Assistant Professor, Biochemistry and Molecular Biology
Phone: 402-559-4467 (Office)
Bachelors of Arts, Biology Major, Washington University in St. Louis
Ph. D., Cellular and Molecular Biology, University of Wisconsin- Madison
Student research opportunities in my lab:
Interested students should contact Dr. Hyde.
Primary Research/Clinical Interests/Expertise:
Regulation of gene expression in leukemia and normal hematopoiesis
Leukemia is often characterized by the presence of specific, recurrent chromosomal abnormalities that generate novel fusion genes. In the Hyde lab, we study a subtype of Acute Myeloid Leukemia (AML) that is caused by an inversion of chromosome 16 (Inv(16)). This inversion generates a fusion gene between the transcription factor CBFB and the gene for Smooth Muscle Myosin Heavy Chain, MYH11, to generate CBFB-MYH11, which encodes the protein CBFβ-SMMHC. It is known that expression of the fusion protein is the initiating event in leukemogenesis, but its mechanism is currently not well understood.
Recent evidence suggests that CBFβ-SMMHC acts with its dimerization partner, the transcription factor RUNX1, to induce changes in gene expression that block normal myeloid differentiation and induce a population of leukemia initiating cells (LICs). The LICs are the cells that must acquire additional mutations in order to transform into a frank leukemia. After leukemic transformation, the LICs are thought to be the cells responsible for relapse of the disease, so are of considerable clinical relevance.
Using tissue culture and mouse models of Inv(16) AML, the Hyde lab is focused on better understanding the LIC population and the critical gene expression changes that lead to their induction and survival. This work has the potential to identify new targets for drug development for the treatment of Inv(16) AML, as well as mechanisms important in other AML subtypes and normal myeloid differentiation.
Hyde RK, Zhao L, Alemu L, Liu PP. Runx1 is required for Cbfb-MYH11 activity in embryonic hematopoiesis and leukemogenesis. Manuscript in preparation.
Hyde RK*, Kamikubo Y*, Zhao L*, Alemu L, Rivas C, Garrett LJ, Liu PP. The C-terminus of CBFb-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis. Blood. 2013 Jan 24; 121(4):638-42.PMID: 23152542 PMCID: PMC3557645
*These authors contributed equally to this work.
Cunningham L, Finckbeiner S, Hyde RK, Southall N, Marugan J, Yedavalli V, Dehdashti S, Reinhold W, Alemu L, Yeh JRJ, Sood R, Pommier Y, Austin C, Jeang KT, Zheng W, Liu PP. Inhibition of RUNX1-CBFb interaction by benzodiazepine Ro5-3335 as a target therapy for CBF leukemias. PNAS. 2012 Sep 4;1-9(36):14592-7.PMID: 22912405 PMCID: PMC3437880
Y, Zhao L, Wunderlich M, Hyde RK, Garrett L, Compton S, Bushweller J, Mulloy JC, Liu PP. Leukemogenesis by truncated CBFb-SMMHC defective in high-affinity binding with RUNX1. Cancer Cell. 2010 May 18; 17(5):455-68.PMID: 20478528 PMCID: PMC2874204
Hyde RK, Kamikubo Y, Alemu L, Anderson S, Kirby M, Zhao L, Liu PP. Cbfb/Runx1-repression independent blockage of differentiation and accumulation of Csf2rb expressing cells by Cbfb-MYH11. Blood. 2010 Feb 18:115(7):1433-43.PMID: 20007544 PMCID: PMC2826765
Khan M, Hyde RK, Dutra A, Mohide P, Liu P. Core binding factor beta (CBFB) haploinsufficiency due to an interstitial deletion at 16q21p22 resulting in delayed cranial ossification, cleft palate, congenital heart anomalies, and feeding difficulties but favorable outcome. Am J Med Genet A. 2006 Oct 4.PMID: 17022082
Balsitis S, Dick F, Farrell L, Lee D, Hyde RK, Griep AE, Dyson N, Lambert PF. Examination of the pRb-dependent and pRb-independent functions of E7 in vivo. J. of Virology 2005 Sep;79(17):11392-402.PMID: 16103190 PMCID: PMC1193607
Hyde RK, Griep AE. Unique roles for E2F1 in the mouse lens in the absence of functional pRB proteins. Invest Ophthalmol Vis Sci. 2002 May;43(5):1509-16.PMID: 11980867
Ben-Menahem D, Jablonka-Shariff A, Hyde RK, Pixley MR, Srivastava S, Berger P, Boime I. The position of the alpha and beta subunits in a single chain variant of human chorionic gonadotropin affects the heterodimeric interaction of the subunits and receptor-binding epitopes. J Biol Chem. 2001 Aug 10;276(32):29871-9.PMID: 11390409
Ben-Menahem D, Hyde RK, Pixley MR, Berger P, Boime I. Synthesis of multi-subunit domain gonadotropin complexes: a model for alpha/beta heterodimer formation. Biochemistry. 1999 Nov 16; 38(46): 15070-7.PMID: 10563789
Hyde RK, Liu PP. Germline Pax5 mutations and B cell leukemia. Nat Genet. 2013 September 26; 45(10):1104-5. PMID 24071841.
Hyde RK, Liu PP. GATA2 mutations lead to MDS and AML. Nat Genet. 2011 September 28;43(10):926-7.PMID: 21956389
Hyde RK, Liu PP. The role of microRNAs in acute myeloid leukemia. F1000 Biol Rep. 2010 November 24;2:81.PMID: 21170374 PMCID: PMC2998852
Hyde RK, and P. Paul Liu. RUNX1 repression-independent mechanisms of leukemogenesis by fusion genes CBFB-MYH11 and AML1-ETO (RUNX1-RUNX1T1). Journal of Cellular Biochemistry. 2010 August 1;110(5)1039-45.PMID: 20589720 PMCID: PMC3298446