Our laboratory works in the fields of hematopoiesis, molecular biology, and molecular oncology including mouse modeling of hematopoiesis, myelopoiesis, marrow failure and leukemia. Our 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 the identification of GFI1 mutations in patients with severe congenital neutropenia (SCN) and non-immune chronic idiopathic neutropenia of adults (NI-CINA). The Grimes laboratory has established multiple mouse models of human disease, including acute myeloid leukemia, and more recently SCN. Our work exploits these models to determine fundamental principles of development, delineate disease mechanisms, and drive toward both small-molecule and RNA therapeutics. In Nature, we utilized scRNA-Seq profiling to dissect homeostatic myeloid development and provide deep molecular insight into the process of differentiation. We are actively harnessing both established and cutting-edge single cell technologies to dissect the transcriptional and epigenetic programming of normal and malignant hematopoiesis. In collaboration with Nathan Salomonis we develop biologically-centric informatics algorithms to process single cell data, web portals to disseminate the work flows, and web browsers to make the data easily accessible to biologists.
Research Grants and Contracts
- Mechanisms of Granulocyte Homeostasis. Grimes. Jul 2015-Apr 2024. R01HL122661.
- Normal and Pathological Hematopoietic Stem Cells in Obesity. Reynaud. Apr 2018-Mar 2022. R01 HL141418-02.
- Defining human hematopoietic cells via transcriptomes and methods to isolate them. Grimes. Jan 2020-Dec 2021. R21 HL150678-01.
- Regulation of Functionally Discrete Hematopietic Stem Cells. Grimes. Jan 2020-Mar 2024. R01 DK121062.