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Department of Biochemistry & Molecular Biology  :  Faculty  :  Kenneth Peterson, Ph.D.

Kenneth Peterson, Professor

Kenneth PetersonDepartment of Biochemistry and Molecular Biology

University of Kansas Medical Center
913-588-6907
kpeterson@kumc.edu

Education & Experience

  • Northern Arizona University, B.S., Microbiology, Chemistry, 1979
  • Idaho State University, M.S., 1981
  • University of Arizona, Ph.D., 1987
  • University of Washington, Seattle, Washington, Research Assistant Professor of Medicine, Division of Medical Genetics, Department of Medicine, 1992-1996
  • University of Washington, Seattle, Washington, Adjunct Research Assistant Professsor of Genetics, Department of Genetics, 1996
  • University of Washington, Seattle, Washington, Adjunct Research Associate Professor of Medicine, Division of Medical Genetics, Department of Mediciine, 1996-1998
  • University of Washington, Seattle, Washington, Adjunct Research Associate Professor of Genetics, Department of Genetics, 1996-1998
  • University of Kansas Medical Center, Kansas City, Kansas, Associate Professor of Biochemistry and Molecular Biology, Department of Biochemistry and Molecular Biology, 1998-present
  • University of Kansas Medical Center, Kansas City, Kansas, Associate Professor of Anatomy and Cell Biology, Department of Anatomy and Cell Biology, 1998-present
  • University of Kansas Medical Center, Kansas City, Kansas, Associate Professor, Department of Biochemistry and Molecular Biology and Department of Anatomy and Cell Biology, 1998-2003
  • University of Kansas Medical Center, Kansas City, Kansas, Vice-Chairman, Department of Biochemistry and Molecular Biology, 2003-present
  • University of Kansas Medical Center, Kansas City, Kansas, Professor, Department of Biochemistry and Molecular Biology and Department of Anatomy and Cell Biology, 2003-present

Major Research Interest

My major interest is genetic regulatory mechanisms with emphasis on the delineation of the function of locus control regions (LCRs). The human beta-globin locus serves as our primary model system. This locus consists of 5 functional genes arrayed in their order of expression during development, 5'-epsilon-Ggamma-Agamma-delta-beta-3'. The LCR is located 6- to 20-Kb upstream of the epsilon-globin gene. It is composed of five DNAseI-hypersensitive sites (HSs), which are highly conserved during evolution. The globin LCR has multiple properties, including the activation and maintenance of open chromatin domains, insulation from the effects of surrounding negative chromatin, conference of erythroid cell lineage specificity on globin gene expression and enhancement of globin gene transcription. LCRs or LCR-type elements have been identified in over 30 mammalian loci, but they are less understood compared to the beta-globin locus LCR. The mechanism of action of the LCR remains unknown.

Questions that I am pursuing include the structure/function relationships of the individual HSs composing the LCR, the structural features that are required for formation of the LCR holocomplex, the mechanism of interaction between the LCR and individual globin genes, and the mechanism whereby the LCR activates chromosomal domains. In my studies, I utilize yeast artificial chromosomes containing the entire beta-globin locus (beta-YACs). Mutations are introduced into the beta-YACs by homologous recombination in yeast without leaving exogenous DNA; the YACs are purified and microinjected into murine oocytes for the production of transgenic mice or transfected into established cell lines. Thus, the effect of these mutations on LCR function may be analyzed in the context of the intact beta-globin locus throughout development. I also study other genetic regulatory mechanisms and disease pathogenesis using transgenic mouse models of sickle cell disease, Alzheimer's disease, Kennedy's disease, polycystic kidney disease and Alport's syndrome.

Representative Publications

Blau, C. A., C. F. Barbas, III, A. Bomhoff, R. Neades, J. Yan, P. A. Navas, and K. R. Peterson.  2005.  γ-globin gene expression in CID-dependent multi-potential cells established from b-YAC transgenic mice.  J. Biol. Chem. (In press). 

Harju, S. J., P. A. Navas, G. Stamatoyannopoulos, and K. R. Peterson.  2005.  Genome architecture of human b-globin locus affects developmental regulation of gene expression.  Mol. Cell. Biol. (In press). 

Karpova, T., J. Presley, R. R. Manimaran, S. P. Scherrer, L. Tajeda, K. R. Peterson, and L. L. Heckert.  2005.  A Ftz-F1-containing yeast artificial chromosome recapitulates expression of steroidogenic factor 1 in vivo.  Molec. Endocrinol. (In press).  

Fang, X., J. Sun, P. Xiang, M. Yu, P. A. Navas, K. R. Peterson, G. Stamatoyannopoulos, and Q. Li.  2005.  Synergistic and additive properties of the b-globin LCR revealed by 5'HS3 deletion mutations: Implication on LCR chromatin architecture.  Mol. Cell. Biol. 25:7033-7041. 

Harju, S. J., H. Fedosyuk, and K. R. Peterson.  2004.  Rapid isolation of yeast genomic DNA:  Bust n’ Grab.  MCB Biotechnol. 4:8-13. 

Peterson, K. R., H. Fedosyuk, L. Zelenchuk, B. Nakamoto, E. Yannaki, G. Stamatoyannopoulos, S. Ciciotte, L. L. Peters, L. M. Scott, and T. Papayannopoulou.  2004.  Transgenic Cre expression mice for generation of erythroid-specific gene alterations.  Genesis 39:1-9. 

Peterson, K. R.  2003.  Hemoglobin switching:  New insights.  Curr. Opin. Hematol. 10:123-129. 

Navas, P. A., R. Swank, M. Yu, K. R. Peterson, and G. Stamatoyannopoulos.  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. 

Peterson, K. R.  2003.  Hemoglobin switching:  looping along.  BloodMed.com December 24, 2003. 

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.

Harju, S. J., K. J. McQueen, and K. R. Peterson.  2002.  Chromatin structure and control of b-like globin gene switching.  Exptl. Biol. Med. 227:683-700.

Li, Q., K. R. Peterson, X. Fang, and G. Stamatoyannopoulos.  2002.  Locus control regions.  Blood 100:3077-3086.

Navas, P.S., Li, G., Peterson, K.R., Swank, R.A., Rohde, A., Roy, J., and Stamatoyannopoulos.  2002.  Activation of the ß-like globin genes is dependent on the presence of the ß-locus control regions.  Human. Mol. Genet.  11:893-903.

Navas, P.S., K.R. Peterson, G.Li, M. McArthur and G. Stamatoyannopoulos.  2001.  The 5'HS4 core element of the human ß-globin locus control region is required for high level ß-globin gene expression in definitive erythroid cells.  J. Mol.Biol.  312:17-26.

Perkins, A.C., K.R. Peterson, G. Stamatoyannopoulos, H.E. Witkowska and S.H. Orkin.  2000.  Fetal expression of a human  Agamma  globin transgene rescues globin chain imbalance but not hemolysis in EKLF null mouse embryos.  Blood. 95:1827-1833.

Papayannopoulou, T., G.V. Priestly, A. Rohde, K.R. Peterson and B. Nakamoto.  2000.  Hemopoietic lineage commitment decisions:  In vivo evidence from a transgenic mouse model harboring µLCR-ßpro-lacZ as a transgene.  Blood. 95: 1274-1282.

Vassilopoulos, G., P. A. Navas, E. Skarpidi, K. R. Peterson, C. H. Lowrey, T. Papayannopoulou, and G. Stamatoyannopoulos. 1999. Correct function of the locus control region may require passage through a nonerythroid cellular environment. Blood 93:703-712.

Peterson, K. R., P. A. Navas, Q. Li, and G. Stamatoyannopoulos. 1998. LCR-dependent gene expression in b-globin YAC transgenics: Detailed structural studies validate functional analysis even in the presence of fragmented YACs. Human Mol. Genet. 7:2079-2088.

Navas, P. A., K. R. Peterson, Q. Li, E. Skarpidi, A. Rohde, S. E. Shaw, C. H. Clegg, H. Asano, and G. Stamatoyannopoulos. 1998. Developmental specificity of the interaction between the locus control region and embryonic or fetal globin genes in transgenic mice with an HS3 core deletion. Mol. Cell. Biol. 18:4188-4196.

La Spada, A. R., K. R. Peterson, S. A. Meadows, M. E. McClain, G. Jeng, R. S. Chmelar, H. A. Haugen, K. Chen, M. J. Singer, D. Moore, B. J. Trask, K. H. Fischbeck, C. H. Clegg, and G. S. McKnight. 1998. Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability. Human Mol. Genet. 7:959-967.

Blau, C. A., K. R. Peterson, J. G. Drachman, and D. Spencer. 1997. A proliferative switch for genetically modified cells. Proc. Natl. Acad. Sci. USA 94:3076-3081.

Li, Q., C. Clegg, K. Peterson, N. Raich, and G. Stamatoyannopoulos. 1997. Regulation of the human b-globin locus by human GATA-1 as measured in a binary transgenic mouse model. Proc. Natl. Acad. Sci. USA 94:2444-2448.

Peterson, K. R., C. H. Clegg, P. A. Navas, E. J. Norton, T. G. Kimbrough, and G. Stamatoyannopoulos. 1996. Effect of deletion of 5’HS3 or 5’HS2 of the human b-globin locus control region on the developmental regulation of globin gene expression in b-globin locus yeast artificial chromosome transgenic mice. Proc. Natl. Acad. Sci. USA 93:6605-6609.

Loring, J. F., C. Paszty, A. Rose, T. K. McIntosh, H. Murai, J. E. S. Pierce, S. R. Schramm, E. M. Rubin, V. M.-Y. Lee, J. Q. Trojanowski, and K. R. Peterson. 1996. Rational design of an animal model for Alzheimer’s disease: Introduction of multiple human genomic transgenes to reproduce AD pathology in a rodent. Neurobiol. Aging 17:173-182.

Peterson, K. R., Q. Li, C. H. Clegg, T. Furukawa, P. A. Navas, E. J. Norton, T. G. Kimbrough, and G. Stamatoyannopoulos. 1995. Use of yeast artificial chromosomes (YACs) in studies of mammalian development: Production of b-globin locus mice carrying human globin developmental mutants. Proc. Natl. Acad. Sci. USA 92:5655-5659.

Zitnik, G., K. R. Peterson, G. Stamatoyannopoulos, and T. Papayannopoulou. 1995. Effects of butyrate and glucocorticoids on g to b globin gene switching in somatic cell hybrids. Mol. Cell. Biol. 15:790-795.

Peterson, K. R., G. Zitnik, C. Huxley, C. H. Lowrey, A. Gnirke, K. A. Leppig, T. Papayannopoulou, and G. Stamatoyannopoulos. 1993. Use of YACs for studying control of gene expression: Correct regulation of the genes of a human b-globin locus YAC following transfer to mouse erythroleukemia cell lines. Proc. Natl. Acad. Sci. USA 90:11207-11211.

Peterson, K. R. and G. Stamatoyannopoulos. 1993. Role of gene order in the developmental control of human g and b globin gene expression. Mol. Cell. Biol. 13:4836-4843.

Peterson, K. R., C. H. Clegg, C. Huxley, B. M. Josephson, H. S. Haugen, T. Furukawa, and G. Stamatoyannopoulos. 1993. Transgenic mice containing a 248 kb human b locus yeast artificial chromosome display proper developmental control of human globin genes. Proc. Natl. Acad. Sci. USA 90:7593-7597.

Gnirke, A., C. Huxley, K. Peterson, and M. V. Olson. 1993. Microinjection of intact 200-500 kb fragments of YAC DNA into mammalian cells. Genomics 15:659-667.