H. Grimes L. PhD

H. Grimes L. PhD
Assoc ProfessorCollege of Medicine--UClee.grimes@cchmc.org
Division of Immunobiology - MLC 7038 3333 Burnet Ave, Room 5564 Cincinnati OH 45229
Phone:(513) 636-6089Fax: (513) 636-5355
  • Leukemia Research

General Research Interest

Transcriptional and epigenetic regulation of hematopoiesis and leukemogenesis

Research Description

Dr. Grimes was part of a team that first discovered the Growth factor independent-1 transcription factor which controls blood development and cancer, and he has shown that this factor is mutant in children with severe congenital neutropenia (SCN). Children with SCN lack neutrophils, blood cells which fight infection, and are thus prone to bacterial and fungal infections. Moreover, SCN patients are at dramatically increased risk for acute myeloid leukemia. The Grimes lab studies transcriptional and epigenetic signaling circuits in normal and cancerous blood development using human, mouse and fruitfly genetic models to gain insight into ancient pathways that underlie cancer. Using these tools they have 1) generated the first mouse model of SCN, 2) discovered critical genes that are disregulated in SCN, and 3) uncovered a key epigenetic component of myeloid development and transformation to acute myeloid leukemia.

Transinstitutional Work

H. Leighton Grimes Ph.D. is a tenured Associate Professor at the Cincinnati Children’s Hospital Medical Center. He is the recipient of a Scholar Award from the Leukemia and Lymphoma Society of America for his work on transcriptional repression mechanisms in myeloid leukemia. Moreover, he is the Director of the Joint Cancer Pathology Program of the Division of Experimental Hematology and the Division of Pathology at the Cincinnati Children’s Hospital. His work is funded by the National Cancer Institute, the National Heart Lung and Blood Institute and several independent international organizations.

Current Publications

  • Grimes H Leighton, Olsson A, Aronow Bruce, Chaudhri V, Dexheimer P, Singh HSingle cell transcriptome-based dissection of lineage fate decisions in myelopoiesis.Exp Hematol 42 S21 8/1/2014
  • Karp CL, Boespflug ND, Kumar S, McAlees JW, Phelan JD, Grimes HL, Hoebe K, Hai T, Filippi MDATF3 is a novel regulator of mouse neutrophil migration.Blood 123 2084-93 3/27/2014
  • Tidwell T, Wechsler J, Nayak RC, Trump L, Salipante SJ, Cheng JC, Donadieu J, Glaubach T, Corey SJ, Grimes HL, Lutzko C, Cancelas JA, Horwitz MSNeutropenia-associated ELANE mutations disrupting translation initiation produce novel neutrophil elastase isoforms.Blood 123 562-9 1/23/2014
  • Velu CS, Chaubey A, Phelan JD, Horman SR, Wunderlich M, Guzman ML, Jegga AG, Zeleznik-Le NJ, Chen J, Mulloy JC, Cancelas JA, Jordan CT, Aronow BJ, Marcucci G, Bhat B, Gebelein B, Grimes HLTherapeutic antagonists of microRNAs deplete leukemia-initiating cell activity.J Clin Invest 124 222-36 1/2/2014
  • Guo F, Li J, Zhang S, Du W, Amarachintha S, Sipple J, Phelan J, Grimes HL, Zheng Y, Pang QmTOR kinase inhibitor sensitizes T-cell lymphoblastic leukemia for chemotherapy-induced DNA damage via suppressing FANCD2 expression.Leukemia 28 203-6 1/1/2014
  • Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, Nakagawa M, Olsson A, Wunderlich M, Link KA, Mizukawa B, Grimes HL, Kurokawa M, Liu PP, Huang G, Mulloy JCTranscription factor RUNX1 promotes survival of acute myeloid leukemia cells.J Clin Invest 123 3876-88 9/3/2013
  • Barger JF, Gallo CA, Tandon P, Liu H, Sullivan A, Grimes HL, Plas DRS6K1 determines the metabolic requirements for BCR-ABL survival.Oncogene 32 453-61 1/24/2013
  • Taniguchi Ishikawa E, Chang KH, Nayak R, Olsson HA, Ficker AM, Dunn SK, Madhu MN, Sengupta A, Whitsett JA, Grimes HL, Cancelas JAKlf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated β1/β2-integrin trafficking.Nat Commun 4 1660 1/1/2013
  • Phelan JD, Saba I, Zeng H, Kosan C, Messer MS, Olsson HA, Fraszczak J, Hildeman DA, Aronow BJ, Möröy T, Grimes HLGrowth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors.PLoS Genet 9 e1003713 1/1/2013
  • Unnisa Z, Clark JP, Roychoudhury J, Thomas E, Tessarollo L, Copeland NG, Jenkins NA, Grimes HL, Kumar ARMeis1 preserves hematopoietic stem cells in mice by limiting oxidative stress.Blood 120 4973-81 12/13/2012
  • Khandanpour C, Krongold J, Schütte J, Bouwman F, Vassen L, Gaudreau MC, Chen R, Calero-Nieto FJ, Diamanti E, Hannah R, Meyer SE, Grimes HL, van der Reijden BA, Jansen JH, Patel CV, Peeters JK, Löwenberg B, Dührsen U, Göttgens B, Möröy TThe human GFI136N variant induces epigenetic changes at the Hoxa9 locus and accelerates K-RAS driven myeloproliferative disorder in mice.Blood 120 4006-17 11/8/2012

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) 300 W. 10th Ave. Columbus, OH 43210 Phone: 1-800-293-5066 | Email: jamesline@osumc.edu