Dr. Timothy Megraw
Associate Professor of Biomedical Sciences & Neuroscience
- Biomedical Sciences
- MSR 3300
- The Megraw lab investigates the functions of centrosomes and cilia in cell division, development and disease using Drosophila, mouse, and human cell culture models. This includes asymmetric division of stem cells, the regulation of centrosomal and other microtubule-organizing centers (MTOCs), metabolic disorders due to loss of centrosome proteins, and regulation of primary cilium assembly and function. Centrosome-based disorders that impact stem cell function and brain development are a major focus of our research.
- Current Research
- The centrosome is the major microtubule-organizing center (MTOC) in animal cells and impacts many disease-related functions. We focus on the links between centrosome functions and inherited forms of microcephaly that arise from syndromes such as MCPH or SCKL. Our investigations show cell division-related defects in stem cells arising from impaired centrosome replication, but there are also specific metabolic impairments in cells mutant for centrosome protein genes. We suspect that Zika virus perturbs the same centrosome-related pathways in human neural stem cells, causing microcephaly in infected mothers during their pregnancy. We are investigating the links between Zika virus infection and centrosome impairment, to connect the inherited and viral-induced forms of microcephaly.
- Recent Publications
Chen JV, Buchwalter RA, Kao LR, Megraw TL, A splice variant of centrosomin converts mitochondria to microtubule- organizing centers, Curr Biol, 2017 PubMed Manojlovic Z, Earwood R, Kato A, Perez D, Cabrera OA, Didier R, Megraw TL, Stefanovic B, Kato Y, La-related protein 6 controls ciliated cell differentiation , Cilia, 2017 PubMed Jana SC, Bettencourt-Dias M, Durand B, Megraw TL., Drosophila melanogaster as a model for basal body research., Cilia, 2016 PubMed Zheng Y, Mennella V, Marks S, Wildonger J, Elnagdi E, Agard D, Megraw TL, The Seckel syndrome and centrosomal protein Ninein localizes asymmetrically to stem cell centrosomes but is not required for normal development, behavior, or DNA damage response in Drosophila., Mol Biol Cell, 2016 PubMed Guarderas F, Leavell Y, Sengupta T, Zhukova M, Megraw TL, Assessment of Chicken-Egg Membrane as a Dressing for Wound Healing, Adv Skin Wound Care, 2016 PubMed Jodeiri Farshbaf M, Ghaedi K, Megraw TL, Curtiss J, Shirani Faradonbeh M, Vaziri P, Nasr-Esfahani MH, Does PGC1alpha/FNDC5/BDNF Elicit the Beneficial Effects of Exercise on Neurodegenerative Disorders?, Neuromolecular Med, 2016 PubMed Debec A, Megraw TL, Guichet A, Methods to establish drosophila cell lines, Methods Mol Biol, 2016 PubMed Bingol K, Li DW, Bruschweiler-Li L, Cabrera OA, Megraw T, Zhang F, Brüschweiler R, Unified and isomer-specific NMR metabolomics database for the accurate analysis of (13)C-(1)H HSQC spectra, ACS Chem Biol, 2015 PubMed Man X, Megraw TL, Lim YP, Cep68 can be regulated by Nek2 and SCF complex, Eur J Cell Biol, 2015 PubMed Tözser J, Earwood R, Kato A, Brown J, Tanaka K, Didier R, Megraw TL, Blum M, Kato Y, TGF-beta Signaling Regulates the Differentiation of Motile Cilia, Cell Rep, 2015 PubMed Chen JV, Kao LR, Jana SC, Sivan-Loukianova E, Mendonça S, Cabrera OA, Singh P, Cabernard C, Eberl DF, Bettencourt-Dias M, Megraw TL, Rootletin organizes the ciliary rootlet to achieve neuron sensory function in Drosophila, J Cell Biol, 2015 PubMed Chen JV, Megraw TL, Spermitin: a novel mitochondrial protein in Drosophila spermatids, PLoS One, 2014 PubMed Chen JV, Megraw TL, Mother centrioles do a cartwheel to produce just one daughter, Dev Cell, 2014 PubMed Galletta BJ, Guillen RX, Fagerstrom CJ, Brownlee CW, Lerit DA, Megraw TL, Rogers GC, Rusan NM, Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies, Mol Biol Cell, 2014 PubMed Riparbelli MG, Cabrera OA, Callaini G, Megraw TL, Unique properties of Drosophila spermatocyte primary cilia, Biol Open, 2013 PubMed Chen JV, Megraw TL, Cenexin1 and Odf2: splice variants with diverged cilium functions, Cell Cycle, 2013 PubMed Kao LR, Megraw TL, Cytokinesis: RhoGEFs control a developmental cleavage switch, Curr Biol, 2012 PubMed Riparbelli MG, Callaini G, Megraw TL, Assembly and persistence of primary cilia in dividing Drosophila spermatocytes, Dev Cell, 2012 PubMed Megraw TL, Sharkey JT, Nowakowski RS, Cdk5rap2 exposes the centrosomal root of microcephaly syndromes, Trends Cell Biol, 2011 PubMed Megraw TL, PP2A targets SAS-5 in centriole assembly, Dev Cell, 2011 PubMed Gopalakrishnan J, Mennella V, Blachon S, Zhai B, Smith AH, Megraw TL, Nicastro D, Gygi SP, Agard DA, Avidor-Reiss T, Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome, Nat Commun, 2011 PubMed Barrera JA, Kao LR, Hammer RE, Seemann J, Fuchs JL, Megraw TL, CDK5RAP2 regulates centriole engagement and cohesion in mice, Dev Cell, 2010 PubMed Kao LR, Megraw TL, Centrocortin cooperates with centrosomin to organize Drosophila embryonic cleavage furrows, Curr Biol, 2009 PubMed Mottier-Pavie V, Megraw TL, Drosophila bld10 is a centriolar protein that regulates centriole, basal body, and motile cilium assembly, Mol Biol Cell, 2009 PubMed Kotadia S, Kao LR, Comerford SA, Jones RT, Hammer RE, Megraw TL, PP2A-dependent disruption of centrosome replication and cytoskeleton organization in Drosophila by SV40 small tumor antigen, Oncogene, 2008 PubMed Zhang J, Megraw TL, Proper recruitment of gamma-tubulin and D-TACC/Msps to embryonic Drosophila centrosomes requires Centrosomin Motif 1, Mol Biol Cell, 2007 PubMed Kao LR, Megraw TL, RNAi in cultured Drosophila cells, Methods Mol Biol, 2004 PubMed Megraw TL, Kilaru S, Turner FR, Kaufman TC, The centrosome is a dynamic structure that ejects PCM flares, J Cell Sci, 2002 PubMed Megraw TL, Kao LR, Kaufman TC, Zygotic development without functional mitotic centrosomes, Curr Biol, 2001 PubMed Megraw TL, Kaufman TC, The centrosome in Drosophila oocyte development, Curr Top Dev Biol, 2000 PubMed Megraw TL, Li K, Kao LR, Kaufman TC, The centrosomin protein is required for centrosome assembly and function during cleavage in Drosophila, Development, 1999 PubMed Li K, Xu EY, Cecil JK, Turner FR, Megraw TL, Kaufman TC, Drosophila centrosomin protein is required for male meiosis and assembly of the flagellar axoneme, J Cell Biol, 1998 PubMed Cho JH, Ha SJ, Kao LR, Megraw TL, Chae CB, A novel DNA-binding protein bound to the mitochondrial inner membrane restores the null mutation of mitochondrial histone Abf2p in Saccharomyces cerevisiae, Mol Cell Biol, 1998 PubMed Megraw T, Kaufman TC, Kovalick GE, Sequence and expression of Drosophila Antigen 5-related 2, a new member of the CAP gene family, Gene, 1998 PubMed Kao LR, Megraw TL, Chae CB, SHM1: a multicopy suppressor of a temperature-sensitive null mutation in the HMG1-like abf2 gene, Yeast, 1996 PubMed Megraw TL, Kao LR, Chae CB, The mitochondrial histone HM: an evolutionary link between bacterial HU and nuclear HMG1 proteins, Biochimie, 1994 PubMed Kao LR, Megraw TL, Chae CB, Essential role of the HMG domain in the function of yeast mitochondrial histone HM: functional complementation of HM by the nuclear nonhistone protein NHP6A, Proc Natl Acad Sci U S A, 1993 PubMed Megraw TL, Chae CB, Functional complementarity between the HMG1-like yeast mitochondrial histone HM and the bacterial histone-like protein HU, J Biol Chem, 1993 PubMed