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Laura  Johnston
Laura Johnston
Associate Professor of Genetics and Development


Address: 701 West 168th Street Room 704 New York NY 10032
Phone: 212-305-1688
Fax: 212-305-1752
E-mail:

lj180@columbia.edu

Education and Training:
Ph.D. 1994, University of Washington
Postdoctoral Fellow 1994-1996, University of Washington
Postdoctoral Fellow 1996-2000, Fred Hutchinson Cancer Research Center
Affiliations:
bullet  Department of Genetics and Development
bullet  Herbert Irving Comprehensive Cancer Research Center
Training Activities:
bullet  Department of Genetics and Development
bullet  Department of Biological Sciences
bullet  Integrated Program in Molecular, Cellular and Biophysical Studies
Research Summary:
(800 words, max)
Growth control during organ development: linkage between pattern formation and growth
Current Research:
Our research goal is to understand how developing organs grow and cease growth - and to define the relationship between pattern specification and growth regulation. We use the simple genetic model organism Drosophila, and utilize strategies that allow manipulation of growth in living, growing animals. Our studies attempt to define the organ-intrinsic growth regulatory program in molecular terms.

Our working hypothesis is that the growth regulator, dMyc, is at the heart of this genetic program. In the developing wing dMyc receives regulatory input from patterning morphogens such as Wingless and Dpp. We postulate that this information is used in two ways: First, it promotes or constrains growth in a region-specific manner, enhancing shape formation; and second, the information is translated into a comparison of dMyc levels between individual cells, allowing the cells to sense and respond to growth changes in their immediate environment through a process called cell competition. Recent work from the lab indicates that cell competition also involves cooperative interactions between neighboring cells, ensuring optimal organ fitness.

The cellular plasticity inherent in many growing organs is important for normal growth and critical for regeneration to occur. We use tissue regeneration as a model system for studying plasticity during growth. Our studies of regeneration and compensatory proliferation have demonstrated a novel - and probably atavistic - role for Drosophila p53 in coordinating the growth, cell cycle and fate alterations required during tissue regeneration.

We are also investigating how developmental timing affects growth (and vice versa). let-7 is a highly conserved, temporally regulated, non-coding microRNA (miR) that is required in the nematode, C. elegans, to regulate the cell cycle exit of a specific group of larval cells and the timing of the L4-adult developmental transition. To investigate the role of let-7 in control of developmental timing in Drosophila, we have generated a let-7 mutant. We find that Drosophila let-7 mutants undergo excess cell divisions in the pupal wing, indicating that it functions as a heterochronic regulator to limit cell division during metamorphosis. let-7 mutants also display numerous behavioral defects suggesting abnormalities in neuromuscular function.

Publications:
(6 max)
1. Johnston, L.A: (2009) Competitive interactions between cells: Death, growth and geography.  Science  324: 1679-1682

2. Neto-Silva, R. M., Wells, B. S. and Johnston, L. A : (2009) Mechanisms of growth and homeostasis in the Drosophila wing.  Annual Reviews of Cell and Developmental Biology  25: 

3. Caygill, E.E. and Johnston, L. A : (2008) Temporal regulation of metamorphic processes in Drosophila by the let-7 and miR-125 heterochronic microRNAs.  Current Biology  18: 943-950

4. Senoo-Matsuda, N. and Johnston, L. A: (2007) Soluble factors mediate competitive and cooperative interactions between cells expressing different levels of Drosophila Myc.  Proc. Nat. Acad.Sci  104(47): 18543-18548

5. Wells, B.S., Yoshida, E., and Johnston, L. A: (2006) Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity.  Current Biology  16(16): 1-10

6. de la Cova, C., Abril, M., Bellosta, P., Gallant, P., and Johnston, L. A: (2004) Drosophila Myc regulates organ size by inducing cell competition.  Cell  117: 107-116

URL for lab page:
 

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