Hematopoiesis, Stem cell, Transformation, Transcription factor, Epigenetics
To understand how hematopoietic stem cells develop myeloid malignancies: Myelodysplastic syndrome (MDS) is a group of clonal disorders of hematopoietic stem cells characterized by ineffective hematopoiesis, peripheral blood cytopenias, dysplastic blood cells and a predisposition to acute myeloid leukemia (AML). Given that MDS cells are phenotypically and genetically heterogeneous, the molecular mechanism of the development of MDS is incompletely understood. Recent genome sequencing studies have identified various somatic mutations of epigenetic modifiers in patients with myeloid malignancies. Interestingly, the mutations in epigenetic modifiers, which were often seen in MDS cells, were also identified in blood cells of healthy aged adults. Indeed, aging is known to increase the risk of myeloid malignancies including MDS, conceivably due to environmental stress-induced genetic and/or epigenetic alterations. Therefore, the accumulation of epigenetic alterations appears to provide pre-MDS stem cells and facilitate the initiation and propagation of MDS. Our laboratory is working to determine how genetic and epigenetic alterations collaborate to promote the development of myeloid malignancies by utilizing comprehensive approaches (e.g. genetically modified mice, CRISPR/Cas9 genome editing, and sequencing analysis such as CUT & Tag-seq, ATAC-seq, and Bisulfate-seq). We are also working on HMGA/HMGN chromatin modifers in fluke-induced bile duct cancer in collaboration with Dr. Sawanyawisuth in Khon Kaen Univeristy in Thailand and visiting students (please refer to Sawanyawisuth K, et al. Cancers 2021; Sorin S, et al. FASEB J 2022). Several areas of current investigation on malignant hematopoiesis in the lab include:
Goro Sashida recieved his MD from Tokyo Medical University in 1996. He then undertook his PhD in medicine under the supervision of Dr. Kazuma Ohyashiki at the Department of Hematology, Tokyo Medical University in 2002. In 2005, he joined Dr. Stephan Nimer's laboratory at Memorial Sloan-Kettering Cancer Center (New York, USA; Dr. Nimer moved to Miami). In 2009, he moved to Dr. Gang Huang's laboratory at Cincinnati Children's Hospital Medical Center (Ohio, USA; Dr. Huang moved to San Antonio), where he became interested in the study of epigenetic alteration in leukemia. In 2010, he went back to Japan and joined Dr. Atsushi Iwama's laboratory at Chiba University (Chiba, Japan; Dr. Iwama moved to Tokyo). In December 2014, he established his own research group "Laboratory of Transcriptional Regulation of Leukemogenesis" at International Research Center of Medical Sciences, Kumamoto University, and in 2016 he was promoted to Professor. He lives in Kumamoto with his wife, two sons and one daughter.