Timothy Megraw Ph.D.
Professor
Biosketch
Professor
Member, Center for Brain Repair
Member, Neuroscience Program
Education
Postdoc, Molecular Genetics, Indiana University and the Howard Hughes Medical Institute
PhD, Biochemistry, The University of North Carolina at Chapel Hill
BS, Biochemistry, The State University of New York at Stony Brook
Service
Director, Postdoctoral Career Development Program
Faculty Recruitment committee
Graduate committee
Postdoc Training committee
Life Sciences Symposium steering committee
Proteomics users committee
Honors/Awards
Innovator Award, Florida State University (2011).
Outstanding Senior Faculty Researcher, Florida State University (2012)
Memberships
American Society for Cell Biology
Genetics Society of America
European Molecular Biology Organisation
Courses
Bioregulation
Modeling Human Disease
Foundations of Medicine 2
Integrated Clinical Sciences
Biomedical Techniques
Professional Development (Tools of the Trade)
Current Research in Biomedical Sciences (BMS4932)
Research Focus
--To see lab web page click HERE--
Research Interests: Centrosomes, cilia, stem cells, asymmetric cell division, neurodegeneration.
Centrosome function in cell division, development and disease
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 basis of MCPH: a neural stem cell disease.
We are investigating a group of 13 proteins whose genes are mutated in a syndrome called autosomal recessive primary microcephaly (MCPH). Mutations result in severe reduction of the cerebral cortex during embryonic development. We are investigating a new line of evidence that points to the mechanism for this disease.
• Metabolic control.
We are investigating a novel function for centrosome proteins in the control of metabolism. The metabolic regulation controlled by centrosome proteins is essential for neuronal function and survival, especially in the face of particular stresses.
• Conversion of mitochondria to MTOCs.
We discovered an alternative splice product of a centrosome protein that targets to the mitochondria. This protein assembles microtubule-organizing centers on the surface of mitochondria. This is a very novel non-centrosomal MTOC, and represents the first molecular characterization of mitochondrial MTOCs.
• Asymmetric centrosomal control of neural stem cell division.
In neural stem cells, we discovered an asymmetric centriole protein that localizes only to the younger daughter centrosome, and is inherited by the renewed stem cell at each division. This protein regulates stem cell polarity.
• Regulation of centriole duplication.
We are investigating a complex of proteins, including centrosomin, that regulate the 'licensing step' that governs centriole duplication during the cell cycle.
Publications
Complete list: https://www.ncbi.nlm.nih.gov/myncbi/timothy.megraw.1/bibliography/public/
Buchwalter RA Ogden SC, York SB, Sun L, Zheng C, Hammock C, Cheng Y, Chen JV, Cone AS, Meckes DG, Tang H, Megraw TL
Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers.
Cells. doi: 10.3390/cells10123335 (2021).
Debec A, Loppin B, Zheng C, Liu X, Megraw TL
The Enigma of Centriole Loss in the 1182-4 Cell Line.
Cells. 9(5): E1300. doi: 10.3390/cells9051300. (2020)
Zheng Y, Buchwalter RA, Zheng C, Wight EM, Chen JV, Megraw TL
A perinuclear microtubule-organizing centre controls nuclear positioning and basement membrane secretion.
Nature Cell Biology. doi: 10.1038/s41556-020-0470-7 (2020). See BioRxiv preprint for extended version.
Zheng Y, Mennella V, Marks S, Wildonger J, Elnagdi E, Agard D, Megraw T.L.
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.
Molecular Biology of the Cell. 2016 .
Chen, J. V., Kao, L.R., Jana, S.C., Sivan-Loukianova, E., Mendonça, S., Cabrera, O.A., Singh, P., Cabernard, C., Eberl, D.F., Bettencourt-Dias, M., and Megraw, T. L. (2015).
Rootletin organizes the ciliary rootlet to achieve neuron sensory function in Drosophila.
Journal of Cell Biology
Tozser, J., Earwood, R., Kato, A., Brown, J., Tanaka, K., Didier, R., Megraw, T. L., Blum, M., and Kato, Y. (2015).
TGF-beta Signaling Regulates the Differentiation of Motile Cilia.
Cell reports 11, 1000-1007.
Man, X., Megraw, T. L., and Lim, Y.P. (2015).
Cep68 can be regulated by Nek2 and SCF complex.
European Journal of Cell Biology 94, 162-172.
Bingol, K., Li, D.W., Bruschweiler-Li, L., Cabrera, O.A., Megraw, T., Zhang, F., and Bruschweiler, R. (2015).
Unified and isomer-specific NMR metabolomics database for the accurate analysis of (13)C-(1)H HSQC spectra.
ACS chemical biology 10, 452-459.
Galletta, B.J., Guillen, R.X., Fagerstrom, C.J., Brownlee, C.W., Lerit, D.A., Megraw, T. L., Rogers, G.C., and Rusan, N.M. (2014).
Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies.
Molecular Biology of the Cell 25, 2682-2694.
Chen, J.V., and Megraw, T. L. (2014).
Mother centrioles do a cartwheel to produce just one daughter.
Developmental Cell 30, 111-112.
Chen, J.V., and Megraw, T. L. (2014).
Spermitin: a novel mitochondrial protein in Drosophila spermatids.
PloS ONE 9, e108802.
Riparbelli, M.G., Cabrera, O.A., Callaini, G., and Megraw, T. L. (2013).
Unique properties of Drosophila spermatocyte primary cilia.
Biology Open 2, 1137-1147.
----------This article was featured on the cover
Chen, J.V., and Megraw, T. L. (2013).
Cenexin1 and Odf2: splice variants with diverged cilium functions.
Cell Cycle 12, 869.
Riparbelli, M.G., Callaini, G., and Megraw, T. L. (2012).
Assembly and persistence of primary cilia in dividing Drosophila spermatocytes.
Developmental Cell 23, 425-432.
Kao, L.R. and Megraw, T. L. (2012)
Cytokinesis: RhoGEF controls a developmental cleavage switch.
Curr Biol 22: 916-17.
Gopalakrishnan, J., Mennella, V., Blachon, S., Zhai, B., Smith, A. H., Megraw, T. L., Nicastro, D., Gygi, S. P., Agard, D. A., & Avidor-Reiss, T. (2011).
Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome.
Nature communications, 2, 359.
Megraw, T. L., Sharkey, J. T., & Nowakowski, R. S. (2011).
Cdk5rap2 exposes the centrosomal root of microcephaly syndromes.
Trends Cell Biol., 21: 470-480. NIHMS300507
Megraw, T. (2011)
PP2A targets SAS-5 in centriole assembly
Dev Cell, 20: 416-417. Invited commentary. PMC3104853
Barrera, J. A., Kao, L. R., Hammer, R. E., Seemann, J., Fuchs, J. L., & Megraw, T. L. (2010).
CDK5RAP2 regulates centriole engagement and cohesion in mice.
Dev Cell, 18(6), 913-26.
----------This article was featured on the cover
Kao, L. R., & Megraw, T. L. (2009).
Centrocortin cooperates with centrosomin to organize Drosophila embryonic cleavage furrows.
Current Biology, 19(11), 937-42.
Mottier-Pavie, V., & Megraw, T. L. (2009).
Drosophila bld10 is a centriolar protein that regulates centriole, basal body, and motile cilium assembly.
Mol Biol Cell, 20(10), 2605-14.
----------This article was featured on the cover
Kotadia, S., Kao, L. R., Comerford, S. A., Jones, R. T., Hammer, R. E., & Megraw, T. L. (2008).
PP2A-dependent disruption of centrosome replication and cytoskeleton organization in Drosophila by SV40 small tumor antigen.
Oncogene, 27(49), 6334-46.
Zhang, J. and Megraw, T. L. (2007)
Motif 1 of Centrosomin recruits gamma-Tubulin and D-TACC/Msps to embryonic Drosophila centrosomes.
Mol Biol Cell, 18, 4037-49. PMC1995719
Professor
Member, Center for Brain Repair
Member, Neuroscience Program
Postdoc, Molecular Genetics, Indiana University and the Howard Hughes Medical Institute
PhD, Biochemistry, The University of North Carolina at Chapel Hill
BS, Biochemistry, The State University of New York at Stony Brook
Director, Postdoctoral Career Development Program
Faculty Recruitment committee
Graduate committee
Postdoc Training committee
Life Sciences Symposium steering committee
Proteomics users committee
Innovator Award, Florida State University (2011).
Outstanding Senior Faculty Researcher, Florida State University (2012)
American Society for Cell Biology
Genetics Society of America
European Molecular Biology Organisation
Bioregulation
Modeling Human Disease
Foundations of Medicine 2
Integrated Clinical Sciences
Biomedical Techniques
Professional Development (Tools of the Trade)
Current Research in Biomedical Sciences (BMS4932)
--To see lab web page click HERE--
Research Interests: Centrosomes, cilia, stem cells, asymmetric cell division, neurodegeneration.
Centrosome function in cell division, development and disease
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 basis of MCPH: a neural stem cell disease.
We are investigating a group of 13 proteins whose genes are mutated in a syndrome called autosomal recessive primary microcephaly (MCPH). Mutations result in severe reduction of the cerebral cortex during embryonic development. We are investigating a new line of evidence that points to the mechanism for this disease.
• Metabolic control.
We are investigating a novel function for centrosome proteins in the control of metabolism. The metabolic regulation controlled by centrosome proteins is essential for neuronal function and survival, especially in the face of particular stresses.
• Conversion of mitochondria to MTOCs.
We discovered an alternative splice product of a centrosome protein that targets to the mitochondria. This protein assembles microtubule-organizing centers on the surface of mitochondria. This is a very novel non-centrosomal MTOC, and represents the first molecular characterization of mitochondrial MTOCs.
• Asymmetric centrosomal control of neural stem cell division.
In neural stem cells, we discovered an asymmetric centriole protein that localizes only to the younger daughter centrosome, and is inherited by the renewed stem cell at each division. This protein regulates stem cell polarity.
• Regulation of centriole duplication.
We are investigating a complex of proteins, including centrosomin, that regulate the 'licensing step' that governs centriole duplication during the cell cycle.
Complete list: https://www.ncbi.nlm.nih.gov/myncbi/timothy.megraw.1/bibliography/public/
Buchwalter RA Ogden SC, York SB, Sun L, Zheng C, Hammock C, Cheng Y, Chen JV, Cone AS, Meckes DG, Tang H, Megraw TL
Coordination of Zika Virus Infection and Viroplasm Organization by Microtubules and Microtubule-Organizing Centers.
Cells. doi: 10.3390/cells10123335 (2021).
Debec A, Loppin B, Zheng C, Liu X, Megraw TL
The Enigma of Centriole Loss in the 1182-4 Cell Line.
Cells. 9(5): E1300. doi: 10.3390/cells9051300. (2020)
Zheng Y, Buchwalter RA, Zheng C, Wight EM, Chen JV, Megraw TL
A perinuclear microtubule-organizing centre controls nuclear positioning and basement membrane secretion.
Nature Cell Biology. doi: 10.1038/s41556-020-0470-7 (2020). See BioRxiv preprint for extended version.
Zheng Y, Mennella V, Marks S, Wildonger J, Elnagdi E, Agard D, Megraw T.L.
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.
Molecular Biology of the Cell. 2016 .
Chen, J. V., Kao, L.R., Jana, S.C., Sivan-Loukianova, E., Mendonça, S., Cabrera, O.A., Singh, P., Cabernard, C., Eberl, D.F., Bettencourt-Dias, M., and Megraw, T. L. (2015).
Rootletin organizes the ciliary rootlet to achieve neuron sensory function in Drosophila.
Journal of Cell Biology
Tozser, J., Earwood, R., Kato, A., Brown, J., Tanaka, K., Didier, R., Megraw, T. L., Blum, M., and Kato, Y. (2015).
TGF-beta Signaling Regulates the Differentiation of Motile Cilia.
Cell reports 11, 1000-1007.
Man, X., Megraw, T. L., and Lim, Y.P. (2015).
Cep68 can be regulated by Nek2 and SCF complex.
European Journal of Cell Biology 94, 162-172.
Bingol, K., Li, D.W., Bruschweiler-Li, L., Cabrera, O.A., Megraw, T., Zhang, F., and Bruschweiler, R. (2015).
Unified and isomer-specific NMR metabolomics database for the accurate analysis of (13)C-(1)H HSQC spectra.
ACS chemical biology 10, 452-459.
Galletta, B.J., Guillen, R.X., Fagerstrom, C.J., Brownlee, C.W., Lerit, D.A., Megraw, T. L., Rogers, G.C., and Rusan, N.M. (2014).
Drosophila pericentrin requires interaction with calmodulin for its function at centrosomes and neuronal basal bodies but not at sperm basal bodies.
Molecular Biology of the Cell 25, 2682-2694.
Chen, J.V., and Megraw, T. L. (2014).
Mother centrioles do a cartwheel to produce just one daughter.
Developmental Cell 30, 111-112.
Chen, J.V., and Megraw, T. L. (2014).
Spermitin: a novel mitochondrial protein in Drosophila spermatids.
PloS ONE 9, e108802.
Riparbelli, M.G., Cabrera, O.A., Callaini, G., and Megraw, T. L. (2013).
Unique properties of Drosophila spermatocyte primary cilia.
Biology Open 2, 1137-1147.
----------This article was featured on the cover
Chen, J.V., and Megraw, T. L. (2013).
Cenexin1 and Odf2: splice variants with diverged cilium functions.
Cell Cycle 12, 869.
Riparbelli, M.G., Callaini, G., and Megraw, T. L. (2012).
Assembly and persistence of primary cilia in dividing Drosophila spermatocytes.
Developmental Cell 23, 425-432.
Kao, L.R. and Megraw, T. L. (2012)
Cytokinesis: RhoGEF controls a developmental cleavage switch.
Curr Biol 22: 916-17.
Gopalakrishnan, J., Mennella, V., Blachon, S., Zhai, B., Smith, A. H., Megraw, T. L., Nicastro, D., Gygi, S. P., Agard, D. A., & Avidor-Reiss, T. (2011).
Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome.
Nature communications, 2, 359.
Megraw, T. L., Sharkey, J. T., & Nowakowski, R. S. (2011).
Cdk5rap2 exposes the centrosomal root of microcephaly syndromes.
Trends Cell Biol., 21: 470-480. NIHMS300507
Megraw, T. (2011)
PP2A targets SAS-5 in centriole assembly
Dev Cell, 20: 416-417. Invited commentary. PMC3104853
Barrera, J. A., Kao, L. R., Hammer, R. E., Seemann, J., Fuchs, J. L., & Megraw, T. L. (2010).
CDK5RAP2 regulates centriole engagement and cohesion in mice.
Dev Cell, 18(6), 913-26.
----------This article was featured on the cover
Kao, L. R., & Megraw, T. L. (2009).
Centrocortin cooperates with centrosomin to organize Drosophila embryonic cleavage furrows.
Current Biology, 19(11), 937-42.
Mottier-Pavie, V., & Megraw, T. L. (2009).
Drosophila bld10 is a centriolar protein that regulates centriole, basal body, and motile cilium assembly.
Mol Biol Cell, 20(10), 2605-14.
----------This article was featured on the cover
Kotadia, S., Kao, L. R., Comerford, S. A., Jones, R. T., Hammer, R. E., & Megraw, T. L. (2008).
PP2A-dependent disruption of centrosome replication and cytoskeleton organization in Drosophila by SV40 small tumor antigen.
Oncogene, 27(49), 6334-46.
Zhang, J. and Megraw, T. L. (2007)
Motif 1 of Centrosomin recruits gamma-Tubulin and D-TACC/Msps to embryonic Drosophila centrosomes.
Mol Biol Cell, 18, 4037-49. PMC1995719