Molecular and Developmental Biology
Faculty research interests in the area of molecular and developmental biology include developmental biology and cell signaling (Eivers Lab), molecular mechanisms in vertebrate development (Nissen Lab) and molecular regulatory mechanisms of development (Sharp Lab). An asterisk following a name in a publication citation indicates a student coauthor.
|Contact: Edward Eivers, Ph.D.|
Office: ASCL 392, ext: 3-2075
Laboratory: ASCL 350, ext: 3-2071
|Fluorescent immunostaining of phosphorylated Mad in the dorsal most cells of a Drosophila blastoderm embryo. Phosphorylated Mad represents the cells which receive high levels of BMP signals. BMP target genes are strongly activated in this region.|
My research lab investigates signaling crosstalk between the bone morphogenetic protein (BMP) and Wnt signaling pathways during Drosophila and Xenopus embryonic development. Both signaling pathways are evolutionarily conserved from flies to mammals and regulate a diverse range of biological events. These include stem cell maintenance, cell differentiation and organogenesis, while abnormal signaling of either pathway has strongly been linked to various forms of cancer. I am particularly interested in how the transcription factor Mad, which is required for both BMP and Wnt signaling, determines cell fate and differentiation during early tissue development.
|Eivers, E., Demagny, H., Choi, R.H., and De Robertis, E.M. 2011. Phosphorylation of Mad controls competition between Wingless and BMP signaling. Science Signaling 4: ra68.|
|Eivers, E., Demagny, H., and De Robertis, E.M. 2010. Integration of BMP and Wnt signaling pathways via vertebrate Smad1/5/8 and Drosophila Mad. Cytokine and Growth Factor Reviews 20: 357-365.|
|Eivers, E., Fuentealba, L., Sander, V., Clemens, J.C., Hartnett, L., and De Robertis, E.M. 2009. Mad is required for Wingless signaling in wing development and segment patterning in Drosophila. PLoS ONE 4: e6543.|
|Fuentealba, L.C., Eivers, E., Geissert, D., Taelman, V., and De Robertis, E.M. 2008. Asymmetric mitosis: Unequal segregation of proteins destined for degradation. Proceedings of the Nationall Academy of Sciences USA 105: 7732-7737.|
|Fuentealba, L.C., Eivers, E., Ikeda, A., Hurtado, C., Kuroda, H., Pera, E.M., and De Robertis, E.M. 2007. Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell 131: 980-993.|
|Contact: Robert Nissen, Ph.D.|
Office: ASCL 216, ext: 3-2309
Laboratory: ASCL 210, ext: 3-2093
|Example of a wild type zebrafish embryo at 28 hours. Zebrafish are used as a model organism for studying the molecular mechanisms of vertebrate development.|
Our long-term goal is to understand the mechanisms by which an initially pluripotent cell becomes restricted to specific fates and subsequently how it is maintained in the differentiated state. Currently, our focus is aimed at revealing the roles that the Wdr68 and Dyrk1b proteins play in the Nodal signaling pathway using zebrafish as a model organism. Ultimately, we hope these studies will shed new and valuable light on the mechanisms driving cell specification and differentiation in vertebrates.
|Mazmanian, G.*, Kovshilovsky, M.*, Yen, D.*, Mohanty, A.*, Mohanty, S.*, Nee, A., and Nissen, R.M. 2010. The zebrafish dyrk1b gene is important for endoderm formation. Genesis 48: 20.|
|Nissen, R.M., Amsterdam, A., and Hopkins, N. 2006. A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression. BMC Developmental Biology 6: 28.|
|Mansfield, J.H., Harfe, B.D., Nissen, R.M., Obenauer, J., Srineel, J., Chaudhuri, A., Farzan-Kashani, R., Zucker, M., Pasquinelli, A.E., Ruvkin, G., Sharp, P.A., Tabin, C.J., and McManus, M.T. 2004. MicroRNA-responsive "sensor" transgenes reveal Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nature Genetics 36: 1079-1083.|
|Amsterdam, A., Nissen, R.M., Sun, Z., Swindell, E.C., Farrington, S., and Hopkins, N. 2004. 315 genes essential for early zebrafish development. Proceedings of the National Academy of Sciences 101: 12792-12797.|
|Nissen, R.M., Yan, J., Amsterdam, A., Hopkins, N., and Burgess, S. 2003. Zebrafish foxi one modulates cellular responses to FGF signaling required for the integrity of ear and jaw patterning. Development 130: 2543-2554.|
|Contact: Sandra Sharp, Ph.D.|
Office: ASCL 316, ext: 3-2072
Laboratory: ASCL 328, ext: 3-4820
|AlexaFluor immuno-stained muscle fibers in a section of normal mouse hindlimb. Both cross and nearly longitudinal views are visible.|
An important goal in biomedical research is to understand the molecular pathways and mechanisms that regulate development, particularly those that regulate the transition from cell proliferation to cell differentiation. Our model system is muscle development or myogenesis. We currently have two major projects supported by grant funding from the National Institutes of Health. The first uses whole animals and molecular studies to test the hypothesis that either the generally expressed tumor suppressor transcription factor p53 or the muscle-specific transcription factor MyoD must be expressed for successful completion of myogenesis in vivo. The second uses an ultra-high throughput ChIP-Seq approach to understand the regulatory mechanisms involved in controlling binding of MyoD to DNA as cells stop dividing and develop into muscle. We aspire to contribute to the understanding of the mechanisms that regulate normal differentiation in order to enable the development of successful medical approaches to both developmental disorders and cancer.
|Krilowicz, B., Johnston, W., Sharp, S.B., Warter-Perez, N., Momand, J. 2007. A summer program designed to educate college students for careers in bioinformatics. CBE-Life Sciences Education 6: 74-83.|
|Sharp, S.B., Villalvazo, M., Espinosa, A., Damle, S., Padilla, X., Hartono, J., Gonzalez, R., and Vu, S. 2002. BC3H1 myogenic cells produce an infectious ecotropic murine leukemia virus. In Vitro Cellular & Developmental Biology-Animal 38: 378-381.|
|Sharp, S.B., Villalvazo, M., Huang, M., Gonzalez, R., Alarcon, I., Bahamonde, M., D'Agostin, D.M., Damle, S., Espinosa, A., Han, S.J., Liu, J., Navarro, P., Salguero, H., Son, J., and Vu, S. 2002. Further characterization of BC3H1 myogenic cells reveals lack of p53 activity and underexpression of several p53 regulated and extracellular matrix-associate gene products. In Vitro Cellular & Developmental Biology-Animal 38: 382-393.|
|Green, N., Vu, S., Farahmand, S., and Sharp, S.B. 1999. Limited T4 exonuclease activity and partial fill-in expand insertion site options for PCR subcloning. Biotechniques 27: 914-916.|
|McQueen, N.L, and Sharp, S.B. 1999. Molecular Diagnostics—an upper division/graduate course. Biochemical Education 27: 145-149.|
Note: ASCL = Wallis Annenberg Integrated Science Complex-Wing A (La Kretz Hall). When calling from off-campus, the area code and prefix for all telephone extensions is (323) 34X-XXXX.