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Michelle Starz-Gaiano, Ph.D.

Associate Professor

Michelle Starz-Gaiano

Office: BS 212
Phone: 410-455-2217
Lab: BS 206/208/216
Lab Phone: 410-455-2486
Email: starz@umbc.edu

Research Group

 

Education

Postdoctoral, Johns Hopkins School of Medicine, 2008
PhD, New York University, 2002
BS, Massachusetts Institute of Technology, 1994

Professional Interests

Border cells move out of the epithelium

Border cells move out of the epithelium

Research interests: cell migration

In many instances, cells must migrate long distances to fulfill their destiny. For example, numerous cell types in developing embryos are born some distance away from where they will be required in the fully formed organism. In the case of an injury, immune cells travel to the site to fight infections, and skin cells move to repair a wound. These migrations occur with great precision in time and space such that few cells get lost. As someone who needs an alarm clock to wake up and a map to get around Baltimore, I think this is amazing. How are cells selected to become motile cells, and detach from their neighbors that stay behind? How do they know when it is time to go? What signals guide their movements through complex tissues? How do they “put on the brakes” when it is time to stop? These questions are of fundamental interest to developmental biologists, and have major implications in medicine as well. Defects in cell migration can lead to birth defects in humans. In addition, cancers are most lethal when they become metastatic, acquiring the ability to leave a tumor and spread and hide throughout the body.

I am currently using Drosophila melanogaster as a model system for addressing unanswered questions in cell movement. The vast array of genetic tools in fruit flies, as well as their fast generation time and small size, makes them ideal for these studies. Also, it has been shown that genes involved in cell movements in flies also play roles in cell migration and cancer metastasis in vertebrates (reviewed in Jang et al 2007; Naora and Montell, 2005).

Specifying a migratory cell population

Wild type and mutant egg chambers

Wild type and mutant egg chambers

The current focus of the lab is on the movement of the border cells, a cluster of cells in the ovary that detach from an epithelial cell layer and undergo a stereotyped movement between germ line cells as the egg develops (schematized in Figure 1). Border cells ultimately form a structure that allows the egg to be fertilized. We have found a three-component genetic circuit of transcription factors that is responsible for specifying the correct number of motile cells. Loss or overexpression of any of the genes –apontic, stat, or slow border cells – causes too many cells to become motile, and thereby disrupts cell migration (see Figure 2 for an example of an apontic (apt) loss of function phenotype). We are interested in the downstream mechanisms responsible for this defect; in particular, what molecules cause the cells to remain attached to their neighbors when they should disconnect? Regulation of cell adhesion molecules such as Cadherins are likely to be involved in this detachment step, and this is being investigated. apontic and stat are also required for morphogenesis of tube formation of the tracheal system during fly embryogenesis, and we are interested in further characterizing their interactions and functions during this migratory process.

Steroid hormone control of timing

Border cells are specified significantly before they begin to migrate. As is the case for humans, steroid hormones in insects are responsible for coordinating developmental events over time, and it has been shown that a steroid hormone signal gives the border cells a cue to go now. There is only one steroid hormone in flies, called ecdysone. Like other hormones, ecdysone binds to a receptor, which translocates to the nucleus to initiate a cascade of transcription. Ecdysone receptor acts in a complex with several required co-factors including Ultraspiracle, the fly homolog to human RXR, and Taiman, which shares homology with the breast cancer oncogene amplified in breast cancer 1 (AIB1/SRC-3). All of these genes are required for border cell migration (Bai, 2000). We are very interested in the downstream signals that instruct border cells to “go” and have completed microarray experiments to identify target genes. Loss of function and gain of function studies are underway to identify critical targets and to determine which genes are required for cell migration. Required genes may likely play a role in breast and ovarian cancer metastases.

References:

1 Jang AC, Starz-Gaiano M, Montell DJ. Modeling migration and metastasis in Drosophila. J Mammary Gland Biol Neoplasia. 2007 Sep;12(2-3):103-14.

2 Naora H, Montell DJ. Ovarian cancer metastasis: integrating insights from disparate model organisms. Nat Rev Cancer. 2005 May;5(5):355-66.

3 Bai J, Uehara Y, Montell DJ. Regulation of invasive cell behavior by taiman, a Drosophila protein related to AIB1, a steroid receptor coactivator amplified in breast cancer. Cell. 2000 Dec 22;103(7):1047-58.

Publications

Monahan, AJ, and Starz-Gaiano, M.  SOCS36E Attenuates STAT Signaling to Limit Cell Motility in the Drosophila Ovary. Developmental Biology 2013, July 15, 379; 152-166.
[Abstract]

Montell, DJ, Yoon, WH, Starz-Gaiano, M. Group Choreography: Molecular Mechanisms Orchestrating the Collective Movement of Border Cells. Nature Reviews Molecular Cell Biology 2012, Oct;13(10): 631-45.
[Abstract]

Cho I, Horn, L, Felix, TM, Foster, L, Gregory, G, Starz-Gaiano, M, Chambers, M, De Luca M, Leips J.  Age- and diet- specific effects of variation at S6 kinase on life history, metabolic and immune response traits in Drosophila melanogaster. DNA and Cell Biology, 2010, Sept; 29(9):473-85.
[Abstract]

Starz-Gaiano M, Melani M, Meinhardt H, Montell D. Interpretation of the UPD/JAK/STAT morphogen gradient in Drosophila follicle cells. Cell Cycle 2009 Sep 15;8(18):2917-25.
[Abstract]

Renault AD, Ricardo S, Kunwar PS, Santos A, Starz-Gaiano M, Stein JA, Lehmann R. Hedgehog does not guide migrating Drosophila germ cells. Dev Biol. 2009 Apr 15;328(2):355-62
[Abstract] [Text]

Starz-Gaiano M, Melani M, Wang X, Meinhardt H, Montell DJ. Feedback inhibition of Jak/STAT signaling by apontic is required to limit an invasive cell population. Developmental Cell. 2008 May;14(5):726-38.
[Abstract]

Prasad M, Jang AC, Starz-Gaiano M, Melani M, Montell DJ. A protocol for culturing Drosophila melanogaster stage 9 egg chambers for live imaging. Nature Protocols 2007;2(10):2467-73.
[Abstract]

Jang AC, Starz-Gaiano M, Montell DJ. Modeling migration and metastasis in Drosophila. J Mammary Gland Biol Neoplasia. 2007 Sep;12(2-3):103-14. Review.
[Abstract]

Starz-Gaiano M, Montell DJ. Genes that drive invasion and migration in Drosophila. Curr Opin Genet Dev. 2004 Feb;14(1):86-91. Review.
[Abstract]

Kunwar PS, Starz-Gaiano M, Bainton RJ, Heberlein U, Lehmann R. Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells. PLoS Biol. 2003 Dec;1(3):E80.
[Abstract]

Renault AD, Starz-Gaiano M, Lehmann R. Metabolism of sphingosine 1-phosphate and lysophosphatidic acid: a genome wide analysis of gene expression in Drosophila. Mech Dev. 2002 Dec;119 Suppl 1:S293-301.
[Abstract]

Starz-Gaiano M, Lehmann R. Moving towards the next generation. Mech Dev. 2001 Jul;105(1-2):5-18. Review.
[Abstract]

Starz-Gaiano M, Cho NK, Forbes A, Lehmann R. Spatially restricted activity of a Drosophila lipid phosphatase guides migrating germ cells. Development. 2001 Mar;128(6):983-91.
[Abstract]

Verona R, Moberg K, Estes S, Starz M, Vernon JP, Lees JA. E2F activity is regulated by cell cycle-dependent changes in subcellular localization. Mol Cell Biol. 1997 Dec;17(12):7268-82.
[Abstract]

Moberg K, Starz MA, Lees JA. E2F-4 switches from p130 to p107 and pRB in response to cell cycle reentry. Mol Cell Biol. 1996 Apr;16(4):1436-49.
[Abstract]

Courses Taught

BIOL 303: Cell Biology
BIOL 443: Advanced Topics in Developmental Biology
BIOL 420:  Advanced Topics in Cell Biology
BIOL 750:  Advanced Topics in Organismic Biology (Developmental Genetics)