson, PhD, Mentor) |
| 1995-1996 | Intern in Medicine, Johns Hopkins Hospital, Baltimore, MD |
| 1996-1998 | Resident in Medicine, Johns Hopkins Hospital, Baltimore, MD |
| 1998-1999 | Hematology-Oncology Fellow, Washington University Medical Center, St. Louis, MO |
| 1999-2000 | Assistant Chief of Service (Chief Medical Resident), Johns Hopkins Hospital, Baltimore, MD |
| 2000-2004 | Hematology-Oncology Fellow, Washington University Medical Center, St. Louis, MO |
| 2001-2004 | Post-Doctoral Fellow, Washington University, St. Louis, MO (Timothy Ley, MD, Mentor) |
Academic Positions
| 2004-2005 | Instructor of Medicine, Washington University School of Medicine, St. Louis, MO |
| 2005-present | Assistant Professor of Medicine, Washington University School of Medicine, St. Louis, MO |
| 2005-present | Assistant Professor of Genetics, Washington University School of Medicine, St. Louis, MO |
Board Certification
| 1998 | American Board of Internal Medicine |
| 2002 | American Board of Internal Medicine, Oncology |
| 2002 | American Board of Internal Medicine, Hematology |
Honors & Awards
| 1991 | Eben J. Carey Memorial Award in Anatomy, St. Louis University School of Medicine |
| 1991-1992 | American Federation for Aging Research Fellow, Research Scholarship in Geriatric Pharmacology, St. Louis University School of Medicine, St. Louis, MO |
| 1991-1992 | Hartford Fellow, John A. Hartford Foundation for Geriatric Research, St. Louis University School of Medicine, St. Louis, MO |
| 1992-1993 | Howard Hughes Medical Institute - National Institutes of Health Research Scholar, Bethesda, MD |
| 1994 | Alpha Omega Alpha Honor Medical Society, St. Louis University School of Medicine |
| 1995 | Medical Degree with Distinction in Research, St. Louis University School of Medicine |
| 2003-2004 | Leukemia Research Foundation Physician-Scientist Postdoctoral Fellowship |
| 2003-present | NHLBI Loan Repayment Program recipient |
| 2005-2007 | American Society of Hematology Scholar Award |
| 2007-2012 | Howard Hughes Medical Institute Physician-Scientist Early Career Award |
Professional Societies
| American Society of Hematology |
- Updated: August 14, 2009
