Timothy J. Ley
Washington University in St. Louis
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Primary Section: 41, Medical Genetics, Hematology, and Oncology Membership Type:
Member
(elected 2019)
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Biosketch
Timothy J. Ley, M.D. is a physician-scientist recognized for his work in cancer genomics. He is known for his studies of the genetic and epigenetic factors relevant for the pathogenesis of Acute Myeloid Leukemia, leading to new ways to classify and more precisely treat patients with this disease. Ley was born and raised in Lakota, Iowa, received his B.A. from Drake University in Biology, his M.D. degree from Washington University Medical School, and performed his internal medicine residency at Massachusetts General Hospital. He completed fellowships in Hematology and Oncology at the NIH and at Washington University, and joined the faculty at Washington University in St. Louis in 1986. Ley is a past president of the American Society for Clinical Investigation, past treasurer of the American Association of Physicians, a fellow of AAAS and the American Academy of Arts and Sciences, and a member of the National Academy of Medicine and National Academy of Sciences. He was appointed by President Obama to the National Cancer Advisory Board in 2015.
Research Interests
Ley studies the molecular pathogenesis of Acute Myeloid Leukemia (AML). He and his colleagues sequenced the first human cancer genomes from patients with AML, and led The Cancer Genome Atlas study of AML patients. These studies established the mutational landscape of AML, and many of the epigenetic events that are important for its pathogenesis. DNMT3A, which encodes one of the two de novo DNA methyltransferases, is the most common AML-initiating mutation, occurring in a third of patients with normal karyotype disease. DNMT3A mutations are the most common cause of clonal expansion of blood cell progenitors in the elderly (Age Related Clonal Hematopoiesis/ARCH), a condition that greatly increases the risk of developing AML. Loss of DNMT3A function leads to the development of thousands of hypomethylated regions in the genomes of hematopoietic cells, but only subtle effects on gene expression. The lab is using mouse models and state-of-the-art epigenetic techniques to fully define the consequences of DNMT3A mutations in hematopoietic cells, establishing the mechanisms by which missense mutations alter DNMT3A activities, and exploring ways to restore normal DNMT3A function in hematopoietic cells with these mutations.
