A photo of Lee Grimes.

Director, Cancer Pathology Program, Division of Experimental Hematology & Division of Pathology

Co-Leader, Program in Hematologic Malignancies of Cincinnati Children's Hospital Medical Center, Cancer and Blood Diseases Institute

Professor, UC Department of Pediatrics

513-636-6089

513-636-5355

Biography & Affiliation

Biography

Dr. Grimes has a broad background in hematopoiesis, molecular biology, and molecular oncology including 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 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). His work utilizes Gfi1 as a molecular probe to understand both normal myeloid development and innate immune action, as well as marrow failure and transformation.

Research Interests

Acute myelogenous leukemia; T-cell acute lymphoblastic leukemia; severe congenital neutropenia; hematopoiesis; myelopoiesis; lineage decision; transcription factor

Academic Affiliation

Professor, UC Department of Pediatrics

Departments

Experimental Hematology and Cancer Biology, Cancer and Blood Diseases, Immunobiology

Education

PhD: Immunology and Molecular Pathology, University of Florida, Gainesville, FL.

Postdoctoral Fellow: Fox Chase Cancer Center.

Publications

Olsson A, Venkatasubramanian M, Chaudhri VK, Aronow BJ, Salomonis N, Singh H, Grimes HL. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature. 2016 Sep 29;537(7622):698-702.

Meyer SE, Qin T, Muench DE, Masuda K, Venkatasubramanian M, Orr E, Suarez L, Gore SD, Delwel R, Paietta E, Tallman MS, Fernandez H, Melnick A, Le Beau MM, Kogan S, Salomonis N, Figueroa ME, Grimes HL. DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia. Cancer Discov. 2016 May;6(5):501-15.

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 HL. Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity. J Clin Invest. 2014 Jan;124(1):222-36.

Phelan JD, Saba I, Zeng H, Kosan C, Messer MS, Olsson HA, Fraszczak J, Hildeman DA, Aronow BJ, Möröy T, Grimes HL. Growth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors. PLoS Genet. 2013;9(9):e1003713.

Khandanpour C, Phelan JD, Vassen L, Schütte J, Chen R, Horman SR, Gaudreau MC, Krongold J, Zhu J, Paul WE, Dührsen U, Göttgens B, Grimes HL, Möröy T. Growth factor independence 1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia. Cancer Cell. 2013 Feb 11;23(2):200-14.

Horman SR, Velu CS, Chaubey A, Bourdeau T, Zhu J, Paul WE, Gebelein B, Grimes HL. Gfi1 integrates progenitor versus granulocytic transcriptional programming. Blood. 2009 May 28;113(22):5466-75.

Zarebski A, Velu CS, Baktula AM, Bourdeau T, Horman SR, Basu S, Bertolone SJ, Horwitz M, Hildeman DA, Trent JO, Grimes HL. Mutations in growth factor independent-1 associated with human neutropenia block murine granulopoiesis through colony stimulating factor-1. Immunity. 2008 Mar;28(3):370-80.

Kazanjian A, Wallis D, Au N, Nigam R, Venken KJ, Cagle PT, Dickey BF, Bellen HJ, Gilks CB, Grimes HL. Growth factor independence-1 is expressed in primary human neuroendocrine lung carcinomas and mediates the differentiation of murine pulmonary neuroendocrine cells. Cancer Res. 2004 Oct 1;64(19):6874-82.

Person RE, Li FQ, Duan Z, Benson KF, Wechsler J, Papadaki HA, Eliopoulos G, Kaufman C, Bertolone SJ, Nakamoto B, Papayannopoulou T, Grimes HL, Horwitz M. Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2. Nat Genet. 2003 Jul;34(3):308-12.

Grimes HL, Chan TO, Zweidler-McKay PA, Tong B, Tsichlis PN. The Gfi-1 proto-oncoprotein contains a novel transcriptional repressor domain, SNAG, and inhibits G1 arrest induced by interleukin-2 withdrawal. Mol Cell Biol. 1996 Nov;16(11):6263-72.