Vicki Losick

Education

  • B.S., Bates College
  • Ph.D.,Tufts Medical School
  • Postdoc with Allan Spradling at Carnegie Institution

Research Interests

Scientists have been working with the fruit fly, Drosophila melanogaster, for more than 100 years to answer fundamental questions in biology. The Losick Lab takes advantage of the ease and power of Drosophila genetics to understand the basic mechanisms of tissue repair.

Wound healing is not a one-size-fits-all process. While the typical wound healing response relies on cell division to regenerate the cells that are lost by injury, aging, or disease. We found that cells can also be replaced by stimulating existing cells to grow in size by becoming polyploid, a process named wound-induced polyploidization (WIP).  A polyploid cell is a cell that has more than diploid copy of its chromosomes.  As a result, polyploid cells can grow to be many orders of magnitude larger than their diploid cell counterparts.  Polyploid cells are ubiquitous in insects and plants, but also are also required for the development of many tissues in our body.  What remains unknown is why under conditions of stress, like injury, aging, and disease, polyploid cells frequently arise?  and how do polyploid cells function during these stress responses?

We are beginning to answer these fundamental questions using the fruit fly as a model.  Fruit fly puncture wounds (Figure 1) heal by WIP where cells grow in size forming both mono and multi-nucleated enlarged cells (Figure 2).  We found that cell enlargement through polyploidization is required for wound healing, since wounds fail to close if WIP is genetically perturbed in Drosophila.  In collaborative work, we recently discovered that WIP also functions in mammals to maintain the size and functional capacity of the repaired tissue by enlarging existing cells in mouse cornea endothelium. Therefore, WIP appears to be a conserved and widely used part of the body’s healing arsenal.  The Losick laboratory is currently studying the molecular mechanisms regulating WIP in flies and mice in order to understand how to generate these extra-large cells to improve our bodies ability to heal.

Selected Publications

  • Losick, VP, Jun, AS, and Spradling, AC. Wound-Induced Polyploidization: Regulation by Hippo and JNK Signaling and Conservation in Mammals. PLoS One. 2016 Mar 9;11(3):e0151251.
  • Losick VP. Wound-induced polyploidy is required for tissue repair. Adv Wound Care. 2014, ahead of print. doi:10.1089/wound.2014.0545. Review.
  • Losick, VP, Fox DT, and Spradling, AC. Polyploidization and cell fusion contribute to wound healing in the adult Drosophila epithelium. Current Biology. 2013, Nov 18; 23(22):2224-32.
  • Liu M, Uehara T, Losick VP, Park JT, and Isberg RR. A Legionella pneumophila protein that facilitates evasion from Nod1 recognition. Cell Host Microbe. 2012, Aug 16; 12(2):166-76.
  • Losick VP, Morris LX, Fox DT, Spradling A. Drosophila stem cell niches: a decade of discovery suggest a unified view of stem cell regulation. Developmental Cell. 2011, Jul 19; 21(1):159-71. Review.
  • Losick VP, Haenssler E, Moy M, and Isberg RR. LnaB: a Legionella pneumophila activator of NF-kappaB. Cell Microbiology. 2010, Aug; 12(8):1083-97.
  • Li Z, Dugan AS, Bloomfield G, Skelton J, Ivens A, Losick VP, and Isberg RR. The amoebal MAP kinase response to Legionella pneumophila is regulated by DupA. Cell Host Microbe. 2009, Sep 17; 6(3):253-67.
  • Losick VP*, Stephan KS*, Isberg, RR, Poltorak A. A hemidominant Naip5 allele in MOLF/Ei-derived macrophages restricts L. pneumophila intracellular growth. Infection and Immunity. 2009, Jan; 77(1):196-204. *Co-primary authors.
  • Losick VP and Isberg RR. NF-appaB translocation prevents host cell death after low-dose challenge by Legionella pneumophila. Journal of Experimental Medicine. 2006, Sep 4; 203(9):2177-89.
  • Losick VP, Schlax PE, Emmons RA, Lawson TG. Signals in Hepatitis A Virus P3 region proteins recognized by the ubiquitin-mediated proteolytic system. Virology. 2003, May 10; 309(2):306-19.

Grants

  • 2015 — The Molecular Mechanisms Regulating Wound-Induced Polyploidy from COBRE National Institutes of Health NIGMS

Dissertation Students:

https://gsbse.umaine.edu/people/kayla-gjelsvik/