Dr. Deni S. Galileo

Associate Professor

Contact

Galileo

Office: 232 Wolf Hall
Lab: 248 Wolf Hall

Mailing address:
Department of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716

Phone: (302) 831-1277
Fax: (302) 831-2767
E-mail: dgalileo@udel.edu

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Education

B.A.: New College of Florida
Ph.D.: University of Florida College of Medicine and Whitney Laboratory
Postdoctoral: Washington University School of Medicine

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Research Interests

The focus of my laboratory has been the study of migrating cells, both normal and abnormal, in the developing brain. This endeavor has utilized the chick embryo as the model system and recombinant retroviral vectors as a main tool to express or attenuate specific proteins. Investigating mechanisms of normal neuronal migration in the developing brain using retroviral vectors has led to related studies of programmed cell death, oligodendrocyte development, gene therapy, and the effects of the viral oncogene v-src. v-src's transforming effects on migrating neurons have since been extended to the study of a particularly lethal form of abnormally migrating cell in the brain: gliomas. In my laboratory we have uncovered basic mechanisms of normal vertebrate brain development, explored and established new in vivo models of human disease, and developed new in vitro technology that has been employed for the study of both.

Using the developing chick optic tectum (midbrain) as the model for vertebrate brain development, a variety of methods are used to investigate these processes. A main technology we use for this is one that I helped to develop: retroviral gene transfer. Here, a recombinant retroviral vector carrying a marker gene and another cDNA (or its antisense copy) can be used in vivo to infect brain progenitor cells that line the ventricular cavity. The retroviral vector will incorporate the recombinant DNA into the infected cell's genome and express it. Then, we can analyze how the expressed single protein (or the antisense-attenuated endogenous protein) affects the processes we are interested in. For example, we were the first to show that integrin extracellular matrix receptors were involved in brain development by using retroviral transduction in vivo of antisense sequences against β1 integrins. This caused infected neuroblasts to fail to migrate into superficial brain laminae, and then, to die. Similar experiments followed to show specifically that integrin heterodimers α6β1 and α8β1 were responsible for correct cell migration and survival, respectively. Replication-incompetent retroviral vectors are used when cell-autonomous effects are desired, and now we are using replication-competent vectors and in ovo electroporation to achieve widespread misexpression of several proteins in developing brain.We are investigating the roles of suspected integrin extracellular matrix substrates in migration and survival. We are also investigating the roles during brain development of other adhesion molecules (e.g. L1/NgCAM), contactin, the proto-oncogene c-src, and its viral counterpart oncogene v-src.

A focal point of the lab now is to further develop and utilize the chick embryo as a model for the study and manipulation of basic mechanisms of abnormal brain cell migration- i.e. glioma tumor cell local invasiveness and breast cancer spread to brain. This is a logical extension of our v-src, integrin, and NgCAM/L1 work, and is of interest because the insidious nature of glioma cells lies in their capacity to extensively migrate throughout the brain, particularly along axon tracts and blood vessels. This extensive migration usually precludes successful resection of the tumor by surgery. I believe that some of the same molecules and mechanisms that are used during normal neuronal migration are usurped by glioma and other cancer cell types that spread in the brain. These tumor cells are also more amenable to culture and in vitro assays than are normal brain cells, which allows meticulous dissection of postulated migratory mechanisms under a variety of in vitro conditions. Toward this new focus, we have shown that human and rat glioma tumor cell lines are capable of producing invasive tumors in the developing chick brain and are now beginning such experiments to determine whether primary human glioma tumor cells from surgical samples do this as well. This novel chick model ultimately should be as useful as immunodeficient mice for studying certain mechanisms of invasive brain tumors, and it has several practical advantages like accessibility, ease of manipulation, and cost. We also have shown that human breast cancer cells injected into the extraembryonic blood vessels of the chick embryo extravasate and invade the brain within days. Brain metastases from breast cancer often kill within weeks to months, and this new model undoubtedly will prove useful in studying certain aspects of metastasis, like homing to brain and extravasation. In collaboration with Dr. John Koh (UD Dept. of Chemistry and Biochemistry) we also have begun a project determining the effects on axon outgrowth of patterns of gene expression in cell monolayers that are induced by light.

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Current Projects

• Control of invasiveness of glioma tumor cells within brain.
• Control of metastasis of breast cancer cells to brain and other organs.
• Roles of integrins and extracellular matrix molecules in neuronal migration and survival in developing brain.
• Axon outgrowth on cells with patterned gene expression.

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Teaching

• BISC 305* - Cell Physiology
• BISC 439/639* - Developmental Neurobiology

*Course web site available through MyCourses

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Research Group

• Yupei Li, M.S. - Graduate Student (M.S., Nanjing University, China). Autocrine stimulation of breast cancer cell motility.
• Kalyani Chilukuri, B.Tech. - Graduate Student (B.Tech., Indian Institute of Technology Madras, India). Autocrine stimulation of cell motility in human breast cancer cell lines.
• Grace Yang, B.S. - Graduate Student (B.S., Peking University Health Science Center, China). Glioma tumor cell invasiveness.
• Katy Teixeira - Junior, Metastasis of breast cancer cell lines to brain.
• Cory Bovenzi - Sophomore, Neuronal migration and survival in developing brain.
• Mike Fascelli - Sophomore, Adult brain progenitor cells.

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Selected Publications

Farach, A.M. and D.S. Galileo (2009). O-GlcNAc modification of radial glial vimentin filaments in the developing chick brain. Brain Cell Biology, Jan 9 [Epub ahead of print].

Griffiths, G.S., K.A. Miller, D.S. Galileo, P.A. Martin-DeLeon (2007). SPAM1 is secreted by the estrous murine uterus and oviduct in a form which can bind to sperm during capacitation: Acquisition enhances hyaluronic acid-binding ability and cumulus penetration efficiency. Reproduction, 135, 1-10.

Tian, J., C. Paquette-Straub, E.H. Sage, S.E. Funk, V. Patel, D.S. Galileo, and M.A. McLane (2007). Inhibition of melanoma cell motility by the snake venom disintegrin eristostatin. Toxicon, 50(3), 448.

Fotos, J.S., V.P. Patel, N.J. Karin, M.K. Temburni, J.T. Koh, and D.S. Galileo (2006). Automated time-lapse microscopy and high-resolution tracking of cell migration. Cytotechnology, 51(1), 7-19.

Masiello, L.M., J.S. Fotos, D.S. Galileo, and N.J. Karin (2006). Lysophosphatidic acid induces chemotaxis in MC3T3-E1 osteoblastic cells. Bone, 39(1), 72-82.

Chen, H., G. Griffiths, D.S. Galileo, and P.A. Martin-Deleon (2006). Epididymal SPAM1 is a marker for sperm maturation in the mouse. Biol. Reprod., 74(5), 923-930.

Cretu, A., J.S. Fotos, B.W. Little, and D.S. Galileo (2005). Human and rat glioma growth, invasion, and vascularization in a novel chick embryo brain tumor model. Clin. Exper. Metas., 22, 225-236.

Martin-DeLeon, P.A., H. Zhang, C. Morales, Y. Zhao, M. Rulon, B. Barnoski, H. Chen, and D.S. Galileo (2005). Spam1-associated transmission ratio distortion in mice: elucidating the mechanism. Reprod. Biol. and Endocrinol., 3, 32.

Morgan, J.C., J.E. Majors, and D.S. Galileo (2005). Distinct and opposite roles for SH2 and SH3 domains of v-src in embryo survival and hemangiosarcoma formation. Clin. Exper. Metas., 22, 167-175.

Castellini, M., L.V. Wolf, B.K. Chauhan, D.S. Galileo, M.W. Kilimann, A. Cvekl, M.K. Duncan (2005). Palm is expressed in both developing and adult mouse lens and retina. BMC Ophthalmol., Jun 21;5(1):14.

Stettler, E.M. and D.S. Galileo (2004). Radial glia produce and align the ligand fibronectin during neuronal migration in the developing chick brain. J. Comp. Neurol., 468, 441-451.

Galileo, D.S. (2003). Spatio-temporal gradient of oligodendrocyte differentiation in chick optic tectum requires brain integrity and cell-cell interactions. Glia, 41, 25-37.

Morgan, J.C., J.E. Majors, and D.S. Galileo (2000). Wild-type and mutant forms of v-src differentially alter neuronal migration and differentiation in vivo. J. Neurosci Res., 59(2), 226-237.

Galileo, D.S., K. Hunter, and S.B. Smith (1999). Stable and efficient gene transfer into the mutant retinal pigment epithelial cells of the Mitfvit mouse using a lentiviral vector. Current Eye Res., 18(2), 135-142.

Zhang, Z. and D.S. Galileo (1998b). Retroviral transfer of antisense integrin a6 or a8 sequences results in laminar redistribution or clonal cell death in developing brain. J. Neurosci., 18(17), 6928-6938.

Zhang, Z. and D.S. Galileo (1998a). Widespread programmed cell death in early developing chick optic tectum. NeuroReport, 9(12), 2797-2801.

Jackson, W.H., H. Moscoso, J. Nechtman, K.D. Lanclos, D.S. Galileo, and F.A. Garver (1998). Inhibition of HIV-1 replication by a b-galactosidase/ anti-tat hammerhead ribozyme fusion construct. Biochem. Biophys. Res. Comm., 245(1), 81-84.

Zhang, Z. and D.S. Galileo (1997). Direct in situ end labeling for detection of apoptotic cells in tissue sections. BioTechniques, 22(5), 834-836.

Galileo, D.S., J. Majors, A.F. Horwitz, and J.R. Sanes (1992). Retrovirally-introduced antisense integrin RNA inhibits neuroblast migration in vivo. Neuron, 9, 1117-1131.

Galileo, D.S. and P.J. Linser (1992). Immunomagnetic removal of neurons from developing chick optic tectum results in glial phenotypic instability. Glia, 5, 210-222.

Galileo, D.S., A.P. Gee, and P.J. Linser (1991). Neurons are replenished in cultures of embryonic chick optic tectum after immunomagnetic depletion. Dev. Biol., 146, 278-291.

Galileo, D.S., G.E. Gray, G.C. Owens, J. Majors, and J.R. Sanes (1990). Neurons and glia arise from a common progenitor in chick optic tectum: demonstration with two retroviruses and cell type-specific antibodies. Proc. Natl. Acad. Sci. USA, 87, 458-462.

Galileo, D.S. and J.B. Morrill (1985). Patterns of cells and extracellular material of the sea urchin Lytechinus variegatus (Echinodermata; Echinoidea) embryo, from hatched blastula to late gastrula. J. Morph., 185, 387-402.

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