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One or more keywords matched the following properties of Du, Wei
keywords Drosophila
overview Rb Tumor Suppressor, Control of Cell Proliferation and Differentiation 1) Novel approaches to target the loss of tumor suppressors in cancers The success of cancer therapies generally depend on their ability to target certain unique requirements of the cancer cells that are distinct from those of the normal cells. Current targeted cancer therapies at different stages of development mostly focus on inhibiting the deregulated oncogenic pathways kinases in cancers. In addition to deregulated oncogenic activation, cancer cells also often have inactivation of tumor suppressors. However such knowledge has yet to be exploited to develop targeted cancer therapies due to a lack of approaches to restore the lost tumor suppressor function in all the cancer cells and a lack of knowledge about the genes that are synthetic lethal with the lost tumor suppressors. While it is possible to carry out genome-wide RNAi screen to identify genes that are synthetic lethal with Rb using cell culture assays, such screen will depend largely on the particular culture conditions and may or may not reflect the in vivo situations. Rb is a tumor suppressor that is often lost in cancers. Because the Rb/E2F pathway is highly conserved between flies and mammalian systems, we hypothesize that genes that are synthetic lethal with loss of Rb will be conserved between the two systems as well. In a genetic screen for genes that can modulate the consequences of Rb loss, we found that mutation of gig, the Drosophila TSC2 homolog, show synergistically increased cell death with loss of Rb. Interestingly, knockdown of TSC2 in human cancer cells blocks cancer cell growth and induced cell death dependent on the Rb status, suggesting that TSC2 can potentially be used to specifically target Rb mutant cancers. Research in the lab include further characterization of the mechanisms of synergistic cell death induction, identification of genes/pathways/chemical inhibitors that can enhance the specific cell death induction by TSC2 knockdown, developing assays to screen for small molecule inhibitors of TSC2 function, and carry out additional genetic screen to identify additional potential targets. 2) Molecular mechanisms that coordinate the control of cell proliferation and differentiation during normal development We use the Drosophila developing eye as a model system to elucidate mechanisms by which developmental mechanisms coordinate cell proliferation and differentiation. In third instar eye discs, the morphogenetic furrow (MF), which is marked by an indentation in the eye disc, moves from posterior of the eye disc to the anterior. Cells anterior to the MF are asynchronously proliferating, which become cell cycle arrest in G1 in the MF. Photoreceptor differentiation initiates in the MF and the first photoreceptor determined is R8. R8 photoreceptor differentiation is controlled by the Atonal (Ato), a bHLH protein initially expressed in the MF and then restricted to the future R8 cells. Therefore one project in the lab is to elucidate the regulation of Ato expression, which is regulated by retinal determination genes and developmental signaling pathways. Cells in the MF and the differentiating photoreceptor clusters are arrested in G1. immediately posterior to the MF, cells not in the photoreceptor clusters undergo a synchronous round of cell cycle called second mitotic wave (SMW). Notch and EGFR signaling plays critical roles in controlling photoreceptor differentiation or cell proliferation. We are investigating the molecular mechanisms by which these developmental signaling pathways coordinate cell proliferation and differentiation.
One or more keywords matched the following items that are connected to Du, Wei
Item TypeName
Concept Drosophila melanogaster
Concept Drosophila Proteins
Academic Article Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E.
Academic Article Critical role of active repression by E2F and Rb proteins in endoreplication during Drosophila development.
Academic Article The evolution of courtship behaviors through the origination of a new gene in Drosophila.
Academic Article Retinoblastoma family protein promotes normal R8-photoreceptor differentiation in the absence of rhinoceros by inhibiting dE2F1 activity.
Academic Article Detecting novel low-abundant transcripts in Drosophila.
Academic Article Specific killing of Rb mutant cancer cells by inactivating TSC2.
Academic Article The role of RBF in developmentally regulated cell proliferation in the eye disc and in Cyclin D/Cdk4 induced cellular growth.
Academic Article Repression of dMyc expression by Wingless promotes Rbf-induced G1 arrest in the presumptive Drosophila wing margin.
Academic Article Drosophila chk2 plays an important role in a mitotic checkpoint in syncytial embryos.
Academic Article Control of cell cycle entry and exiting from the second mitotic wave in the Drosophila developing eye.
Academic Article Deregulated G1-S control and energy stress contribute to the synthetic-lethal interactions between inactivation of RB and TSC1 or TSC2.
Academic Article Proneural basic helix-loop-helix proteins and epidermal growth factor receptor signaling coordinately regulate cell type specification and cdk inhibitor expression during development.
Academic Article Direct control of the proneural gene atonal by retinal determination factors during Drosophila eye development.
Academic Article Wingless signaling directly regulates cyclin E expression in proliferating embryonic PNS precursor cells.
Academic Article Regulation of apoptosis of rbf mutant cells during Drosophila development.
Academic Article Mutation of the Apc1 homologue shattered disrupts normal eye development by disrupting G1 cell cycle arrest and progression through mitosis.
Academic Article The role of RBF in the introduction of G1 regulation during Drosophila embryogenesis.
Academic Article Hyperactivated Wnt signaling induces synthetic lethal interaction with Rb inactivation by elevating TORC1 activities.
Academic Article Suppression of the rbf null mutants by a de2f1 allele that lacks transactivation domain.
Academic Article Daughterless homodimer synergizes with Eyeless to induce Atonal expression and retinal neuron differentiation.
Academic Article A nutritional conditional lethal mutant due to pyridoxine 5'-phosphate oxidase deficiency in Drosophila melanogaster.
Academic Article DNA replication control through interaction of E2F-RB and the origin recognition complex.
Academic Article Drosophila Cdk4 is required for normal growth and is dispensable for cell cycle progression.
Academic Article Ectopic expression of dE2F and dDP induces cell proliferation and death in the Drosophila eye.
Academic Article Requirements for dE2F function in proliferating cells and in post-mitotic differentiating cells.
Academic Article RBF, a novel RB-related gene that regulates E2F activity and interacts with cyclin E in Drosophila.
Academic Article The homeodomain of Eyeless regulates cell growth and antagonizes the paired domain-dependent retinal differentiation function.
Academic Article Drosophila Chk2 is required for DNA damage-mediated cell cycle arrest and apoptosis.
Academic Article Groucho restricts rhomboid expression and couples EGFR activation with R8 selection during Drosophila photoreceptor differentiation.
Academic Article ESCRT-0 complex modulates Rbf-mutant cell survival by regulating Rhomboid endosomal trafficking and EGFR signaling.
Academic Article Loss of histone deacetylase HDAC1 induces cell death in Drosophila epithelial cells through JNK and Hippo signaling.
Academic Article RBF and Rno promote photoreceptor differentiation onset through modulating EGFR signaling in the Drosophila developing eye.
Academic Article Reversal of hyperactive Wnt signaling-dependent adipocyte defects by peptide boronic acids.
Grant Control of Cell Proliferation and Differentiation in the Developing Retina
Grant A novel approach to target Rb mutant cancers
Grant Regulation of EGFR Signaling in the Drosophila development
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  • Drosophila