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Michael J. Galko

Michael Galko

E-mail: mjgalko@mdanderson.org

Assistant Professor, The University of Texas, M.D. Anderson Cancer Center

B.S., University of Texas at Austin, 1991
Ph.D., University of California at San Francisco, 1999
Postdoc, Stanford University School of Medicine, Stanford, CA, 2000-05

Molecular genetics of tissue repair responses in Drosophila

Multicellular organisms have evolved a variety of tissue repair responses to cope with tissue damage. Some of these responses (wound closure) are aimed at restoring structure and function to the damaged tissue(s) while others (inflammation and nociceptive sensitization) are aimed at protecting the organism from further infection or injury. My laboratory is interested in identifying the elusive signals that initiate and terminate different aspects of the organismal tissue repair response, as well as the genes that are required to execute each specific response. Ultimately, we wish to understand in molecular detail how the activities of diverse damage-responsive cell types are coordinated in space and time to give a functional tissue repair program. To pursue these interests we have developed a variety of tissue repair/response assays in the highly genetically tractable model organism, Drosophila melanogaster and are focusing our efforts on three critical responses: epidermal wound closure, inflammation (recruitment of blood cells to the site of injury), and nociceptive sensitization (lowering of the threshold for sensing painful stimuli following injury). Given that tissue repair responses are an ancient survival mechanism of multicellular animals, we expect that the functional importance of many of these genes we identify will be conserved between flies and vertebrates. Below is a summary of some of the projects ongoing in the lab.

  • Cellular and genetic analysis of epidermal wound closure: To study epidermal healing we developed wound healing assays using Drosophila larvae (PloS Biology, 2004) and showed that epidermal repair proceeds by a similar sequence of steps and involves functionally equivalent cell types to those in vertebrates. Some of the hallmarks of the Drosophila repair process include recruitment of blood cells, epidermal cell orientation and fusion, epidermal activation of the Jun N-terminal kinase (JNK) signaling pathway, JNK-dependent reepithelialization of the wound site, and clearance of cell debris and scab material. Recently, we developed transgenic larvae that allow live visualization of epidermal wound responses and enable the performance of large-scale genetic screens designed to identify the complement of Drosophila genes that are required for various steps of epidermal healing. These screens are ongoing.

  • Establishment of a genetically tractable model of tissue damage-induced nociceptive sensitization: Local alterations in nociception (pain sensation) are a hallmark of tissue damage in vertebrate organisms. Nociceptive sensitization can involve a lowering of the pain threshold such that previously non-noxious stimuli are perceived as painful (allodynia), as well as a faster or exaggerated response to supra-threshold stimuli (hyperalgesia). Sensitization serves to foster behaviors that protect sites of tissue damage while they heal. We have shown that both hyperalgesia and allodynia develop following UV irradiation in Drosophila larvae and that allodynia depends on a conserved tumor necrosis factor (TNF)-like cytokine that is produced by the irradiated epidermal cells and on a TNF receptor-like protein present on nociceptive sensory neurons (Current Biology, 2009). We are currently using genetic and cell biological approaches to define the molecular consequences of activating the TNF-receptor in sensory neurons so that we can understand how tissue damage leads to adaptive alterations in the behavioral response threshold of nociceptive sensory neurons.

Selected Publications

Galko MJ, Tessier-Lavigne M (2000) Function of an axonal chemoattractant modulated by metalloprotease activity. Science 289:1365-1367.

Galko MJ, Tessier-Lavigne M (2000) Biochemical characterization of netrin-synergizing activity. Journal of Biological Chemistry 275:7832-7838.

Galko MJ, Krasnow MA (2004) Cellular and genetic analysis of wound healing in Drosophila larvae. PLoS Biology 2:E239.

Babcock DT, Brock AR, Fish GS, Wang Y, Perrin L, Krasnow MA, Galko MJ (2008) Circulating blood cells function as a surveillance system for damaged tissue in Drosophila larvae. Proceedings of the National Academy of Sciences USA 105:10017-10022.

Wu Y, Brock AR, Wang Y, Fujitani K, Ueda R, Galko MJ (2009) A blood-borne PDGF/VEGF-like ligand initiates wound-induced epidermal cell migration in Drosophila larvae. Current Biology 19:1473-1477.

Babcock DT, Galko MJ (2009) Two sides of the same coin no longer: genetic separation of nociceptive sensitization responses. Communicative and Integrative Biology 2:517-519.

Babcock DT, Landry C, Galko MJ (2009) Cytokine signaling mediates UV-induced nociceptive sensitization in Drosophila larvae. Current Biology 19:799-806.

Lesch C, Jo J, Wu Y, Fish GS, Galko MJ (2010) A targeted UAS-RNAi screen in Drosophila larvae identifies wound closure genes regulating distinct cellular processes. Genetics 186:943-957.

Babcock DT, Shi S, Jo J, Shaw M, Gutstein HB, Galko MJ (2011) Hedgehog signaling regulates nociceptive sensitization. Current Biology 21:1525-1533.

Brock AR, Wang Y, Berger S, Renkawitz-Pohl R, Han VC, Wu Y, Galko MJ (2012) Transcriptional regulation of Profilin during wound closure in Drosophila larvae. Journal of Cell Science, in press.

Contact Information

Michael J. Galko, Ph.D.
Department of Biochemistry and Molecular Biology, Unit 1000
The University of Texas M.D. Anderson Cancer Center
1515 Holcombe Blvd. S11.8336A
Houston, Texas 77030, U.S.A.

Tel: (713) 792-9182
Fax: (713) 834-6291
E-mail: mjgalko@mdanderson.org

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