Michael O'Connor, PhD
Howard Hughes Medical Institute Senior Investigator
The O'Connor laboratory is studying the function of several Drosophila genes to learn how interacting cells differentiate to form spatial patterns. One area of focus is to investigate how transcriptional regulation of the bithorax complex is controlled. The genes of the bithorax complex are responsible for specifying the identities of several segments of the fly. The working model is that much of the DNA within the complex contains large arrays of cis-acting control sequences that are organized into higher order structures referred to as "regulatory domains". The lab is using molecular and biochemical approaches to identify and purify the protein factors involved in controlling the formation of these regulatory domains.
The lab's second area of interest is to learn how cells communicate with one another during development. The particular group of signaling molecules that are studied are members of the TGF-ß family of secreted polypeptides. These effector molecules influence a wide variety of cellular processes including tissue growth, differentiation and cell death. My lab is using genetic and molecular methods to identify and clone genes that modulate the activity of these factors. The long term objective is to identify and characterize additional components of TGF-ß signal transduction systems so that we can understand the developmental functions of these factors in the context of a complete biochemical pathway.
The third area of interest is to understand how steroid hormones regulate early developmental processes. To this end the lab has identified a number of genes that regulate biosynthesis of ecdysone the major molting hormone in all insects. These genes are being characterized through genetic, molecular and biochemical manipulations.
Umulis, D. M., Shimmi, O., O'Connor, M. B., Othmer, H.G., (2010) Organism-scale modeling of early Drosophila development by Bone Morphogenetic Proteins. Dev. Cell in press
Okamoto*, N., Yamanaka* N., Yagi, Y.,, Nishida, Y., Kataoka, H., O’Connor, M.B., and Mizoguchi, Y. (2009) Fat body derived IGF-like peptide regulates post-feeding growth in Drosophila. Dev. Cell in press
Rewitz K.F., Yamanaka, N., Gilbert, L.I. and O’Connor M.B. (2009) Prothoracicotropic hormone activates the receptor tyrosine kinase Torso to initiate insect metamorphosis Science 326: 1403-5
Warren J.T., O'Connor M.B., Gilbert L.I. (2009) Studies on the Black Box: incorporation of 3-oxo-7dehydrocholesterol into ecdysteroids by Drosophila melanogaster and Manduca sexta. Insect Biochem Mol Biol. 39: 677-87
Jensen, P.A. and Zheng, X. Lee, T. and O’Connor M.B. (2009) The Drosophila Activin-like ligand Dawdle signals preferentially through a specific isoform of the Type-I receptor Baboon. Mechanism of Development 126: 950-7
Umulis, D.M., O’Connor, M.B., and Blair, S.S, (2009) Extracellular regulation of BMP signaling. Development 136: 3715-3728
Howe K.A., Watson. A.L., Dimitroff, B.D., Campion, B.K., O'Connor, M. B., Neufeld, T.P., Selleck, S.B. (2009) Dietary Rescue of Neurodevelopmental Deficits in a Drosophila Model of Tuberous Sclerosis in press J. of Neuroscience
Merino, C., González, M., Penney, J., Moujahidine, M., O’Connor, M.B., Verheyen E.M., and Haghighi, P. (2009) Nemo kinase interacts with Mad to coordinate synaptic growth at the Drosophila NMJ. Journal of Cell Science 185: 713-725
Rewitz, K. F., Larsen, M R., Lobner-Olesen, A., Rybczynski, R., O’Connor, M. B., Gilbert, L.I. (2009) A Phosphoproteomics Approach to Elucidate Neuropeptide Signal Transduction Controlling Insect Metamorphosis 39: 475-483 Insect Molec Bio. and Biochem.
Carlson, E.S., Tkac, I., Mafid, R., O’Connor, M.B., Andrews, N.C., Schallert, T., Gunshin, H., Petryk, A., and Georgieff, M.K. (2009) Iron is Essential for Neuron Development and Memory Function in Mouse Hippocampus. J. Nutrition 139: 672-9
Serpe, M., Umulis, D., Ralston, A., Chen, J., Olson, D.J., Avanesov, A., Othmer, H., O’Connor , M.B., and Blair, S.S. (2008) The BMP binding protein Cv-2 is a short range, concentration dependant biphasic modulator of BMP signaling. Dev. Cell 14: 940-953
Zhu, C., Boone, J., Jensen, P.A., Hann, S., Podemski, L., Locke, J., Doe, C.Q., and O’Connor, M.B. (2008) Drosophila dActivin and the Activin-Like product Dawdle function redundantly to regulate proliferation in the Drosophila larval brain. Development 135: 513-521
Zhu, C., Bornemann, D., Zhitomirsky, D., Miller, E., O’Connor M.B., and Simon, J.A., (2008) Drosophila Histone Decetylase-3 Controls Imaginal Disc Size Through Suppression of Apoptosis, PLOS Genetics, 4(2) e1000009
Umulis, D., O’Connor, M.B. and Othmer, H. (2007) Robustness of Embryonic spatial patterning in Drosophila melanogaster. Curr. Top. Dev. Biol. 81: 65-111
Ting, C-Y., Herman, T., Yonekura, S., Gao, S., Wang, J., Serpe, M., O’Connor, M.B., Zipursky, S.L., and Lee C-H. (2007) Tiling of R7 axons in the Drosophila Visual System is mediated both by transduction of Activin signaling to the nucleus and by mutual repulsion. Neuron, 56: 293-806
McBrayer, Z., Ono, H.*, Shimell, MJ, Parvy, J.-P., Beckstead, R.B., Warren, J.T., Thummel, C.S., Dauphin-Villemant, C., Gilbert, L.I., and O’Connor, M.B. (2007) Prothoracicotropic hormone regulates developmental timing and body size in Drosophila. Dev. Cell 13: 857-871
Sun, M., Thomas, M.J., Herder, R., Selleck, S.B., O'Connor, M.B., (2007) Presynaptic contributions of Chordin to hippocampal plasticity and spatial learning. J. Neuroscience 27: 740-50
Knox, S.,*, Ge* H., Ren, Y. Dimitroff, B.D., Howe, K.A.. Arsham, A.M., Easterday, M.C., Neufeld, T.P., O’Connor M.B., Selleck., S.B. (2007) Mechanisms of TSC-mediated Control of Synapse Assembly and Axon Guidance. Plos One , 2(4): e 375
Rewitz K.F., O’Connor M.B., and Gilbert L.I. Evolution of the insect Halloween family of cytochrome P450s: phylogeny, gene organization and functional conservation. (2007) Insect Biochem and Mol Bio 37: 741-53
Serpe, M. and O’Connor M.B. The metalloprotease Tolloid-related regulates Drosophila motoneuron axon guidance by activating latent TGF-ß type ligands. (2006) Development 133: 4969-79
Takaesu, N.T., Huyman-Walsh, C., Ye, L., Wisotzkey, R.G., Stinchfield, M.J., O’Connor M.B., Wotton, D., and Newfeld, S.J. dSno facilitates baboon signaling in the Drosophila brain by switching the affinity of Medea away from Mad towards dSmad2. (2006) Genetics, 174:1299-313
Umulis, D., Serpe, M. O’Connor, M.B. and Othmer, H. (2006) Robust, bistable patterning of the dorsal surface of the Drosophila embryo. Proc. Nat. Acad. Sci. 103: 11613-8
Ono, H., Rewitz, K., Shinoda, T., Itoyama., K., Petryk, A., Rybczynski, R., Jarcho, M., Warren, J.T., Marqués, G.M., Shimell, M., Gilbert, L.I., O’Connor, M.B. ( Oct. 2006) Spook and Spookier code for stage specific components of the ecdysone biosynthetic pathway in Diptera. Devel. Biol. 298: 555-70
Serpe M, Ralston A, Blair S, and O'Connor MB (2005) Matching cataltic activity to developmental function: Tlr processes Sog to help spcify the posterior crossvein in the Drosophila wing. Development 132: 2645-56.
Jadrick, J. L., O’Connor, M.B., and Coucouvanis, E. (2006) The TGF-ß activated kinase, TAK1, acts downstream of the TGF type I receptor, ALK1, to regulate vascular development in vivo. Development 133: 1529-41.
O’Connor, M.B., Umulis, D., Othmer, H., and Blair, S.S. (2006) Shaping BMP morphogen gradients in the Drosophila embryo and pupal wings. Development, 133: 183-93
Warren, J.T. Tank, L., Restifo L., Shimell, MJ., O'Connor, M.B., and Lawrence I. Gilbert. (2006) Discrete pulses of molting hormone, 20-hydroxyecdysone, during late larval development of Drosophila melanogaster: correlations with changes in gene activity. Developmental Dynamics 235: 315-26
Takaesu, N.T., Herbig, E.J., Zhitomersky, D., Johnson, A.N., O’Connor, M.B., and Newfeld S. J. (2005) DNA-binding domain mutations in SMAD genes yield dominant-negative proteins or a neomorphic protein that can activate WG target genes in Drosophila. Development, 132: 4882-94
Jorgenson, L.A., Sun, M., OConnor M.B., and Georgieff, M.K. (2005) Fetal Iron Deficiency Disrupts the Maturation of Synaptic Efficacy in Area CA1 of the Developing rat Hippocampus. Hippocampus, 15: 1094-102
Shimmi, O., Ralston, A., Blair, S., and O’Connor, M.B., (2005) Crossveinless codes for a new member of the Twisted gastrulation family required for producing peak levels of BMP signaling in the posterior crossvein of the Drosophila wing. Dev. Biol. 282: 70-83
Harumoto, T., Sakurai, K., Nakajima, M., Ueda, R., Saigo, K., O’Connor M.B., Nakato,H., Adachi-Yamada, T. (2005) Drosophila Spineless induces homeosis-dependent apoptotic and Hedgehog-mediated survival signals. Mol. Cell. Bio 25: 3140-50
Shimmi, O., Umulis, D., Othmer, H. and O’Connor M.B. (2005) Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo. Cell, 120: 873-876
Parvy, J-P., Blais, C., Bernard F. , Warren J., Petryk A., Gilbert L.I., O'Connor
M.B and Dauphin-Villemant, C. (2005) A role for ßFTZ-F1 in regulating ecdysteroidtiters during post-embryonic development in Drosophila melanogaster. Dev. Biol 282: 84-94
Petryk, A., Shimmi, O. Tervonen, L., Jarcho, M., O’Connor M. B., and Gopalakrishnan, R., (2005) Twisted gastrulation inhibits differentiation and mineralization in MC3t3-E1 osteoblast-like cells. Bone 36: 617-26
Warren JT, Petryk A, Zhirtimersky D, Marques G, Parvy J-P, Dauphin-Vilemant C, O'Connor MB, and Gilbert LI (2004) Phantom is the Drosophila P450 enzyme that mediates the 25-hydroxylation of 2,22,25 deoxyecdysone to 2,22 deoxyecdysone. J. of Insect Biochem. and Mol. Bio. 34:991-101.
Johnson KG, Epstein E, Lincecum J, O'Connor MB and Van Vactor D (2004) The heparan sulfate proteoglycan Syndecan is required for midline guidance in the Drosophila central nervous system. Current Biology 14:499-504.
McCabe B, Hom S, Aberle H, Marques G, Haerry T, Wan H, MB O'Connor and CS Goodman and AP Haghighi (2004) Highwire regulates a presynaptic BMP signaling cascate essential fro synaptic growth. 241:891-905
Petryk A, Anderson RM, Jarcho MP, Leaf I, Carlson CS, Kingensmith J, Shawlot W, MB O'Connor (2004) The mammalian twisted gastrulation gene functions in foregut and craniofacial development. Development Biolgoy in 267:374-386.
Petryk A*, Warren JT*, Marques G, Jarcho MP, Parvy J-P, Dauphin-Vilemant C, Gilbert LI, and O'Connor MB (2003) Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone. Proc Nat. Acad Sci. USA 100:13773-8.
Jadrich, J., O’Connor M.B. and Descotte, V., An Overview of TGF-ß signaling. In “Inborn Errors of Development” 2nd Edition (2007) Ed. Epstein, C. , Erickson R.P., and Wynshaw-Boris, A. Oxford University Press in press
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