Professor and Vice Chairman3901 Rainbow Boulevard
4034 WHE
Kansas City, KS 66160
Phone: (913) 588-6907
Fax: (913) 588-7440
Email: kpeterson@kumc.edu
Ph.D., University of Arizona, 1987; Postdoctoral, University of Washington, Seattle, Washington
Red blood cells ferry oxygen and carbon dioxide throughout the body. Sickle cell disease, which impacts one of 500 African Americans born each year, affects their shape and renders them ineffective, resulting in anemia. Sickle cell disease is a genetic disease; it is caused by a single point mutation in the coding sequence of the b-globin gene. A second disease of these cells, b-thalassemia, also causes anemia. b-thalassemias result from an array of mutations in the b-globin locus that affect b-globin gene function. Gene therapy could aid in the replacement of the mutant globin gene and help cure these disorders. The b-globin locus consists of five functional b-like globin genes.
The e-globin gene is expressed in the primitive yolk sac during the first six weeks of gestation; the Gg- and Ag-globin genes are transcribed in the fetal liver from the sixth week to shortly after birth; and the b-globin gene (and to a much lesser extent the d-globin gene) is expressed in bone marrow soon after birth for the duration of life. The e-globin and g-globins are largely silenced in the adult. Introducing an active fetal g-globin gene in the adult by bone marrow transplantation or transactivation of g-globin gene expression are goals of current gene therapy efforts towards curing sickle cell disease and b-thalassemias.
Realizing these goals requires understanding the molecular mechanisms controlling globin gene switching and the Peterson laboratory seeks to unravel the regulatory motifs involved, particularly as they pertain to transactivation or pharmacologic induction of fetal g-globin synthesis. In addition, Dr. Peterson’s laboratory is focused on the cis-control of human b-like globin gene expression during development; that is, the identification and characterization of DNA elements regulating globin synthesis via interaction of these sequences with trans-acting proteins.
One of the most challenging questions in developmental biology concerns the mechanisms by which cis-regulatory elements/regions within a gene locus confer distinct developmental-specific expression patterns during ontogeny. The cis motifs under study include, but are not limited to, individual gene associated sequences involved in activation, silencing and competition for interaction with the locus control region (LCR), gene order, distance from the LCR, intergenic sequences such as domain boundaries or barriers, and chromatin architecture. Acquisition of knowledge about these processes may aid in the development of targeted therapies or therapeutics.
Navas, P.A., Peterson, K.R., Li, Q., McArthur, M., and Stamatoyannopoulos, G. (2001) The 5’HS4 core element of the human ß-globin locus control region is required for high level b-globin gene expression in definitive erythroid cells. J. Mol. Biol. 312, 17-26.
Navas, P.A., Li, Q., Peterson, K.R., Swank, R.A., Rohde, A., Roy, J., and Stamatoyannopoulos, G. (2002) Activation of the b-like globin genes is dependent on the presence of the b-locus control region. Human Mol. Genet. 11, 893-903.
Harju, S.J., McQueen, K.J., and Peterson, K.R. (2002) Chromatin structure and control of b-like globin gene switching. Exptl. Biol. Med. 227, 683-700.
Peterson, K.R. (2003) Hemoglobin switching: new insights. Curr. Opin. Hematol. 10, 123-129.
Navas, P.A., Swank, R., Yu, M., Peterson, K.R., and Stamatoyannopoulos, G. (2003) Mutation of a transcriptional motif of a distant regulatory element reduces the expression of embryonic and fetal globin genes. Human Mol. Genet. 12, 2941-2948.
Li, Q., Peterson, K.R., Fang, X., and Stamatoyannopoulos, G. (2002) Locus control regions. Blood 100, 3077-3086.
Peterson, K.R. (2003) Transgenic mice carrying yeast artificial chromosomes. Expert Rev. Molec. Med. 5, 1-25.
Rodova, M., M. R. Islam, K. R. Peterson, and J. P. Calvet. (2003) Remarkable sequence conservation of a small intron in the PKD1 gene. Mol. Biol. Evol. 20:1669-1674.
Peterson, K.R., Fedosyuk, H., Zelenchuk, L., Nakamoto, B., Yannaki, E., Stamatoyannopoulos, G., Ciciotte, S., Peters, L.L., Scott, L.M., and Papayannopoulou, T. (2004) Transgenic Cre expression mice for generation of erythroid-specific gene alterations. Genesis 39, 1-9.
Harju, S. J., H. Fedosyuk, and K. R. Peterson. (2004) Rapid isolation of yeast genomic DNA: Bust n’ Grab. MCB Biotechnol. 4:8-13.
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The University of Kansas Medical Center