Author
Gregory J. Pazour
Other affiliations: National Institutes of Health, Worcester Foundation for Biomedical Research, University of Minnesota ...read more
Bio: Gregory J. Pazour is an academic researcher from University of Massachusetts Medical School. The author has contributed to research in topics: Cilium & Intraflagellar transport. The author has an hindex of 64, co-authored 142 publications receiving 25151 citations. Previous affiliations of Gregory J. Pazour include National Institutes of Health & Worcester Foundation for Biomedical Research.
Topics: Cilium, Intraflagellar transport, Flagellum, Dynein, Ciliogenesis
Papers published on a yearly basis
Papers
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TL;DR: It is found that intraflagellar transport 20 mediates the ability of Ror2 signaling to induce the invasiveness of tumors that lack primary cilia, and IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex.
Abstract: Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
13,354 citations
University of Washington1, University of Wisconsin–Milwaukee2, École Normale Supérieure3, University of British Columbia4, University of Wisconsin-Madison5, Princeton University6, Martek Biosciences Corporation7, University of California, Santa Barbara8, University of Melbourne9, University of California, San Diego10, Sandia National Laboratories11, University of California, Santa Cruz12, University of Regensburg13, Oak Ridge National Laboratory14, University of Hull15, Joint Genome Institute16, Academy of Sciences of the Czech Republic17, University of Massachusetts Medical School18, Woods Hole Oceanographic Institution19, Alfred Wegener Institute for Polar and Marine Research20, San Francisco State University21, University of California, Berkeley22
TL;DR: The 34 million-base-pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand base-pair mitochondrial genomes were reported in this article.
Abstract: Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for approximately 20% of global carbon fixation. We report the 34 million-base pair draft nuclear genome of the marine diatom Thalassiosira pseudonana and its 129 thousand-base pair plastid and 44 thousand-base pair mitochondrial genomes. Sequence and optical restriction mapping revealed 24 diploid nuclear chromosomes. We identified novel genes for silicic acid transport and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic enzymes for several types of polyunsaturated fatty acids, use of a range of nitrogenous compounds, and a complete urea cycle, all attributes that allow diatoms to prosper in aquatic environments.
1,945 citations
TL;DR: The primary cilia in the kidney of Tg737 mutant mice are shorter than normal, indicating that IFT is important forPrimary cilia assembly in mammals and that defects in their assembly can lead to polycystic kidney disease.
Abstract: Intraflagellar transport (IFT) is a rapid movement of multi-subunit protein particles along flagellar microtubules and is required for assembly and maintenance of eukaryotic flagella. We cloned and sequenced a Chlamydomonas cDNA encoding the IFT88 subunit of the IFT particle and identified a Chlamydomonas insertional mutant that is missing this gene. The phenotype of this mutant is normal except for the complete absence of flagella. IFT88 is homologous to mouse and human genes called Tg737. Mice with defects in Tg737 die shortly after birth from polycystic kidney disease. We show that the primary cilia in the kidney of Tg737 mutant mice are shorter than normal. This indicates that IFT is important for primary cilia assembly in mammals. It is likely that primary cilia have an important function in the kidney and that defects in their assembly can lead to polycystic kidney disease.
1,081 citations
TL;DR: This paper used mass spectrometry to identify proteins in purified flagella from the green alga Chlamydomonas reinhardtii and found that flagellum is rich in motor and signal transduction components, and contains numerous proteins with homologues associated with diseases such as cystic kidney disease, male sterility, and hydrocephalus in humans and model vertebrates.
Abstract: Cilia and flagella are widespread cell organelles that have been highly conserved throughout evolution and play important roles in motility, sensory perception, and the life cycles of eukaryotes ranging from protists to humans. Despite the ubiquity and importance of these organelles, their composition is not well known. Here we use mass spectrometry to identify proteins in purified flagella from the green alga Chlamydomonas reinhardtii. 360 proteins were identified with high confidence, and 292 more with moderate confidence. 97 out of 101 previously known flagellar proteins were found, indicating that this is a very complete dataset. The flagellar proteome is rich in motor and signal transduction components, and contains numerous proteins with homologues associated with diseases such as cystic kidney disease, male sterility, and hydrocephalus in humans and model vertebrates. The flagellum also contains many proteins that are conserved in humans but have not been previously characterized in any organism. The results indicate that flagella are far more complex than previously estimated.
999 citations
University of California, San Diego1, Stanford University2, United States Department of Energy3, Ghent University4, University of Arizona5, University of California, Los Angeles6, Scripps Research Institute7, Centre national de la recherche scientifique8, University of Mainz9, University of Massachusetts Medical School10, J. Craig Venter Institute11, University of Maryland, College Park12
TL;DR: It is speculated that this latter process may be involved in altering the cell-surface characteristics of each species, and selenoenzymes, novel fusion proteins, and loss of some major protein families including ones associated with chromatin are likely important adaptations for achieving a small cell size.
Abstract: The smallest known eukaryotes, at ≈1-μm diameter, are Ostreococcus tauri and related species of marine phytoplankton. The genome of Ostreococcus lucimarinus has been completed and compared with that of O. tauri. This comparison reveals surprising differences across orthologous chromosomes in the two species from highly syntenic chromosomes in most cases to chromosomes with almost no similarity. Species divergence in these phytoplankton is occurring through multiple mechanisms acting differently on different chromosomes and likely including acquisition of new genes through horizontal gene transfer. We speculate that this latter process may be involved in altering the cell-surface characteristics of each species. In addition, the genome of O. lucimarinus provides insights into the unique metal metabolism of these organisms, which are predicted to have a large number of selenocysteine-containing proteins. Selenoenzymes are more catalytically active than similar enzymes lacking selenium, and thus the cell may require less of that protein. As reported here, selenoenzymes, novel fusion proteins, and loss of some major protein families including ones associated with chromatin are likely important adaptations for achieving a small cell size.
612 citations
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28 Jul 2005
TL;DR: PfPMP1）与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
TL;DR: It is found that intraflagellar transport 20 mediates the ability of Ror2 signaling to induce the invasiveness of tumors that lack primary cilia, and IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex.
Abstract: Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
13,354 citations
Icahn School of Medicine at Mount Sinai1, University of Michigan2, Pasteur Institute3, University of California, San Francisco4, European Bioinformatics Institute5, University of California, San Diego6, University of North Carolina at Chapel Hill7, Fred Hutchinson Cancer Research Center8, Gladstone Institutes9, Buck Institute for Research on Aging10
TL;DR: A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
Abstract: A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein–protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19. A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
3,319 citations
University of California, Los Angeles1, United States Department of Energy2, University of Paris3, Duke University4, University of Massachusetts Medical School5, University of California, Berkeley6, Centre national de la recherche scientifique7, University of California, San Francisco8, Sun Yat-sen University9, University of Tennessee Health Science Center10, University of Minnesota11, Iowa State University12, Genetic Information Research Institute13, Salk Institute for Biological Studies14, Stanford University15, University of Liège16, University of Nebraska–Lincoln17, University of Cambridge18, Washington University in St. Louis19, University of Córdoba (Spain)20, Kyoto University21, Carnegie Institution for Science22, National Autonomous University of Mexico23, University of Münster24, École Normale Supérieure25, University of Melbourne26, University of Paris-Sud27, University of Mainz28, Scripps Research Institute29, Ohio State University30, University of Chicago31, University of Jena32, University of Arizona33, Louisiana State University34, University of New Brunswick35, University College London36, University of Potsdam37, Delaware Biotechnology Institute38, Boyce Thompson Institute for Plant Research39, Macquarie University40, Oklahoma State University Center for Health Sciences41, İzmir University of Economics42, Academy of Sciences of the Czech Republic43, Charles University in Prague44, St. Edward's University45, University of Puget Sound46, Hokkaido University47, Tsinghua University48, Washington State University49, Appalachian State University50, Marquette University51
TL;DR: Analyses of the Chlamydomonas genome advance the understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
Abstract: Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the approximately 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
2,554 citations
TL;DR: Advances in nanoparticle design that overcome heterogeneous barriers to delivery are discussed, arguing that intelligent nanoparticles design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.
Abstract: In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers - systemic, microenvironmental and cellular - that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.
2,179 citations