IRCMS International Research Center for Medical Sciences

Research

Goro Sashida

Goro Sashida
Goro Sashida
M.D., Ph.D.
Professor
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Research Field

Hematology, Oncology

Research Interests

To understand how hematopoietic stem cells develop myeloid malignancies:

Myelodysplastic syndrome (MDS) is a group of clonal disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, dysplastic cells in one or more hematopoietic lineages and a predisposition to acute myeloid leukemia (AML). Given that MDS is phenotypically and genetically heterogeneous, the precise molecular mechanisms of the development of MDS remain elusive. Recent high-throughput genome sequencing studies have identified various mutations of epigenetic modifiers in patients with MDS. As epigenetic regulators are critical for normal hematopoiesis, TET2, a member of TET family catalyzing hydroxylation of 5-methylcytosine, is highly expressed in hematopoietic stem cells (HSCs) and Tet2 loss promotes expansion of murine HSCs. Aging is characterized by clonal myeloid-biased hematopoiesis and increases the risk of myeloid malignancies including MDS. Recently, TET2 mutations were identified in normal elderly adults with clonal hematopoiesis, and appears to promote the dysregulation of DNA methylation. Thus, the accumulation of epigenetic alteration can provide pre-MDS/pre-AML reservoir in HSCs and appears to promote the initiation of myeloid malignancies.
Our laboratory are working to determine how genetic and epigenetic alterations collaborate to promote the development of myeloid malignancies by utilizing comprehensive approaches.

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