Molecular and Developmental Biology
Faculty research interests in the area of molecular and developmental biology include developmental biology and cell signaling (Eivers Lab), mitochondrial systems biology (Lanning Lab), computational biophysics (Nerenberg 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.
Urrutia, H., Aleman, A. and Eivers E. 2016. Drosophila Dullard functions as a Mad phosphatase to terminate BMP signaling. Sci. Rep. 6, 32269; doi: 10.1038/srep32269
Aleman, A., Rios, M., Juarez, M., Lee, D., Chen, A. and Eivers, E. 2014. Mad linker phosphorylations control the intensity and range of the BMP-activity gradient in developing Drosophila tissues. Scientific Reports 4: 6927; DOI:10.1038/srep06927.
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.
|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: Nathan Lanning, Ph.D.
Office: ASCL 317, ext: 3-2092
Laboratory: ASCL 330, ext: 3-5159
|Fluorescently labeled human fibroblast cell, showing the mitochondria (green), the actin cytoskeleton (cyan), and the nucleus (magenta).|
The goal of our lab is to map mitochondrial proteins and functions to disease. Mitochondrial dysfunction is associated with many pathologies including cancer, neurodegenerative diseases, cardiovascular disease, and mitochondrial diseases. However, in many cases, the distinct mechanisms by which mitochondrial dysfunction promotes these diseases remain unknown. We utilize a synthesis of cell and molecular biology, biochemistry, and systems biology to characterize the functions of greater than 1,000 mitochondrial proteins and how these proteins and functions are related to disease.
|Lanning, N.J., Looyenga, B.D., Kauffman, A.L., Niemi, N.M., Sudderth, J., DeBerardinis, R.J., and MacKeigan, J.P. 2014. A mitochondrial RNAi screen defines cellular bioenergetics determinants and identifies adenylate kinase as a key regulator of ATP levels. Cell Reports 7: 907-917.|
|Niemi, N.M., Lanning, N.J., Westrate, L.M., and MacKeigan, J.P. 2013. Downregulation of the mitochondrial phosphatase PTPMT1 is sufficient to promote cancer cell death. PLoS One 8: e53803.|
|Niemi, N.M., Lanning, N.J., Klomp, J.A., Tait, S.W., Xu, Y., Dykema, K.J., Murphy, L.O., Gaither, L.A., Xu, H.E., Furge, K.A., Green, D.R., and MacKeigan, J.P. 2011. MK-STYX, a catalytically inactive phosphatase regulating mitochondrially dependent apoptosis. Molecular and Cellular Biology 31: 1357-1368.|
|Fogg, V.C., Lanning, N.J., and MacKeigan, J.P. 2011. Mitochondria in cancer: at the crossroads of life and death. Chinese Journal of Cancer 30: 526-539.|
|Lanning, N.J., Su, H.W., Argetsinger, L.S., and Carter-Su, C. 2011. Identification of SH2B1β as a focal adhesion protein that regulates focal adhesion size and number. Journal of Cell Science 124: 3095-3105.|
|Contact: Paul Nerenberg, Ph.D.
Office: coming soon, ext: coming soon
Laboratory: coming soon, ext: coming soon
|X-ray crystal structure of the transcription factor NikR bound to its operator DNA sequence. NikR is a tetrameric protein that requires four nickel (Ni2+, shown in magenta) ions to properly fold. It represses the transcription of the transmembrane nickel transporter, NikABCDE, in E. coli, H. pylori, and other bacteria to maintain an appropriate intracellular Ni2+ concentration.|
My group uses molecular dynamics (MD) simulations to understand the molecular mechanisms behind both regular and disease-associated physiological processes. A current interest is how DNA methylation may alter the conformational equilibrium of DNA and modulate transcription factor binding affinity. Other interests include understanding the effects of post-translational modifications on the conformational ensembles of proteins and how well current MD force fields can model the interactions of nucleic acids and physiologically-relevant ions (e.g., K+, Mg2+, Cl-, etc.).
|Yedvabny E, Nerenberg PS, So C, and Head-Gordon T. 2015. The Disordered Structural Ensembles of Vasopressin and Oxytocin and Their Mutants. Journal of Physical Chemistry B 119: 896-905.|
|Liguori N, Nerenberg PS, and Head-Gordon T. 2013. Embedding A?42 in Heterogenous Membranes Depends on Cholesterol Asymmetries. Biophysical Journal 105: 899-910.|
|Nerenberg PS and Head-Gordon T. 2011. Optimizing Protein-Solvent Force Fields to Reproduce Intrinsic Conformational Preferences of Model Peptides. Journal of Chemical Theory and Computation 7: 1220-1230.|
|Phillips CM, Nerenberg PS, Drennan CL, and Stultz CM. 2009. The Physical Basis of Metal Binding Specificity in E. coli NikR. Journal of the American Chemical Society 131: 10220-10228.|
|Nerenberg PS and Stultz CM. 2008. Differential Unfolding of ?1 and ?2 Chains in Type I Collagen and Collagenolysis. Journal of Molecular Biology 382: 246-256.|
|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.