H. Leighton Lee Grimes

About H. Leighton Lee Grimes

I have a broad background in hematopoiesis, molecular biology, and molecular oncology including mouse modeling of hematopoiesis, myelopoiesis, marrow failure syndromes and leukemia. I participated in the identification of the Growth factor independent-1 (Gfi1) transcription factor, its DNA binding specificity, named the “SNAG” transcription repressor domain, and genetically linked this domain to Gfi1-directed biology. After establishing the Grimes lab, we collaborated with Marshall Horwitz (U. Wash) to identify humans with mutations in GFI1, who display severe congenital neutropenia (SCN) and non-immune chronic idiopathic neutropenia of adults (NI-CINA). In Nature 2016, the Grimes lab was one of the first labs to utilize deep scRNA Seq profiling to dissect homeostatic myeloid development and provide deep molecular insight into the process of differentiation. In Nature 2020, they generated the first mouse models of human SCN using patient-derived mutations in the GFI1 transcription factor. This work explained why SCN patients on recombinant GCSF therapy still need antibiotics, and underscored the importance of evaluating the effects of mutations and therapy within each relevant cell state. In Nature Immunology 2024 they produced a multiomics atlas of human marrow stem and progenitors that is durable across multiple human biological variables, and an accompanying online tool to mine the data. These rigorously defined clusters can organize human genomic data from multiple sources, including AML. Most recently, they showed that ancestry impacts the integration of NPM1c oncogenesis, and that incorporation of ancestry-specific risk markers changes risk group assignment and improved their outcome prediction. Work is underway to functionalize novel recurrent AML mutations associated with ancestry, and understand oncogene collaboration, leukemia stem cells and therapeutic liabilities that underlie disparity in clinical outcomes. The Grimes lab is actively harnessing both established and cutting-edge single cell and induced pluripotent stem cell technologies (marrow organoids and AML-to-iPSC-to-AML) to dissect the transcriptional and epigenetic programming of normal and malignant hematopoiesis. In collaboration with Nathan Salomonis (CCHMC) they 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.

Experience

1. Professor, Division of Immunobiology

   Cincinnati Children's

   Jan 2014 — Present · Cincinnati, OH, US

Education

• Loyola University New Orleans

  Bachelor of Science (B.S.), Biology, General

  1980 — 1985

• University of Florida

  Doctor of Philosophy (Ph.D.), Molecular Pathology and Immunology

  1985 — 1992

Skills

• Science
• Research
• In Vivo
• Leukemia
• Cell Biology
• Genetics
• Laboratory
• Cancer
• Cell Culture
• Protein Chemistry
• Hematopoiesis
• Rna Therapeutics
• Molecular Biology
• Cancer Research
• Therapists
• Clinical Research
• Molecular Oncology
• Pediatric Hematology/Oncology
• Cell