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Deni S. Galileo, Ph.D.
- BISC 305* - Cell Physiology
- BISC 439/639* - Developmental Neurobiology
- BISC 850* - Microscopic Anatomy
- BISC 850* - Cancer and Development Journal Club
*Course web site available through MyCourses
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.
- Control of invasiveness of glioma tumor cells within brain via L1CAM.
- Control of metastasis of breast cancer cells to brain and other organs via L1CAM.
- Roles of integrins and extracellular matrix molecules in neuronal migration and survival in developing brain.
- Axon outgrowth on cells with patterned gene expression.
- Vishnu Mohanan - Graduate Student. Glioma tumor cell invasiveness and L1-binding receptors.
- Karma Pace McDuffy - Graduate Student (Delaware State University Neuroscience Program). Role of exosomes in glioma tumor cell invasiveness.
- Hamza Bhatti - Senior, Interactions of glioma tumor cells with brain cells.
- Becky Mongeau - Sophomore, Quantitative modeling of glioma cancer cell motility.
- Mohanan V, Temburni MK, Kappes JC, Galileo DS. L1CAM stimulates glioma cell motility and proliferation through the fibroblast growth factor receptor. Clin Exp Metastasis. 2012; Dec.1; epub ahead of print.
- Aravindan RG, Fomin VP, Naik UP, Modelski MJ, Naik MU, Galileo DS, Duncan RL, Martin-Deleon PA. CASK interacts with PMCA4b and JAM-A on the mouse sperm flagellum to regulate Ca(2+) homeostasis and motility. J Cell Physiol. 2012 Aug;227(8):3138-50.
- Yang M, Li Y, Chilukuri K, Brady OA, Boulos MI, Kappes JC, Galileo DS. L1 stimulation of human glioma cell motility correlates with FAK activation. J Neurooncol. 2011;105(1):27-44.
- Li Y, Galileo DS. Soluble L1CAM promotes breast cancer cell adhesion and migration in vitro, but not invasion. Cancer Cell Int. 2010;10:34.
- Reese KL, Aravindan RG, Griffiths GS, Shao M, Wang Y, Galileo DS, Atmuri V, Triggs-Raine BL, Martin-Deleon PA. Acidic hyaluronidase activity is present in mouse sperm and is reduced in the absence of SPAM1: evidence for a role for hyaluronidase 3 in mouse and human sperm. Mol reprod Dev. 2010;77(9):759–72.
- Sauers DJ, Temburni MK, Biggins JB, Ceo LM, Galileo DS, Koh JT. Light-Activated Gene Expression Directs Segregation of Co-cultured Cells in Vitro. ACS Chem Biol. 2010;5(3):313–20.
- Galileo DS, Patel VP. Tracking migrating cells with MetaMorph software. MetaMatters. 2009;1(4):1–3.
- Griffiths GS, Galileo DS, Aravindan RG, Martin-DeLeon PA. Clusterin Facilitates Exchange of Glycosyl Phosphatidylinositol-Linked SPAM1 Between Reproductive Luminal Fluids and Mouse and Human Sperm Membranes. Biol Reprod. 2009;81(3):562–70.
- Yang M, Adla S, Temburni MK, et al. Stimulation of glioma cell motility by expression, proteolysis, and release of the L1 neural cell recognition molecule. Cancer Cell Int. 2009;9:27.
- Farach AM, Galileo DS. O-GlcNAc modification of radial glial vimentin filaments in the developing chick brain. Brain Cell Biol. 2008;36(5-6):191–202.
- Griffiths GS, Galileo DS, Reese K, Martin-DeLeon PA. Investigating the role of murine epididymosomes and uterosomes in GPI-linked protein transfer to sperm using SPAM1 as a model. Mol Reprod Dev. 2008;75(11):1627–36.
- Griffiths GS, Miller KA, Galileo DS, Martin-DeLeon PA. Murine SPAM1 is secreted by the estrous uterus and oviduct in a form that can bind to sperm during capacitation: acquisition enhances hyaluronic acid-binding ability and cumulus dispersal efficiency. Reproduction. 2008;135(3):293–301.
- Tian J, Paquette-Straub C, Sage EH, et al. Inhibition of melanoma cell motility by the snake venom disintegrin eristostatin. Toxicon. 2007;49(7):899–908.
- Chen H, Griffiths G, Galileo DS, Martin-DeLeon PA. Epididymal SPAM1 is a marker for sperm maturation in the mouse. Biol Reprod. 2006;74(5):923–930.
- Fotos JS, Patel VP, Karin NJ, Temburni MK, Koh JT, Galileo DS. Automated time-lapse microscopy and high-resolution tracking of cell migration. Cytotechnology. 2006;51(1):7–19.
- Masiello LM, Fotos JS, Galileo DS, Karin NJ. Lysophosphatidic acid induces chemotaxis in MC3T3-E1 osteoblastic cells. Bone. 2006;39(1):72–82.
- Castellini M, Wolf LV, Chauhan BK, et al. Palm is expressed in both developing and adult mouse lens and retina. BMC Ophthalmol. 2005;5:14.
- Cretu A, Fotos JS, Little BW, Galileo DS. Human and rat glioma growth, invasion, and vascularization in a novel chick embryo brain tumor model. Clin Exp Metastasis. 2005;22(3):225–236.
- Martin-DeLeon PA, Zhang H, Morales CR, et al. Spam1-associated transmission ratio distortion in mice: elucidating the mechanism. Reprod Biol Endocrinol. 2005;3:32.
- Morgan JC, Majors JE, Galileo DS. Distinct and opposite roles for SH2 and SH3 domains of v-src in embryo survival and hemangiosarcoma formation. Clin Exp Metastasis. 2005;22(2):167–175.
- Stettler EM, Galileo DS. Radial glia produce and align the ligand fibronectin during neuronal migration in the developing chick brain. J Comp Neurol. 2004;468(3):441–451.
- Galileo DS. Spatiotemporal gradient of oligodendrocyte differentiation in chick optic tectum requires brain integrity and cell-cell interactions. Glia. 2003;41(1):25–37.
- Morgan JC, Majors JE, Galileo DS. Wild-type and mutant forms of v-src differentially alter neuronal migration and differentiation in vivo. J Neurosci Res. 2000;59(2):226–237.
- Galileo DS, Hunter K, Smith SB. Stable and efficient gene transfer into the mutant retinal pigment epithelial cells of the Mitf(vit) mouse using a lentiviral vector. Curr Eye Res. 1999;18(2):135–142.
- Jackson WHJ, Moscoso H, Nechtman JF, Galileo DS, Garver FA, Lanclos KD. Inhibition of HIV-1 replication by an anti-tat hammerhead ribozyme. Biochem Biophys Res Commun. 1998;245(1):81–84.
- Zhang Z, Galileo DS. Retroviral transfer of antisense integrin alpha6 or alpha8 sequences results in laminar redistribution or clonal cell death in developing brain. J Neurosci. 1998;18(17):6928–6938.
- Zhang Z, Galileo DS. Widespread programmed cell death in early developing chick optic tectum. Neuroreport. 1998;9(12):2797–2801.
- Zhang Z, Galileo DS. Direct in situ end-labeling for detection of apoptotic cells in tissue sections. Biotechniques. 1997;22(5):834–836.
- Galileo DS, Linser PJ. Immunomagnetic removal of neurons from developing chick optic tectum results in glial phenotypic instability. Glia. 1992;5(3):210–222.
- Galileo DS, Majors J, Horwitz AF, Sanes JR. Retrovirally introduced antisense integrin RNA inhibits neuroblast migration in vivo. Neuron. 1992;9(6):1117–1131.
- Galileo DS, Gee AP, Linser PJ. Neurons are replenished in cultures of embryonic chick optic tectum after immunomagnetic depletion. Dev Biol. 1991;146(2):278–291.
- Galileo DS, Gray GE, Owens GC, Majors J, Sanes JR. Neurons and glia arise from a common progenitor in chicken optic tectum: demonstration with two retroviruses and cell type-specific antibodies. Proc Natl Acad Sci U S A. 1990;87(1):458–462.
- Galileo DS, Morrill JB. Patterns of cells and extracellular material of the sea-urchin Lytechinus-variegatus (Echinodermata, Echinoidea) embryo, from hatched blastula to late gastrula. J Morphol. 1985;185(3):387–402.
Faculty Senate President-Elect
Phone: (302) 831-1277
Fax: (302) 831-2767
Office: 232 Wolf Hall
Lab: 248 Wolf Hall
Department of Biological Sciences
University of Delaware
Newark, DE 19716
- B.A. - New College of Florida
- Ph.D. - University of Florida College of Medicine and Whitney Laboratory
- Postdoctoral - Washington University School of Medicine (St. Louis)