The Grimes Lab investigates the interface between normal and malignant blood development. The lab uses state of the art biological and molecular tools to delineate transcriptional and microRNA signaling.
I am between my 2nd and 3rd year as a medical student at Northeast Ohio Medical University. I am deeply interested in the field of hematology, so I applied and received the ASH Physician Scientist Development Award to work in the Grimes Lab and shadow Dr. Ashish Kumar in Cincinnati Children’s Hematology Clinic. My basic research project is to develop new mouse models for common mutations of AML. To that end, I am designing, cloning and testing guide RNA using the CRISPR Cas9 system to target known common mutations that lead to malignancy in humans. My primary focus is to test the impact of these mutations on disease severity and response to standard induction chemotherapy.
Research Assistant II
Lab Phone: 513-636-6096
I received a Master’s Degree in Biomedical Engineering from the University of Louisville, working with Donald Miller, the Director of the Brown Cancer Center. My work was focused on nucleic acid therapeutics in cancer. I am now a PhD candidate in the Molecular and Developmental Biology program at Cincinnati Children’s. My graduate work in the Grimes lab focuses on elucidating the transcriptional programs underlying normal and malignant hematopoiesis. The transcription factor GFI1 is required for hematopoietic stem cell fitness and granulopoiesis. I am working on three projects:
“Environmental Carcinogenesis and Mutagenesis” Training Program (T32ES007250-06), 2015-Current
Meyer, S.E., Qin, T., Muench, D.E., Masuda, K., Venkatasubramanian, M., Orr, E., Suarez, L., Gore, S.D., Delwel, R., Paietta, E., Tallman, M.S., Fernandez, H., Melnick, A., Le Beau, M.M., Kogan, S., Salomonis, N., Figueroa, M.E., and Grimes, H.L. DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia. Cancer Discovery. 2016 May;6(5):501-15. PMID: 27016502.
Muench, D.E., Grimes, H.L. Transcriptional Control of Stem and Progenitor Potential. Springer Stem Cell Reports. 2015 Sep:1(3): 139-150. PMID: 26509110.
Cumaraswamy, A. A., Lewis, A.M., Geletu, M., Todic, A., Diaz, D.B., Cheng, X.R., Brown, C.E., Laister, R.C., Muench, D., Kerman, K., Grimes, H.L., Minden, M.D., and Gunning, P.T. Nanomolar-Potency Small Molecule Inhibitor of STAT5 Protein. ACS Medicinal Chemistry Letters. 2014 Sep 19;5(11): 1202-1206. PMID: 25419444.
Miller, D.M., Thomas, S.D., Islam, A., Muench, D., and Sedoris, K.C. c-Myc and cancer metabolism. Clinical Cancer Research. 2012 Oct 15; 18(20): 5546-5553. PMID: 23071356.
Sedoris, K.C., Thomas, S.D., Clarkson, C.R., Muench, D., Islam, A., Singh, R., and Miller, D.M. Genomic c-MYC quadruplex DNA selectively kills leukemia. Molecular Cancer Therapeutics. 2012 Jan; 11(1): 66-76. PMID: 22084162.
Research Assistant III
Lab Phone: 513-636-6096
I received my Ph.D in Experimental Hematology at the Faculty of Medicine, Lund University in Sweden. In graduate work, I studied the function of the ETO corepressor homologues (ETO, MTG16 and MTGR1), in normal and malignant hematopoiesis. We found that the ETO homologues potentially have different roles in hematopoiesis, where they are involved in regulating progenitor maintenance and lineage differentiation.
As a Post Doc in the Grimes lab, I have focused on understanding myeloid lineage decisions during homeostasis. We first performed single cell RNA Seq on hematopoietic bone marrow stem and progenitor cells. Next, we collaborated with Nathan Salomonis in the Division of Bioinformatics to develop ICGS, a method for performing an unsupervised analysis of single cell RNA Seq data sets. You can look up any gene in our data set here.
We sampled mouse progenitor populations, analyzed them with our new approach, then validated the results using biological assays. We captured prevalent mixed- lineage intermediates undergoing “dynamic instability” (forming and unforming lineage decisions) and identified lineage specification factors Irf8 and Gfi1 act as key components of counteracting myeloid-gene-regulatory networks (Olsson et al., 2016). I am currently focused on understanding the molecular underpinnings of dynamically unstable states.
Olsson, A., M. Venkatasubramanian, V. K. Chaudhri, B. J. Aronow, N. Salomonis, H. Singh and H. L. Grimes (2016). Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature 537(7622): 698-702.
Goyama, S., J. Schibler, L. Cunningham, Y. Zhang, Y. Rao, N. Nishimoto, M. Nakagawa, A. Olsson, M. Wunderlich, K. A. Link, B. Mizukawa, H. L. Grimes, M. Kurokawa, P. P. Liu, G. Huang and J. C. Mulloy (2013). Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. J Clin Invest 123(9): 3876-3888.
Phelan, J. D., I. Saba, H. Zeng, C. Kosan, M. S. Messer, H. A. Olsson, J. Fraszczak, D. A. Hildeman, B. J. Aronow, T. Moroy and H. L. Grimes (2013). Growth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors. PLoS Genet 9(9): e1003713.
Taniguchi Ishikawa, E., K. H. Chang, R. Nayak, H. A. Olsson, A. M. Ficker, S. K. Dunn, M. N. Madhu, A. Sengupta, J. A. Whitsett, H. L. Grimes and J. A. Cancelas (2013). Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated beta1/beta2-integrin trafficking. Nat Commun 4: 1660.
Rehn, M., A. Olsson, K. Reckzeh, E. Diffner, P. Carmeliet, G. Landberg and J. Cammenga (2011). Hypoxic induction of vascular endothelial growth factor regulates murine hematopoietic stem cell function in the low-oxygenic niche. Blood 118(6): 1534-1543.
Olsson, A., I. Olsson and R. S. Dhanda (2008). Transcriptional repression by leukaemia-associated ETO family members can be independent of oligomerization and coexpressed hSIN3B and N-CoR. Biochim Biophys Acta 1779(10): 590-598.
Lindberg, S. R., A. Olsson, A. M. Persson and I. Olsson (2005). The Leukemia-associated ETO homologues are differently expressed during hematopoietic differentiation. Exp Hematol 33(2): 189-198.
Lindberg, S. R., A. Olsson, A. M. Persson and I. Olsson (2003). Interactions between the leukaemia-associated ETO homologues of nuclear repressor proteins. Eur J Haematol 71(6): 439-447.
H. Leighton Grimes, PhD
Phone: 513-636-6089Fax: 513-636-5355Email: email@example.com
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