William A. Mohler, PhDAssociate Professor, Genetics and Genome Sciences
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Degree | Institution | Major |
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AB | Harvard College | Biochemical Sciences |
PhD | Stanford University | Pharmacology |
Post-Graduate Training
Training | Institution | Specialty |
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Visiting Graduate Student | National Institutes of Health | Laboratory of Bruce Paterson, Ph.D. |
Professional Training | Marine Biological Laboratory | Summer course-Physiology: Cellular and Molecular Biology |
Fellowship | University of Wisconsin | Laboratory of John G. White, Ph.D., Laboratory of Molecular Biology |
Awards
Name of Award/Honor | Awarding Organization |
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Osborn Graduate Teaching Award: first recipient, chosen by ballot | graduate students in Biomedical Sciences |
Cum Laude in Field of Biomedical Sciences | Harvard College, Cambrdige, MA |
Name & Description | Category | Role | Type | Scope | Start Year | End Year |
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Intl. C. elegans Meeting | Other | Workshop Organizer | External | International | 2011 | |
Qualifying exam committee for UCHC Cell Analysis and Modeling PhD student Akeisha Belgrave. | Advisory Committee | Committee member | UConn Health | University | 2011 | |
Gordon Research Conference on Cell-Cell Fusion | Other | Chair | External | National | 2009 | |
Gordon Research Conference on Cell-Cell Fusion | Other | Vice Chair | External | National | 2007 | |
Graduate Programs Committee | Education Committee | Full member, area of concentration director | UConn Health | Local | 2006 | 2012 |
Organizing Committee, C.elegans Early Embryo Mtg. | Other | Committee member | External | National | 2006 | |
Qualifying exam committee for UCHC Cell Biology PhD student Rachael Norris. | Advisory Committee | Committee member | UConn Health | University | 2006 | |
poster competition at 15th International C. elegans Meeting | Other | Judge | External | International | 2005 | |
Graduate Programs Committee | Advisory Committee | Member | UConn Health | University | 2005 | |
Genetics and Developmental Biology area of conc. | Advisory Committee | Associate Director | UConn Health | University | 2005 | 2006 |
CCAM Biophotonics faculty search committee | Advisory Committee | Member | UConn Health | University | 2005 | 2006 |
UCHC Biomedical Sciences graduate admissions committee | Education Committee | Member | UConn Health | University | 2004 | 2006 |
MSTP training grant site visit | Advisory Committee | faculty participant | UConn Health | University | 2004 | |
Dental Council | Advisory Committee | Memeber | UConn Health | University | 2003 | 2006 |
Genetics and Developmental Biology faculty search committee | Advisory Committee | Member | UConn Health | University | 2003 | 2004 |
Qualifying exam committee for UCHC Developmental Biology PhD student Stephan Goupil. | Advisory Committee | Committee member | UConn Health | University | 2003 | |
Genetics and Developmental Biology graduate program | Education Committee | Curriculum Director | UConn Health | University | 2002 | 2005 |
GPC curriculum committee, UCHC | Editorial Board | Member | UConn Health | University | 2002 | 2006 |
Office of Educational Assessment, coordinating implementation of the Blackboard Survey system for graduate course evaluations | Advisory Committee | Graduate faculty liaison | UConn Health | University | 2002 | 2006 |
GMBB program annual retreat planning committee. | Advisory Committee | Member | UConn Health | University | 2002 | |
Qualifying exam committee for UCHC Developmental Biology PhD student Brianna Solod and UCHC GMBB PhD student Theresa Santiago. | Advisory Committee | Committee member | UConn Health | University | 2002 | |
Summer undergraduate research program admissions committee | Education Committee | Member | UConn Health | University | 2001 | 2003 |
Qualifying exam committee for UCHC Developmental Biology PhD student Dana Philipps. | Advisory Committee | Committee member | UConn Health | University | 2001 | |
American Society for Cell Biology | Professional/Scientific Organization | Member | External | National | ||
Biophysical Society | Professional/Scientific Organization | Member | External | National | ||
Biophysical Journal | Professional/Scientific Journal | Reviewer | External | National | ||
Journal of Biomedical Optics | Professional/Scientific Journal | Reviewer | External | National | ||
Genome Informatics | Professional/Scientific Journal | Reviewer | External | National | ||
Indian Academy of Sciences | Professional/Scientific Journal | Reviewer | External | National | ||
Nature Biotechnology | Professional/Scientific Journal | Reviewer | External | National | ||
Nature Cell Biology | Professional/Scientific Journal | Reviewer | External | National | ||
Development | Professional/Scientific Journal | Reviewer | External | National | ||
Source Code for Biology | Professional/Scientific Journal | Reviewer | External | National | ||
PLoSONE | Professional/Scientific Journal | Reviewer | External | National | ||
NCRR special review panel for shared instrumentation grant applications | Advisory Committee | Grant reviewer | External | National | ||
Yale Comprehensive Cancer Center Gilman Foundation Program | Advisory Committee | Grant reviewer | External | University | ||
ARRA-GO special review panel | Advisory Committee | Grant reviewer | External | National |
We are pursuing three projects that extend from our interests in the development of tissues and the innovative application of light microscopy to biology: Developmental cell fusion, Second-harmonic generation microscopy, and Genome-wide imaging of C. elegans development. Developmental Cell Fusion Formation of multinucleate syncytia (giant cells) is essential to the development and regeneration of human skeletal muscle, and is key to fertilization and the formation of various specialized cell types in many species. Yet the mechanism by which fusing cells recognize each other and merge their membranes is poorly understood. We use genetics and microscopy in the nematode worm C. elegans to study the mechanisms by which cells fuse during this animal's development. Our recent studies of the unique cell-fusion protein EFF-1 indicate that the molecular machinery of cell fusion has been re-invented during evolution of different cell types and divergent organisms. We are also investigating the mechanism of mammalian myoblast fusion, combining experimental tools developed specifically for that system with our experience from the study of C. elegans syncytia. Second-harmonic Generation (SHG) imaging We recently discovered that thick myosin filaments in the actomyosin lattice of striated muscle cells produce second-harmonic generation. This non-linear optical effect produces bright contrast from the endogenous unlabeled proteins themselves. The second harmonic light can be imaged at high three-dimensional spatial resolution on a microscope, yielding a digital profile of the arrangement and internal structure of muscle fibers in live tissue. We are applying SHG microscopy to the study of degenerative muscle diseases and aging, as well as the process of myofibrillogenesis in the differentiation of muscle cells. Genome-wide Imaging of C. Elegans Development We are working to develop a database of genome and proteome activity in the developing nematode C. elegans. This tiny yet complex animal is remarkable both for its transparency and the cell-by-cell invariance its developmental program. We plan to use two distinct fluorescence imaging technologies to record the dynamics of expression and localization of GFP-tagged gene products within live worms and embryos. The standardized digital data produced by these instruments will then be correlated to find genes and proteins that work coordinately in the formation of specific cell types and tissues.
Not accepting students for Lab Rotationsat this time.
Journal Articles
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Differential adhesion regulates neurite placement via a retrograde zippering mechanism.
eLife 2021 Nov;10
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Structural and developmental principles of neuropil assembly in C. elegans.
Nature 2021 Mar;591(7848):99-104
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Rapid image deconvolution and multiview fusion for optical microscopy.
Nature biotechnology 2020 Jun;38(11):1337-1346
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Isotropic Light-Sheet Microscopy and Automated Cell Lineage Analyses to Catalogue Caenorhabditis elegans Embryogenesis with Subcellular Resolution.
Journal of visualized experiments : JoVE 2019 Jun;(148):
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The EFF-1A Cytoplasmic Domain Influences Hypodermal Cell Fusions in C. elegans But Is Not Dependent on 14-3-3 Proteins.
PloS one 2016 Jan;11(1):e0146874
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Untwisting the Caenorhabditis elegans embryo.
eLife 2015 Dec;4
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WormGUIDES: an interactive single cell developmental atlas and tool for collaborative multidimensional data exploration.
BMC bioinformatics 2015 Jan;16189
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Caenorhabditis elegans as a platform to study the mechanism of action of synthetic antitumor lipids.
Cell cycle (Georgetown, Tex.) 2014 Nov;13(21):3375-89
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UNC-40/DCC, SAX-3/Robo, and VAB-1/Eph polarize F-actin during embryonic morphogenesis by regulating the WAVE/SCAR actin nucleation complex.
PLoS genetics 2012 Aug;8(8):e1002863
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Stoichiometry of Nck-dependent actin polymerization in living cells.
The Journal of cell biology 2012 May;197(5):643-58
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The branched actin nucleator Arp2/3 promotes nuclear migrations and cell polarity in the C. elegans zygote.
Developmental biology 2011 Sep;357(2):356-69
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New insights into the mechanisms and roles of cell-cell fusion.
International review of cell and molecular biology 2011 Jan;289149-209
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α-Catulin CTN-1 is required for BK channel subcellular localization in C. elegans body-wall muscle cells.
The EMBO journal 2010 Sep;29(18):3184-95
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Imaging embryonic development in Caenorhabditis elegans.
Cold Spring Harbor protocols 2010 Mar;2010(3):pdb.top71
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Suspended embryo mount for imaging Caenorhabditis elegans.
Cold Spring Harbor protocols 2010 Mar;2010(3):pdb.prot5388
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Dynamics of peptidergic secretory granule transport are regulated by neuronal stimulation.
BMC neuroscience 2010 Jan;1132
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Google 'EarthWorm'.
Nature methods 2009 Sep;6(9):635-6
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The WAVE/SCAR complex promotes polarized cell movements and actin enrichment in epithelia during C. elegans embryogenesis.
Developmental biology 2008 Dec;324(2):297-309
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Depolymerization-driven flow in nematode spermatozoa relates crawling speed to size and shape.
Biophysical journal 2008 May;94(10):3810-23
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Measurement of muscle disease by quantitative second-harmonic generation imaging.
Journal of biomedical optics 2008 Jan;13(4):044018
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Optical imaging of cell fusion and fusion proteins in Caenorhabditis elegans.
Methods in molecular biology (Clifton, N.J.) 2008 Jan;475223-44
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Quantitative assays for cell fusion.
Methods in molecular biology (Clifton, N.J.) 2008 Jan;475347-61
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Ultrastructural imaging of cell fusion in Caenorhabditis elegans.
Methods in molecular biology (Clifton, N.J.) 2008 Jan;475245-62
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Genome-scale analysis of in vivo spatiotemporal promoter activity in Caenorhabditis elegans.
Nature biotechnology 2007 Jun;25(6):663-8
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Coherent and incoherent SHG in fibrillar cellulose matrices.
Optics express 2007 Mar;15(6):3348-60
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Chapter 7 Second harmonic generation imaging microscopy of fibrillar structures
Handai Nanophotonics 2007 Jan;3115-130
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Second harmonic generation imaging microscopy studies of osteogenesis imperfecta.
Journal of biomedical optics 2007 Jan;12(5):051805
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Minimotif Miner: a tool for investigating protein function.
Nature methods 2006 Mar;3(3):175-7
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Characterization of the myosin-based source for second-harmonic generation from muscle sarcomeres.
Biophysical journal 2006 Jan;90(2):693-703
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Optical clearing for improved contrast in second harmonic generation imaging of skeletal muscle.
Biophysical journal 2006 Jan;90(1):328-39
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C-terminal mutants of C. elegans Smads reveal tissue-specific requirements for protein activation by TGF-beta signaling.
Development (Cambridge, England) 2005 Aug;132(15):3505-13
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Fusogenic activity of EFF-1 is regulated via dynamic localization in fusing somatic cells of C. elegans.
Current biology : CB 2005 Mar;15(5):413-23
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Annexin I is an endogenous ligand that mediates apoptotic cell engulfment.
Developmental cell 2003 Apr;4(4):587-98
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A novel engulfment ligand from apoptotic cells identified by quantitative proteomics
Developmental Cell 2003 Jan;4(4):587-598
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Nonlinear Optical Spectroscopy: And Imaging of Structural Proteins in Living Tissues
Optics and Photonics News 2003 Jan;14(6):40-45
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Second harmonic generation imaging of endogenous structural proteins.
Methods (San Diego, Calif.) 2003 Jan;29(1):97-109
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Second harmonic imaging microscopy.
Methods in enzymology 2003 Jan;36147-69
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Analysis of multidimensional biological image data.
BioTechniques 2002 Dec;33(6):1268-73
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The type I membrane protein EFF-1 is essential for developmental cell fusion.
Developmental cell 2002 Mar;2(3):355-62
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Three-dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues.
Biophysical journal 2002 Jan;82(1 Pt 1):493-508
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The zinc finger protein DIE-1 is required for late events during epithelial cell rearrangement in C. elegans.
Developmental biology 2001 Aug;236(1):165-80
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Second-harmonic imaging microscopy of living cells.
Journal of biomedical optics 2001 Jul;6(3):277-86
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Completion of cytokinesis in C. elegans requires a brefeldin A-sensitive membrane accumulation at the cleavage furrow apex.
Current biology : CB 2001 May;11(10):735-46
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The Caenorhabditis elegans APC-related gene apr-1 is required for epithelial cell migration and Hox gene expression.
Genes & development 2000 Apr;14(7):874-86
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Neural cell adhesion molecule (NCAM) and myoblast fusion
Developmental Biology 2000 Jan;221(1):112-119
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Visual reality: using computer reconstruction and animation to magnify the microscopist's perception.
Molecular biology of the cell 1999 Oct;10(10):3061-5
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Multiphoton laser scanning microscopy for four-dimensional analysis of Caenorhabditis elegans embryonic development.
Optics express 1998 Oct;3(9):325-31
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Dynamics and ultrastructure of developmental cell fusions in the Caenorhabditis elegans hypodermis.
Current biology : CB 1998 Sep;8(19):1087-90
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Stereo-4-D reconstruction and animation from living fluorescent specimens.
BioTechniques 1998 Jun;24(6):1006-10, 1012
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Fusion competence of myoblasts rendered genetically null for N-cadherin in culture.
The Journal of cell biology 1997 Jul;138(2):331-6
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Rapid plasmid minipreps in microplate format from culture to gel.
BioTechniques 1997 Mar;22(3):388-90
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Genetic analysis of alpha 4 integrin functions in the development of mouse skeletal muscle.
The Journal of cell biology 1996 Nov;135(3):829-35
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Gene expression and cell fusion analyzed by lacZ complementation in mammalian cells.
Proceedings of the National Academy of Sciences of the United States of America 1996 Oct;93(22):12423-7
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Spectrophotometric quantitation of tissue culture cell number in any medium.
BioTechniques 1996 Aug;21(2):260-2, 264, 266
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Membrane-bound neomycin phosphotransferase confers drug-resistance in mammalian cells: a marker for high-efficiency targeting of genes encoding secreted and cell-surface proteins.
Somatic cell and molecular genetics 1994 May;20(3):153-62
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Molecular cloning of mevalonate kinase and regulation of its mRNA levels in rat liver.
Proceedings of the National Academy of Sciences of the United States of America 1990 Apr;87(8):2872-6
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Nucleotide sequence of the rat low density lipoprotein receptor cDNA.
Nucleic acids research 1989 Feb;17(3):1259-60
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Book Chapters
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Cell-cell fusion: transient channels leading to plasma membrane merger
Cell-Cell Channels 2006 Jan;
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Imaging Embryonic Development in Caenorhabditis elegans
Imaging in Neuroscience and Development 2005 Jan;
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Multiphoton imaging of embryonic development
Imaging Neurons: A Laboratory Manual 2000 Jan;
Conference Papers
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Automated extraction of cell lineages and spatial migration paths in live C. elegans embryos from 4D fluorescence microscopy image sequences
Microscopy and Microanalysis 2006 Jan;12(SUPPL. 2):1672-1673
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Second harmonic generation imaging of skeletal muscle tissue and myofibrils
Proceedings of SPIE - The International Society for Optical Engineering 2006 Jan;6089
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A novel quantitative morphometry approach to assess regeneration in dystrophic skeletal muscle.
Neuromuscular disorders : NMD 2004 Jan;24(7):596-603
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Second Harmonic Generation Imaging of Endogenous Structural Proteins
Proceedings of SPIE - The International Society for Optical Engineering 2003 Jan;496373-80
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Second harmonic imaging microscopy
Microscopy and Microanalysis 2003 Jan;9(SUPPL. 2):170-171
Dissertations
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Analysis of Mouse Myoblast Fusion.
Doctoral dissertation, Stanford University Department of Pharmacology. 1997 Jan;
Short Surveys
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Cell-cell fusion.
FEBS letters 2007 May;581(11):2181-93
Websites
Title or Abstract | Type | Sponsor/Event | Date/Year | Location |
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Dynamics at an EFF-1-dependent Fusion Synapse | Talk | Gordon Research Conference on Cell-Cell Fusion | 2011 | Biddeford, ME |
The GLOWorm repository & GLOWormJ: a system for distribution and analysis of multidimensional embryological images. | Talk | International C. elegans Meeting | 2011 | Los Angeles, CA |
Realizing the potential of image data from C. elegans. | Talk | Boston Area Worm Meeting | 2010 | Cambridge, MA. |
Toward a GLOWorm database/software/interface. | Talk | New York Area Worm Meeting | 2010 | New York, NY |
Chair’s introduction, and discussion leader introduction to cell fusion in epithelia. | Talk | Gordon Research Conference on Cell-Cell Fusion | 2009 | New London, NH |
Appreciating massive datasets from tiny specimens; focus on cell tracking in confocal recordings. | Talk | Yale Advanced Microscopy Workshop | 2009 | New Haven, CT |
Chair’s introduction, and discussion leader introduction to cell fusion in epithelia. | Panel Discussion | Gordon Research Conference on Cell-Cell Fusion | 2009 | New London, NH |
The challenges and benefits of high-resolution imaging of intact specimens. | Talk | E. E. Just Symposium | 2008 | Howard University, Washington, DC. |
Wisdom from worms about fusing cell, fusing photons, y farmacologia. | Talk | Centro de Investigación del Cancer | 2008 | Universidad de Salamanca, Spain |
Application of TCNP technologies to understand polarity in cell-cell fusion. | Talk | Technology Centers for Networks and Pathways, All-Hands Meeting | 2008 | Bethesda, MD |
Dynamic regulation and localization of EFF-1 in fusing cells of C. elegans. | Talk | Gordon Research Conference on Cell-Cell Fusion | 2007 | New London, NH |
Multiple examples of multidimensional imaging. | Talk | Connecticut Microscopy Society | 2007 | Yale University, New Haven, CT |
Diagnostic quantification of muscle contractile structure by second-harmonic generation (SHG) imaging. | Talk | Advanced Optical Methods Workshop | 2007 | Berkeley, CA. |
Making giant cells: Somatic cell fusion in C. elegans development. | Talk | UMDNJ | 2006 | Piscataway, New Jersey |
Applying second-harmonic generation imaging to the study of neuromuscular disease and aging. | Talk | Mayo Alzheimer’s Disease/Parkinson’s Disease Seminar Series | 2006 | Mayo Clinic, Jacksonville, Florida |
Regulation and trafficking of of EFF-1 in cell fusion. | Talk | C. elegans topic meeting | 2006 | Madison, WI |
Developmental cell fusion: dynamic regulation of the prototype fusogen, EFF-1. | Talk | Program in Molecular and Cellular Biology | 2005 | UMass, Amherst, Massachusetts |
Developmental cell fusion: lessons from the "prototype" fusogen, EFF-1. | Talk | Center for Cellular and Molecular Biology | 2005 | Hyderabad, India |
Quantifying sarcopenic changes in aging muscle by second-harmonic generation imaging. | Talk | Ellison Medical Foundation Colloquium on the Biology of Aging | 2005 | Woods Hole, MA. |
Nonlinear optics and multidimensional imaging of developing tissues. | Talk | Society for Developmental Biology | 2005 | San Francisco, CA |
GLOWorm peep-show: a preliminary collection of interactive movies of embryonic gene-expression. | Poster | Fifteenth International C. elegans Meeting | 2005 | Los Angeles, CA |
Keynote lecture presented: Second-harmonic generation imaging of endogenous tissue structures. | Talk | Frontiers in Biomechanics (US Natl. Cmte. on Biomechanics), | 2005 | Vail, Colorado |
Appreciating massive datasets from tiny specimens. | Talk | Zeiss-CCMB Microscopy Workshop | 2005 | Hyderabad, India |
Second-harmonic generation (SHG) microscopy in live cells and tissues. | Talk | Zeiss-CCMB Microscopy Workshop | 2005 | Hyderabad, India |
Function of EFF-1 in C. elegans cell fusion. | Poster | American Society for Cell Biology | 2004 | Washington, DC. |
Genome-wide imaging of C. elegans embryogenesis. | Talk | ORFeome meeting | 2004 | Boston, MA |
A single-protein fusogen in the somatic cells of C. elegans. | Poster | Northeast Society for Developmental Biology | 2004 | Woods Hole, MA |
Lessons from a worm about fusing cells and fusing photons. | Talk | Center for Regenerative Biology | 2003 | UConn, Storrs, Connecticut |
Function of EFF-1 in C. elegans cell fusion. | Poster | American Society for Cell Biology | 2003 | San Francisco, CA |
Genome-wide imaging of C. elegans development. | Talk | ORFeome meeting | 2003 | Boston, MA |
Analyzing GFP expression patterns throughout C. elegans development. | Talk | Current Topics in Gene Expression and Proteomics, 6th meeting | 2003 | San Diego |
Imaging strategies and data types for genome-wide comparison and pattern-matching of GFP expression patterns: GLO-Worm. | Talk | Fourteenth International C. elegans Meeting | 2003 | Los Angeles |
Second harmonic imaging of endogenous protein structures. | Talk | Symposium on Biological Imaging | 2003 | Madison, WI |
Mechanism of developmental cell fusion in C. elegans. | Talk | Dept. of Biology, CUNY Queens College | 2002 | New York |
Lessons from a worm about fusing cells and fusing photons. | Talk | Marine Biological Laboratory | 2002 | Woods Hole, Massachusetts |
Characterizing EFF-1 function in C. elegans cell fusion. | Poster | American Society for Cell Biology | 2002 | San Francisco |
Second harmonic generation imaging of muscle contractile apparatus in live tissue. | Poster | American Society for Cell Biology | 2002 | San Francisco |
Post-embryonic Developmental Expression Chronograms: a new functional genomics data type generated using a nematode fluorescence sorting system. | Talk | East Coast Worm Meeting | 2002 | Durham, NH |
Multidimensional imaging of C. elegans development. | Talk | ORFeome meeting | 2002 | Boston |
C. elegans development. | Talk | Microscopy and Microanalysis 2001 | 2001 | Long Beach, CA |
Appreciating massive data sets from tiny specimens. | Talk | Microscopy and Microanalysis 2001 | 2001 | Long Beach, CA |
eff-1 is required for cell fusion in epithelial syncytia. | Talk | Thirteenth International C. elegans Meeting | 2001 | Los Angeles |
New methods for imaging endogenous protein structures in live cells and tissues: high-resolution second-harmonic and dual-mode non-linear microscopy. | Talk | Thirteenth International C. elegans Meeting | 2001 | Los Angeles |
Cellular and molecular mechanism of cell fusion in C. elegans. | Talk | Department of Cell Biology, Yale University Medical School | 2000 | New Haven, Connecticut |
C. elegans embryogenesis viewed by multiphoton microscopy and 4D/5D computer animation.. | Talk | Gordon Research Conference: Developmental Physiology | 2000 | Plymouth, NH |
A C. elegans. Mutation Blocking Epidermal Cell Fusions. | Poster | American Society for Cell Biology | 1999 | Washington, D.C. |
Microscopy and Cell Biology. | Talk | Cold Spring Harbor Laboratory C. elegans course | 1999 | Cold Spring Harbor |
Visual reality: magnifying the microscopist's perception. | Talk | Imaging Across Scientific Boundaries, Dartmouth College Symp | 1999 | Hanover, NH |
Hypodermal cell fusions are not required for gross morphogenesis in C. elegans. | Poster | Twelfth International C. elegans Meeting | 1999 | Madison, Wisconsin |
Mechanisms of Membrane Fusion and Resealing. | Talk | American Society for Cell Biology | 1998 | San Francisco |
Multiphoton Fluorescence Microscopy for Dynamic Observation of Cell Fusion In C. elegans Embryos. | Talk | Biophysical Society, 42nd Annual Meeting | 1998 | Kansas City, Missouri |
4D Timelapse Imaging of Embryonic Lineage and Morphogenesis using a Vital Membrane Dye and Multiple-Photon Fluorescence Microscopy. | Talk | Eleventh International C. elegans Meeting | 1997 | Madison, Wisconsin |