Kenneth R. Peterson, Ph.D.

Director, Center for Epigenetics and Stem Cell Biology
Professor and Vice Chair
Department of Biochemistry and Molecular Biology

Ph.D., University of Arizona, 1987
Postdoctoral, University of Arizona, 1987-1990
Red blood cells carry oxygen to tissues and organs throughout the body and ferry waste carbon dioxide from them to the lungs for exhalation.  Hemoglobin is the molecule in red blood cells responsible for this transport and is comprised of two a-like globin chains, two b-like globin chains and four heme molecules.  Many diseases of red blood cells, termed hemoglobinopathies, have been described.  Sickle cell disease (SCD) affects red cell shape and renders them ineffective; resulting in anemia along with attendant complications.  SCD is gene-derived; that is, it is caused by a single point mutation in the coding sequence of the adult 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 human b-globin locus consists of five functional b-like globin genes, all of which serve as the b-chain in the hemoglobin molecule during different stages of development.  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 silenced in the adult.  Introducing an active fetal g-globin gene in the adult by bone marrow transplantation to substitute for a defective adult b-globin gene is one goal of current gene therapy efforts.  Realizing this goal requires understanding the molecular mechanisms that regulate globin gene switching.  Our laboratory is focused on the cis- and trans-control of human b-like globin gene expression during development; that is, the identification and characterization of DNA elements and transcription factors regulating globin synthesis via interaction of the proteins with these sequences.  A major regulatory motif of this class is the locus control region (LCR).  The mechanisms by which LCRs function are largely unknown, but it is becoming clear that they are important regulatory elements for developmental control of gene expression, not only for the b-globin locus, but for other mammalian loci as well.  Mechanisms underlying the developmental regulation of globin gene switching that are under analysis in the lab include: 1) the sequence determinants of LCR-globin gene interaction and their specificity, 2) the function of the LCR DNAse I-hypersensitive sites, 3) the physical structure of LCR-globin gene contacts, 4) the role of chromatin domain boundary elements within the b-globin locus, 5) g-globin gene silencing - identification of both cis-acting silencer sequences and repressor proteins, and 6) activation of g-globin gene expression - validation of putative, partially characterized protein activators, identification of novel transactivators, and testing of pharmacologic activators.  Experimental systems involve analysis of transgenic mice and cell lines produced with human b-globin locus yeast artificial chromosomes (b-YACs) as transgenes, as well as the ancillary bacterial and yeast molecular biology procedures necessary to generate these mice and cell lines.  In addition, we have established unique cell lines from the bone marrow and fetal liver of our b-YAC transgenic mouse lines using a novel system to enforce dimerization of growth signal transduction monomers into a functional molecule, resulting in multi-potential cell lines that proliferate, but do not differentiate.  These will be used to select for novel hereditary persistence of fetal hemoglobin (HPFH) mutations, fetal globin transactivator proteins and for screening small molecule inducers of g-globin gene expression.  A variety of cutting-edge molecular biology and biochemistry techniques are used to study cis-regulation, protein-DNA, and protein-protein interaction aspects of gene expression during development within these systems.

Selected Publications

Getman M., England S. J., Malik J., Peterson K.,  Palis J., and Steiner L. A..  2014.  Extensively self-renewing erythroblasts derived from transgenic β-YAC mice are a novel model system for studying globin switching and terminal erythroid maturation.  Exptl. Hematol. 42:536-546.e8. 

Peterson K. R., Costa F. C., Fedosyuk H.,  Neades R. Y, Chazelle A. M., Zelenchuk L., Fonteles A. H., Dalal P., Roy A. ,  Chaguturu R., Li B., and Pace B. S..  2014.  A cell-based high-throughput screen for novel inducers of fetal hemoglobin for treatment of hemoglobinopathies.  PLoS One 9:e107006. 

Zhang Z., Tan E. P., Peterson K. R. , and Slawson C. 2014. O-GlcNAcase expression is critical in maintaining O-GlcNAc cellular homeostasis.  Frontiers in Endocrinol. 5:206.   

Braghini, C. A., F. C. Costa, H. Fedosyuk, R. Y. Neades, L. V. Novikova, M. P. Parker, R. D. Winefield, and K. R. Peterson.  2016.  Generation of non-deletional hereditary persistence of fetal hemoglobin (HPFH) b-YAC transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH.  Exp. Biol. Med. (In press).

Costa, F. C., H. Fedosyuk, R. Neades, J. Bravo de los Rios, C. F. Barbas III, and K. R. Peterson.  (2012)  Induction of fetal hemoglobin in vivo mediated by a synthetic g-globin zinc finger activator.  Anemia 2012;2012:507894. doi: 10.1155/2012/507894. 

Peterson, K. R., H. Fedosyuk, and S. Harju-Baker.  (2012)  LCR 5' hypersensitive site specificity for globin gene activation within the active chromatin hub.  Nucleic Acids Res. 40:11256-11269. 

Costa, F. C., H. Fedosyuk, A. M. Chazelle, R. Y. Neades, and K. R. Peterson.  (2012)  Mi2b is required for g-globin gene silencing:  Temporal assembly of a GATA-1-FOG-1-Mi2 repressor complex in b-YAC transgenic mice.  PLoS Genet. 2012 Dec;8(12):e1003155. 

Giardine, B., J. Borg, D. R. Higgs, K. R. Peterson, S. Philipsen, D. Maglott, B. K. Singleton, D. J. Anstee, A. N. Basak, B. Clark, F. C. Costa, P. Faustino, H. Fedosyuk, A. E. Felice, A. Francina, M. V. E. Gallivan, M. Georgitsi, R. J. Gibbons, P. C. Giordano, C. L. Harteveld, J. D. Hoyer, P. Joly, E. Kanavakis, P. Kollia, S. Menzel, W. Miller, K. Moradkhani, J. Old, A. Papachatzopoulou, M. N. Papadakis, P. Papadopoulos, S. Pavlovic, M. Radmilovic, C. Riemer, I. Schrijver, M. Stojiljkovic, S. L. Thein, J. Traeger-Synodinos, R. Tully, T. Wada, J. Waye, C. Wiemann, B. Zukic, D. H. K. Chui, H. Wajcman, R. C. Hardison, and G. P. Patrinos.  (2011)  Systematic documentation of human genetic variation using the microattribution approach.  Nature Genet. 43:295-301.

Steenhard, B. M., A. Zelenchuk, L. Stroganova, K. Isom, P. L. St. John, G. K. Andrews, K. R. Peterson, and D. R. Abrahamson.  (2011)  Transgenic expression of human LAMA5 suppresses murine Lama5 mRNA and Laminin a5 protein deposition.  PLoS ONE 6:e23926.

Banzon V, Ibanez V, Vaitkus K, Ruiz MA, Peterson K, DeSimone J, Lavelle D. (2011) siDNMT1 increases γ-globin expression in chemical inducer of dimerization (CID)-dependent mouse βYAC bone marrow cells and in baboon erythroid progenitor cell cultures. Exp Hematol.39:26-36.e1.

Last modified: Feb 01, 2016

Kenneth R. Peterson, Ph.D.


Kenneth R. Peterson, Ph.D.
Director, Center for Epigenetics and Stem Cell Biology
Professor and Vice Chair