Organization
Cincinnati Childrens Hospital Medical Center
Profile
-
-
Biography
Dr. Grimes started in the Division of Immunobiology at Cincinnati Children’s Hospital Medical Center as an Associate Professor (with tenure). Later, he became a member of the Division of Experimental Hematology and Cancer Biology. He is currently the Co-Leader of the Hematologic Malignancies Program of the Cancer and Blood Disease Institute, and the Director of the Cancer Pathology Program; a shared program of the Divisions of Pathology and Experimental Hematology. Dr. Grimes has a broad background in hematopoiesis, molecular biology, and molecular oncology including mouse modeling of hematopoiesis, myelopoiesis and leukemia. His work on the Growth factor independent-1 (Gfi1) transcriptional repressor protein has spanned the initial identification of Gfi1 in a mouse model of leukemia and the role of Gfi1 in normal myeloid biology, to work in Nature Medicine with Marshall Horwitz in which he identified GFI1 mutations in patients with severe congenital neutropenia (SCN) and non-immune chronic idiopathic neutropenia of adults (NI-CINA). In Immunity and Blood he identified Csf1, miR-21 and miR-196b as functional targets of Gfi1 that control the SCN-associated Gfi1-mutant block to granulopoiesis. SCN patients are at a tremendous risk for transformation to AML. To potentially explain this risk, he published a series of papers in Molecular Cell and Blood in which he illustrated an ancient Gfi1 versus HoxA9-Pbx1-Meis1 transcriptional circuit present from Drosophila anterior-posterior development to myeloid progenitor maintenance and transformation. This lead to a recent JCI paper showing that these factors antagonize the expression of two microRNA genes, and that RNA therapeutics which specifically block the microRNA can cure the mouse model of 11q23-translocation-oncoprotein induced AML. In Cancer Cell, he again utilized RNA therapeutics to show that Gfi1 is actually required for the continued survival of transformed lymphoid cells, including T cell acute lymphoblastic leukemia (T-ALL) and B-ALL. In the latter two projects, he moved the project to preclinical translation through the use of RNA therapeutics to block leukemia stem cell activity.