Pamela Geyer, PhD

Portrait
Professor of Biochemistry
Professor of Obstetrics and Gynecology

Contact Information

Primary Office: 3135E MERF
Iowa City, IA 52242
319-335-6953

Education

BS, McGill University
PhD, Ohio State University

Post Doctoral Fellow, Dept of Biology, Johns Hopkins University
Post Doctoral Fellow, Dept of Biology, Johns Hopkins University

Education/Training Program Affiliations

Department of Biochemistry PhD, Interdisciplinary Graduate Program in Genetics, Interdisciplinary Graduate Program in Molecular and Cellular Biology, Interdisciplinary Graduate Program in Neuroscience, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Center, Program and Institute Affiliations

Institute for Clinical and Translational Science

Research Summary

The Geyer laboratory is interested in understanding mechanisms involved in genome organization and gene regulation. Two areas are currently being studied, insulators and nuclear lamina function. Insulators are a specialized class of DNA regulatory elements that have a conserved role in chromosome organization, dividing chromosomes into independent functional domains. These elements shelter genes from the surrounding positive and negative regulatory effects by blocking interactions between enhancers, silencers and promoters. Such properties have made insulators favorable candidates to improve strategies for gene therapy. While gene therapy is a promising technology that delivers therapeutic genes to a target tissue, successful application of this approach faces many challenges, including the cross regulation of endogenous genes by DNA regulatory elements in the vector. Insulators may prevent such undesirable effects. Studies in the Geyer lab include determination of the molecular mechanisms used by insulators to prevent interactions between enhancers, silencers and promoters and the identification of novel insulators. Combinations of insulators that employ different regulatory mechanisms may provide optimal protection of transgenes from the position effects of the surrounding chromatin and prevent sequences in the vector from mis-regulating endogenous genes at the site of genomic insertion. As such, insights into insulator mechanisms will allow advances in improving strategies for gene therapy and treatment of human disease. The nuclear lamina is an extensive protein network that lines the inner surface of the nuclear membrane. This network consists of intermediate filament proteins, called lamins, and associated inner nuclear membrane proteins, such as the LEM domain proteins. LEM domain genes make essential contributions to the function of the lamina, as mutations in these genes cause human diseases, known as laminopathies. For example, mutations in the genes that encode emerin and MAN1 cause Emery-Dreifuss Muscular Dystrophy and Buschke-Ollendorf Syndrome, respectively. Interestingly, these diseases are associated with tissue-specific pathologies, even though LEM domain genes are broadly expressed. To understand mechanisms underlying such human diseases, the Geyer lab is investigating the role of LEM domain proteins in lamina function, using Drosophila as a model organism. A molecular genetic approach is being taken to determine the contributions that individual LEM domain proteins make to nuclear lamina function.

Publications

Baxley, R. M., Bullard, J. D., Klein, M. W., Fell, A. G., Morales-Rosado, J. A., Duan, T., Geyer, P. K. (2017). Deciphering the DNA code for the function of the Drosophila polydactyl zinc finger protein Suppressor of Hairy-wing. Nucleic Acids Research, 45(8), 4463-4478. DOI: 10.1093/nar/gkx040.

Berger, F., Geyer, P. K. (2016). Editorial overview: Genome architecture and expression: Connecting genome composition and nuclear architecture with function. (Vols. 37). pp. iv-vi. Current opinion in genetics & development. PMID: 27292868.

Barton, L. J., Lovander, K. E., Pinto, B. S. & Geyer, P. K. (2016). Drosophila male and female germline stem cell niches require the nuclear lamina protein Otefin. Developmental biology, 415(1), 75-86. PMID: 27174470.

Barton, L. J., Soshnev, A. A. & Geyer, P. K. (2015). Networking in the nucleus: a spotlight on LEM-domain proteins. Current opinion in cell biology, 34, 1-8. PMID: 25863918.

Barton, L. J., Geyer, P. K. (2014). Stacking the deck for the next generation. (Vols. 81). pp. 481. Molecular Reproduction and Development.

Barton, L. J., Wilmington, S. R., Martin, M. J., Skopec, H. M., Lovander, K. E., Pinto, B. S. & Geyer, P. K. (2014). Unique and shared functions of nuclear lamina LEM domain proteins in Drosophila. Genetics, 197(2), 653-65. PMID: 24700158.

Barton, L. J., Pinto, B. S., Wallrath, L. L. & Geyer, P. K. (2013). The Drosophila nuclear lamina protein otefin is required for germline stem cell survival. Developmental cell, 25(6), 645-54. PMID: 23806619.

Soshnev, A. A., Baxley, R. M., Manak, J. R., Tan, K. & Geyer, P. K. (2013). The insulator protein Suppressor of Hairy-wing is an essential transcriptional repressor in the Drosophila ovary. Development, 140(17), 3613-23. PMID: 23884443.

Hohl, A. M., Thompson, M., Soshnev, A. A., Wu, J., Morris, J., Hsieh, T. S., Wu, C. T. & Geyer, P. K. (2012). Restoration of topoisomerase 2 function by complementation of defective monomers in Drosophila. Genetics, 192(3), 843-56. PMID: 22923380.

Shoshnev, A. A., He, B., Baxley, R. M., Jiang, N., Hart, C. M., Tan, K. & Geyer, P. K. (2012). Genome-wide studies of the multi-zinc finger Drosophila Suppressor of Hairy-wing protein in the ovary. Nucleic Acids Research, 40(12). PMID: 22406832.

Baxley, R. M., Soshnev, A. A., Koryakov, D. E., Zhimulev, I. F. & Geyer, P. K. (2011). The role of the Suppressor of Hairy-wing insulator protein in Drosophila oogenesis. Developmental biology, 356(2), 398-410. PMID: 21651900.

Soshnev, A. A., Ishimoto, H., McAllister, B. F., Li, X., Wehling, M. D., Kitamoto, T. & Geyer, P. K. (2011). A conserved long noncoding RNA affects sleep behavior in Drosophila. Genetics, 189(2), 455-68. PMID: 21775470.

Geyer, P. K., Vitalini, M. W. & Wallrath, L. L. (2011). Nuclear organization: taking a position on gene expression. Current opinion in cell biology, 23(3), 354-9. PMID: 21450447.

Dialynas, G., Speese, S., Budnik, V., Geyer, P. K. & Wallrath, L. L. (2010). The role of Drosophila Lamin C in muscle function and gene expression. Development (Cambridge, England), 137(18), 3067-77. PMID: 20702563.

Schulze, S. R., Curio-Penny, B., Speese, S., Dialynas, G., Cryderman, D. E., McDonough, C. W., Nalbant, D., Petersen, M., Budnik, V., Geyer, P. K. & Wallrath, L. L. (2009). A comparative study of Drosophila and human A-type lamins. PloS one, 4(10), e7564. PMID: 19855837.

Baxley, R. M., Geyer, P. K. (2008). The role of insulators in genome organization and gene expression. The Encyclopedia of Life Sciences, John Wiley & Sons.

Wallrath, L. L., Nagy, P. L. & Geyer, P. K. (2008). Epigenetics of development and human disease. (Vols. 647). pp. 1-2. Mutation research. PMID: 18983859.

Wallrath, L. L., Nagy, P. L., Geyer, P. K. (2008). Editorial. Epigenetics of Development and Human Disease. Mutation Research, 1(647), 1-2. PMID: 18983859.

Pinto, B. S., Wilmington, S. R., Hornick, E. E., Wallrath, L. L. & Geyer, P. K. (2008). Tissue-specific defects are caused by loss of the Drosophila MAN1 LEM domain protein. Genetics, 180(1), 133-45. PMID: 18723885.

Kuhn-Parnell, E. J., Helou, C., Marion, D. J., Gilmore, B. L., Parnell, T. J., Wold, M. S. & Geyer, P. K. (2008). Investigation of the properties of non-gypsy suppressor of hairy-wing-binding sites. Genetics, 179(3), 1263-73. PMID: 18562648.

Soshnev, A. A., Li, X., Wehling, M. D. & Geyer, P. K. (2008). Context differences reveal insulator and activator functions of a Su(Hw) binding region. PLoS genetics, 4(8), e1000159. PMID: 18704163.

Golovnin, A., Mazur, A., Kopantseva, M., Kurshakova, M., Gulak, P. V., Gilmore, B. L., Whitfield, W., Geyer, P. K., Pirrotta, V. & Georgiev, P. (2007). Integrity of the Mod(mdg4)-67.2 BTB domain is critical to insulator function in Drosophila. Molecular and cellular biology, 27, 963-974. PMID: 17101769.

Geyer, P. K., Wallrath, L. L. (2007). Heterochromatin: not just for silencing anymore: report of the Eighth International Conference on Drosophila Heterochromatin. Fly, 1(4), 251-6. PMID: 18820453.

Wallrath, L. L., Geyer, P. K. (2006). TFIIIC boxes in the genome. Cell, 125(5), 829-31. PMID: 16751090.

Drapeau, M. D., Cyran, S. A., Viering, M. M., Geyer, P. K. & Long, A. D. (2006). A cis-regulatory sequence within the yellow locus of Drosophila melanogaster required for normal male mating success. Genetics, 172(2), 1009-30. PMID: 16272418.

Parnell, T. J., Kuhn, E. J., Gilmore, B. L., Helou, C., Wold, M. S. & Geyer, P. K. (2006). Identification of genomic sites that bind the Drosophila suppressor of Hairy-wing insulator protein. Molecular and cellular biology, 26(16), 5983-93. PMID: 16880510.

Schulze, S. R., Curio-Penny, B., Li, Y., Imani, R. A., Rydberg, L., Geyer, P. K. & Wallrath, L. L. (2005). Molecular genetic analysis of the nested Drosophila melanogaster lamin C gene. Genetics, 171(1), 185-96. PMID: 15965247.

Kuhn, E. J., Hart, C. M. & Geyer, P. K. (2004). Studies of the role of the Drosophila scs and scs' insulators in defining boundaries of a chromosome puff. Molecular and cellular biology, 24(4), 1470-80. PMID: 14749365.

Wallrath, L. L., Danzer, J. R., Yazgan, O. & Geyer, P. K. (2004). Nuclear organization, chromatin structure and gene silencing. in Encyclopedia of Biological Chemistry, Elsevier, Oxford, 3, 105-108.

Kuhn, E. J., Viering, M. M., Rhodes, K. M. & Geyer, P. K. (2003). A test of insulator interactions in Drosophila. The EMBO journal, 22(10), 2463-71. PMID: 12743040.

Parnell, T. J., Grade, S. K., Geyer, P. K. & Wallrath, L. L. (2003). Position-effect variegation in human genetic disease. Encyclopedia of the Human Genome. John Wiley & Sons, Ltd, 4, 642-46.

Kuhn, E. J., Geyer, P. K. (2003). Genomic insulators: connecting properties to mechanism. Current opinion in cell biology, 15(3), 259-65. PMID: 12787766.

Parnell, T. J., Viering, M. M., Skjesol, A., Helou, C., Kuhn, E. J. & Geyer, P. K. (2003). An endogenous suppressor of hairy-wing insulator separates regulatory domains in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 100(23), 13436-41. PMID: 14597701.

Chen, J. L., Huisinga, K. L., Viering, M. M., Ou, S. A., Wu, C. T. & Geyer, P. K. (2002). Enhancer action in trans is permitted throughout the Drosophila genome. Proceedings of the National Academy of Sciences of the United States of America, 99(6), 3723-8. PMID: 11904429.

Geyer, P. K., Clark, I. (2002). Protecting against promiscuity: the regulatory role of insulators. Cellular and molecular life sciences : CMLS, 59(12), 2112-27. PMID: 12568337.

Roseman, R. R., Morgan, K., Mallin, D. R., Roberson, R., Parnell, T. J., Bornemann, D. J., Simon, J. A. & Geyer, P. K. (2001). Long-range repression by multiple polycomb group (PcG) proteins targeted by fusion to a defined DNA-binding domain in Drosophila. Genetics, 158(1), 291-307. PMID: 11333237.

Kuhn, E., Geyer, P. K. (2001). Boundary Elements. Encyclopedia of Molecular Medicine, John Wiley & Sons.

Geyer, P. K., Parnell, T. J. (2001). Chromosomes: Higher order organization. Encyclopedia of Life Sciences. London: Naturing Publishing Group.

Parnell, T. J., Geyer, P. K. (2000). Differences in insulator properties revealed by enhancer blocking assays on episomes. The EMBO journal, 19(21), 5864-74. PMID: 11060037.

Morris, J. R., Chen, J. L., Filandripos, S. T., Dunn, R. C., Fisk, R., Geyer, P. K. & Wu, C. T. (1999). An Analysis of Transvection at the yellow locus of Drosophila melanogaster. Genetics,(151), 633-651.

Morris, J. R., Chen, J., Filandrinos, S. T., Dunn, R. C., Fisk, R., Geyer, P. K. & Wu, C. (1999). An analysis of transvection at the yellow locus of Drosophila melanogaster. Genetics, 151(2), 633-51. PMID: 9927457.

Morris, J. R., Geyer, P. K. & Wu, C. T. (1999). Core promoter elements can regulate transcription on a separate chromosome in trans. Genes & development, 13(3), 253-8. PMID: 9990850.

Scott, K. C., Taubman, A. D. & Geyer, P. K. (1999). Enhancer blocking by the Drosophila gypsy insulator depends upon insulator anatomy and enhancer strength. Genetics, 153(2), 787-98. PMID: 10511558.

Morris, J. R., Chen, J. L., Geyer, P. K. & Wu, C. T. (1998). Two modes of transvection: enhancer action in trans and bypass of a chromatin insulator in cis. Proceedings of the National Academy of Sciences of the United States of America, 95(18), 10740-5. PMID: 9724774.

Mallin, D. R., Myung, J. S., Patton, J. S. & Geyer, P. K. (1998). Polycomb group repression is blocked by the Drosophila suppressor of Hairy-wing [su(Hw)] insulator. Genetics, 148(1), 331-9. PMID: 9475743.

Geyer, P. K. (1997). The role of insulator elements in defining domains of gene expression. Current opinion in genetics & development, 7(2), 242-8. PMID: 9115431.

Nagoshi, R. N., Patton, J. S., Bae, E. & Geyer, P. K. (1995). The somatic sex determines the requirement for ovarian tumor gene activity in the proliferation of the Drosophila germline. Development (Cambridge, England), 121(2), 579-87. PMID: 7768194.

Rodesch, C., Geyer, P. K., Patton, J. S., Bae, E. & Nagoshi, R. N. (1995). Developmental analysis of the ovarian tumor gene during Drosophila oogenesis. Genetics, 141(1), 191-202. PMID: 8536967.

Scott, K. S., Geyer, P. K. (1995). Effects of the su(Hw) insulator protein on the expression of the divergently transcribed Drosophila yolk protein genes. The EMBO journal, 14(24), 6258-67. PMID: 8557045.

Roseman, R. R., Johnson, E. A., Rodesch, C. K., Bjerke, M., Nagoshi, R. N. & Geyer, P. K. (1995). A P element containing suppressor of hairy-wing binding regions has novel properties for mutagenesis in Drosophila melanogaster. Genetics, 141(3), 1061-74. PMID: 8582613.

Roseman, R. R., Swan, J. M. & Geyer, P. K. (1995). A Drosophila insulator protein facilitates dosage compensation of the X chromosome min-white gene located at autosomal insertion sites. Development (Cambridge, England), 121(11), 3573-82. PMID: 8582271.

Bae, E., Cook, K. R., Geyer, P. K. & Nagoshi, R. N. (1994). Molecular characterization of ovarian tumors in Drosophila. Mechanisms of development, 47(2), 151-64. PMID: 7811638.

Geyer, P. K., Patton, J. S., Rodesch, C. & Nagoshi, R. N. (1993). Genetic and molecular characterization of P element-induced mutations reveals that the Drosophila ovarian tumor gene has maternal activity and a variable null phenotype. Genetics, 133(2), 265-78. PMID: 8436275.

Roseman, R. R., Pirrotta, V. & Geyer, P. K. (1993). The su(Hw) protein insulates expression of the Drosophila melanogaster white gene from chromosomal position-effects. The EMBO journal, 12(2), 435-42. PMID: 8382607.

Geyer, P. K., Corces, V. G. (1992). DNA position-specific repression of transcription by a Drosophila zinc finger protein. Genes & development, 6(10), 1865-73. PMID: 1327958.

Patton, J. S., Gomes, X. V. & Geyer, P. K. (1992). Position-independent germline transformation in Drosophila using a cuticle pigmentation gene as a selectable marker. Nucleic acids research, 20(21), 5859-60. PMID: 1333590.

Corces, V. G., Geyer, P. K. (1991). Interactions of retrotransposons with the host genome: the case of the gypsy element of Drosophila. Trends in genetics : TIG, 7(3), 86-90. PMID: 1851585.

Geyer, P. K., Chien, A. J., Corces, V. G. & Green, M. M. (1991). Mutations in the su(s) gene affect RNA processing in Drosophila melanogaster. Proceedings of the National Academy of Sciences of the United States of America, 88(16), 7116-20. PMID: 1714588.

Geyer, P. K., Green, M. M. & Corces, V. G. (1990). Tissue-specific transcriptional enhancers may act in trans on the gene located in the homologous chromosome: the molecular basis of transvection in Drosophila. The EMBO journal, 9(7), 2247-56. PMID: 2162766.

Harrison, D. A., Geyer, P. K., Spana, C. & Corces, V. G. (1989). The gypsy retrotransposon of Drosophila melanogaster: mechanisms of mutagenesis and interaction with the suppressor of Hairy-wing locus. Developmental genetics, 10(3), 239-48. PMID: 2472241.

Geyer, P. K., Green, M. M. & Corces, V. G. (1988). Induction of Mutant Phenotypes by a Drosophila melanogaster Retrotransposon Requires Sequences Homologous to Mammalian Enhancers. Proceedings of the National Academy of Sciences, 85, 8593-8597.

Geyer, P. K., Green, M. M. & Corces, V. G. (1988). Mutant gene phenotypes mediated by a Drosophila melanogaster retrotransposon require sequences homologous to mammalian enhancers. Proceedings of the National Academy of Sciences of the United States of America, 85(22), 8593-7. PMID: 2847167.

Geyer, P. K., Green, M. M. & Corces, V. G. (1988). Reversion of a gypsy-induced mutation at the yellow (y) locus of Drosophila melanogaster is associated with the insertion of a newly defined transposable element. Proceedings of the National Academy of Sciences of the United States of America, 85(11), 3938-42. PMID: 2836866.

Geyer, P. K., Richardson, K. L., Corces, V. G. & Green, M. M. (1988). Genetic instability in Drosophila melanogaster: P-element mutagenesis by gene conversion. Proceedings of the National Academy of Sciences of the United States of America, 85(17), 6455-9. PMID: 2842772.

Geyer, P. K., Corces, V. G. (1987). Separate regulatory elements are responsible for the complex pattern of tissue-specific and developmental transcription of the yellow locus in Drosophila melanogaster. Genes & development, 1(9), 996-1004. PMID: 3123324.

Geyer, P. K., Green, M. M. & Corces, V. G. (1987). Molecular basis of transposable element-induced mutations in Drosophila melanogaster., e. M. Lambert & J. F. McDonald , I. B. Weinstein (Eds.) Eukaryotic Transposable Elements as Mutagenic Agents: CSHLP, Cold Spring Harbor, N.Y.

Geyer, P. K., Spana, C. & Corces, V. G. (1986). On the molecular mechanism of gypsy-induced mutations at the yellow locus of Drosophila melanogaster. The EMBO journal, 5(10), 2657-62. PMID: 3096713.

Geyer, P. K., Fyrberg, E. A. (1986). 5'-flanking sequence required for regulated expression of a muscle-specific Drosophila melanogaster actin gene. Molecular and cellular biology, 6(10), 3388-96. PMID: 3025590.

Jenh, C. H., Geyer, P. K., Baskin, F. & Johnson, L. F. (1985). Thymidylate synthase gene amplification in fluorodeoxyuridine-resistant mouse cell lines. Molecular pharmacology, 28(1), 80-5. PMID: 2991733.

Jenh, C. H., Geyer, P. K. & Johnson, L. F. (1985). Control of thymidylate synthase mRNA content and gene transcription in an overproducing mouse cell line. Molecular and cellular biology, 5(10), 2527-32. PMID: 3837178.

Geyer, P. K., Johnson, L. F. (1984). Molecular cloning of DNA sequences complementary to mouse thymidylate synthase messenger RNA. The Journal of biological chemistry, 259(11), 7206-11. PMID: 6144683.

Geyer, P. K., Meyuhas, O., Perry, R. P. & Johnson, L. F. (1982). Regulation of ribosomal protein mRNA content and translation in growth-stimulated mouse fibroblasts. Molecular and cellular biology, 2(6), 685-93. PMID: 14582163.