My lab’s primary area of interest in the lab to learn how cells communicate with one another during development. One group of signaling molecules that we study are the TGF-ß family of secreted polypeptides. This is the largest family of secreted "growth" factors with 33 members in vertebrates including TGF-ßs, Activin/Inhibins and bone morphogenetic proteins (BMPs). These signaling factors influence a wide variety of cellular processes including tissue growth, differentiation, and death as well as metabolic and synaptic homeostasis. My lab is using genetic, molecular, biochemical and computational methods to analyze of these factors influence these important biological processes. Three recent areas of interest are to 1) determine the mechanisms responsible for trafficking of TGF-ß receptors to different locations in the cell 2) to identify targets of TGF-ß signaling that regulate cytoskeletal dynamics in developing tissues and 3) identify targets of TGF-ß signaling that regulate metabolic aspects of development and sensitivities to different nutrient sources.
The second general area of interest in the lab is to understand how timing of developmental processes is regulated. In many organisms systemically delivered steroid hormones modulate developmental transitions, including metamorphosis in insects and puberty in humans. We wish to identify the neuroendocrine signals that trigger steroid production and release in the fruit fly and we are also interested in characterizing the cell biology of steroid production and secretion in endocrine cells, including determining how biosynthetic intermediates are trafficked between the mitochondria and the ER and how steroids are exported and imported into tissues.
Pisansky, M., Young, A.E., O'Connor, M.B., Gottesman, I.I., Bagchi, A., Gewirtz, J.C., (2017) Mice lacking the chromodomain helicase DNA-binding 5 chromatin remodeler display characteristics of autism. in press Translational Psychiatry
Kalpana Makhijani, K., BAlexander, B., Rao, D., Petraki, S., Herboso, L., Kukar, K., Batool, I., Wachner, S., Gold, K.S., Wong, C., O’Connor, M.B., and Brückner, K., (2017) An inducible signal from sensory neurons regulates the self renewing blood cell pool in Drosophila. (in press Nat. Cell Bio.)
Song W, Cheng D, Hong S, Sappe B, Hu Y, Wei N, Zhu C, O'Connor MB, Pissios P, Perrimon N. (2017) Migut Derived Activin Regulates Glucagon-like Action in the Fat Body and Glycemic Control. Cell Metab. 2017 Feb 7;25(2):386-399. doi: 10.1016/j.cmet.2017.01.002.
Upadhyay, A.,* Kim, M-J*, Moss-Taylor, L.,* Ghosh, A.C.,* and O’Connor, M.B., (2017) TGF-beta Family Signaling in Drosophila, Cold Spring Harbor Perspective Jan 27. pii: a022152. doi: 10.1101/cshperspect.a022152. [Epub ahead of print]
Schiesari, L., Andreatta, G., Kyriacou, C.P., O’Connor, M.B., and Costa, R. (2016) The Insulin-like Proteins dILPs-2/5 determine diapause inducibility in Drosophila. Plos One Sep 30;11(9):e0163680. doi: 10.1371/journal.pone.0163680.
Ou Q, Zeng J, Yamanaka, N., Brakken-Thal, C., O'Connor, M.B., King-Jones K. (2016) The insect prothoracic Gland as a Model for Steroid Hormone Biosynthesis and Regulation. Cell Reports, 16: 247-62
Moeller, E.,M., Danielsen, T., Yamanaka, N. Laursen, J.M., Sønderholm, C., Kondo, S., Harvald, E.B., Faergeman, N.J., Haley, M.J., O’Connor, K.A., King-Jones, K., O’Connor, M.B., Kim F. Rewitz (2016) A genome-wide in vivo screen in Drosophila identifies conserved regulators of cholesterol trafficking and steroid synthesis. Dev Cell 37: 558-70
Komura-Kaawa, T., Hirota, K., Shimada-Niwa, Y., Yamauchi, R., Shinoda, T., Fukamizu, A., Shimell, M., O’Connor, M.B. and Niwa, R. (2015) The Drosophila Zinc finger transcription factor Ouija board regulates ecdysteroidogenesis via transcriptional control of spookier Plos Genetics 11: e1005712.doi:10.1371 PMID 26658797
Yamanaka, N., Marques, G.M. and O’Connor, M.B., (2015) Vesicle-Mediated Steroid hormone Secretion in Drosophila melanogaster. Cell, 163(4): 907-1
Ghosh, A., Leof, E., Haley, M.J.,Shimell, M. and O’Connor M.B. (2015) UPRT, a suicide-gene therapy candidate in higher eukaryotes, is required for Drosophila larval growth and normal adult lifespan. Scientific Reports 5: 13176. doi: 10.1038/srep13176.
Bortle, K. V., Peterson, A.J., Takenaka, N., O’Connor,M.B., and Corces, V.G., (2015) CTCF-dependent co-localization of canonical Smad signaling factors at architectural protein binding sites in D. melanogaster" Cell Cycle 14(16): 2677-87. doi: 10.1080/15384101.2015.1053670
Fresan, U., Cuartero, S., O’Connor M.B. and Espinas, M.L., (2015) The insulator protein CTCF regulates Drosophila steriodogenesis Biology 15;4(7): 852-7. doi: 10.1242/bio.012344.)
Kim MJ, O'Connor MB. (2014) Anterograde Activin signaling regulates postsynaptic membrane potential and GluRIIA/B abundance at the Drosophila neuromuscular junction. PLoS One. Sep 25;9(9):e107443. doi: 10.1371/journal.pone.0107443. eCollection 2014.
Ghosh, A., and O’Connor, M.B. (2014) Systemic Activin signaling independently regulates sugar homeostasis, cellular metabolism, and pH balance in Drosophila. PNAS 111(15): 5729-34
Yamanaka, N.,* Romero, N.M.,* Martin, F.A.,* Rewitz, K.F., Sun, M., O’Connor, M.B. Léopold, P. (2013) Neuroendocrine control of Drosophila larval light preference Science 341: 1113-6 PMID: 24009394
Peluso, C.E., Umulis, D., Kim, D.Y-J., O’Connor, M.B., Serpe, M., (2011) The molecular basis for Sog-mediated diffusion of BMP ligands in Drosophila. Dev Cell 21: 375-83 PMID: 21839924
Rewitz, K. Yamanaka, N. and O’Connor M.B. (2010) Steroid hormone inactivation is required during the juvenile-adult transition in Drosophila Dev. Cell 19: 895-209
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 18: 260-274
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
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 17:885-891