H. L. Grimes PhD

H. L. Grimes 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
  • Molecular Carcinogenesis and Chemoprevention

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 HLTherapeutic antagonists of microRNAs deplete leukemia-initiating cell activity.J Clin Invest 124 222-36 1/2/2014
  • 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(9) 3876-88 9/3/2013
  • Aronow BJ, Saba I, Zeng H, Kosan C, Messer MS, Olsson HA, Fraszczak J, Hildeman DA, , Möröy T, Grimes HLGrowth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors.PLoS Genet 9(9) e1003713 9/1/2013
  • 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 in press 7/15/2013
  • Barger JF, Gallo CA, Tandon P, Liu H, Sullivan A, Grimes HL, Plas DRS6K1 determines the metabolic requirements for BCR-ABL survival.Oncogene 32(4) 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
  • 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(25) 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(19) 4006-17 11/8/2012
  • Zhang Y, Yan X, Sashida G, Zhao X, Rao Y, Goyama S, Whitman SP, Zorko N, Bernot K, Conway RM, Witte D, Wang QF, Tenen DG, Xiao Z, Marcucci G, Mulloy JC, Grimes HL, Caligiuri MA, Huang GStress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells.Blood 120(5) 1118-29 8/2/2012

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