Associate Professor of Biology
B.A., Grinnell College;
Ph.D., University of Iowa
Member of: Institute of Molecular Biology
Office: Streisinger Hall Room 312
Telephone: 541-346-5183
Lab: Streisinger Hall Room 315
Telephone: 541-346-5994
Email
Research Interests
We are interested in how an organism adapts to the physiological challenges of daily life and what this tells us about the physiological and developmental responses to disease in humans. The particular challenge we study is the response to low oxygen. When faced with inadequate oxygen (hypoxia), animals undergo a series of transient and longer-term changes to increase their access to oxygen and decrease their need for it. If oxygen homeostasis is not restored, death or serious tissue damage can result. In humans, serious pathology can also result when the hypoxic responses are inappropriately activated, as in rapidly proliferating tumors that turn on hypoxia-response programs that promote tumor angiogenesis and growth.
How does a cell sense oxygen?
We are studying the sensing and response to low oxygen in Drosophila melanogaster. The key regulator of the hypoxic response is shared between the fly and humans, and we are taking genetic approaches to dissect the molecular pathways that allow a cell to measure oxygen need and quickly respond when the oxygen supply is limiting.
Airway branches (arrows) proliferate on a hypoxic muscle (bracket). Cells experiencing oxygen debt activate a fluorescent reporter gene which can be observed in living animals.
How does an organism respond to low oxygen?
The genetics of Drosophila is complemented by the ability to take genomic approaches as well. We have been part of initiating the use of microarray technology, in which the transcriptional activity of every gene in the genome is measured simultaneously, and have used it to assay the rapid and complex changes in response to low oxygen. Other stresses evoke similar patterns of gene expression, so computational approaches are employed to find highly significant response genes and understand the biology of these changes.
A Drosophila microarray reflecting the transcriptional activity of over 6000 genes. Each dot represents a single gene, and the color indicates the amount of that transcript in hypoxic animals.
Cell and developmental biology of the response
Although many responses to low oxygen are at the cellular level, we are also studying longer-term developmental changes. One mechanism for adaptation is the outgrowth of airway branches to hypoxic regions by a fibroblast growth factor signaling pathway. We have also identified a novel cellular response to hypoxia--the formation of long epidermal projections that grow out to nearby airway branches. The signals that control this behavior are unknown.
Hypoxic epidermal cells form filopodia (arrow) that reach out to nearby tracheal cells.
Many developmental pathways have been extensively studied in Drosophila. Physiological pathways, which are just as crucial for survival of an organism, are still poorly understood. We use the traditional strength of Drosophila (genetic screens) combined with emerging strengths (cell biology and genomics) to learn more about the biologically interesting and medically important question of oxygen sensing and response.
Selected Publications
Baird NA, Etter PD, Atwood TS, Currey MC, Shiver AL, Lewis ZA, Selker EU,Cresko WA, Johnson EA. Rapid SNP discovery and genetic mapping using sequenced RAD markers. PLoS ONE. 2008;3(10):e3376. Epub 2008 Oct 13.
Lewis ZA, Shiver AL, Stiffler N, Miller MR, Johnson EA, Selker EU. High-density detection of restriction-site-associated DNA markers for rapidmapping of mutated loci in Neurospora. Genetics. 2007 Oct;177(2):1163-71. Epub 2007 Jul 29.
Miller MR, Atwood TS, Eames BF, Eberhart JK, Yan YL, Postlethwait JH, Johnson EA. RAD marker microarrays enable rapid mapping of zebrafish mutations. Genome Biol. 2007;8(6):R105.
Miller MR, Dunham JP, Amores A, Cresko WA, Johnson EA. Rapid and cost-effective polymorphism identification and genotyping using restriction site associated DNA (RAD) markers. Genome Res. 2007 Feb;17(2):240-8.
Baird NA, Turnbull DW, Johnson EA. Induction of the heat shock pathway during hypoxia requires regulation of heatshock factor by hypoxia-inducible factor-1. J Biol Chem. 2006 Dec 15;281(50):38675-81.
Liu G, Roy J, Johnson EA. Identification and function of hypoxia-response genes in Drosophila melanogaster. Physiol Genomics. 2006 Mar 13;25(1):134-41.
Johnson, E., Estes, P., Crews, S., and Krasnow, M.A.. Conservation and function of the HIF-1 hypoxia response pathway in living Drosophila. Manuscript in preparation.
Hollich V, Johnson E, Furlong E, Beckmann B, Carlson J., Celniker S, Hoheisel J. (2004) Arraying the Drosophila genome; provision of a resource. Biotechniques, 2004 Aug;37(2):282-4.
Freeman MR, Delrow J, Kim J, Johnson E, Doe CQ. (2003) Unwrapping glial biology: Gcm target genes regulating glial development, diversification, and function. Neuron. 2003 May 22;38(4):567-80.
Cho N.K., L. Keyes, E. Johnson, J. Heller, L. Ryner, F. Karim, and M.A. Krasnow. (2002) Developmental control of blood cell migration by the Drosophila VEGF pathway. Cell 108:865-76.
Arbeitman, M., E. Furlong, F. Imam, E. Johnson, B. Null, B. Baker, M.A. Krasnow, M. Scott, R. Davis, and K. White. (2002) Gene Expression During the Life Cycle of Drosophila melanogaster. Science 297: 2270-5.
Johnson, E., J. Jarecki, and M.A. Krasnow. (1999) Oxygen regulation of airway branching in Drosophila is mediated by Branchless FGF. Cell 99:211-20.
297 Klamath Hall Hall