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Lazarowitz, Sondra Gale
Cornell Faculty Member
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Positions
- Professor, Plant Pathology and Plant-Microbe Biology (PPPMB), College of Agriculture and Life Sciences (CALS)
Sondra Lazarowitz, Ph.D., is a Professor in the Department of Plant Pathology at Cornell University, a position she has held since 1998. LazarowitzÕs lab conducts research on how the interactions between viruses and their host plants lead to disease, using several model viruses and the model plant Arabidopsis thaliana. She uses the approaches of molecular genetics, cell biology and genomics to understand how plant viruses use the cellular trafficking machinery to spread from cell-to-cell and invade the host plant. Research in her lab defined, in molecular terms, how geminiviruses move within and between plant cells, and has led to the identification of the first nuclear export signal in a plant protein and to the discovery in plants of a class of proteins, which were thought to only be found in the animal nervous system (synaptotagmins). Lazarowitz has also been active in K-12 science outreach since 1992, having been Program Director of Howard Hughes Medical Institute programs in Undergraduate Biology and Precollege Outreach at Cornell (1999-2004) and the University of Illinois (1992-1998). Lazarowitz, together with George Keiffer and Claudia Washburn, created the Prairie Flowers Program, which has fostered systemic change in middle school science education in rural Illinois. Together with Professor Jerry Uhl at Illinois, she created BioCalc, an innovative introductory calculus course for biology majors at the University of Illinois. Her education and outreach programs have been highlighted in "Beyond Bio 101: The Transformation of Undergraduate Biology Education", the Howard Hughes Medical Institute Bulletin, and on the Discovery Channel. Dr. Lazarowitz holds a Ph.D. in virology and cell biology from The Rockefeller University, and earned a S.B. in life sciences from the Massachusetts Institute of Technology.
Research Areas
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Affiliations
other Cornell affiliations
advisory group member
Research
research overview
- Our overall goal is to identify the molecular and cellular events, which underlie the ability of viruses to infect and spread within a plant to cause disease. Because viruses are obligate intracellular parasites, defining these events can not only lead to the rational development of anti-viral strategies, it also provides insights into how the host regulates gene expression, signal transduction and macromolecular trafficking. For plant viruses, an essential element of their disease potential is their ability to cross the barrier of the plant cell wall to invade the host. Our research has focused on a novel class of proteins encoded by plant viruses: ‘movement proteins’, which play a key role in coordinating replication of the virus genome with its directed transport to and across the plant cell wall. We use the model plant Arabidopsis thaliana and two model plant viruses: the DNA geminivirus Cabbage leaf curl virus (CaLCuV), and the RNA tobamovirus Tobacco mosaic virus (TMV). Employing a variety of approaches –– from molecular and classical genetics to biochemistry, structural biology, confocal imaging, robust transient expression assays and functional genomics –– we have established the current model for how geminivirus movement proteins act to transport the viral genome within and between cells. Our research findings have lead us identify two essential macromolecular transport pathways, which are pirated by plant viruses to transport viral genomes, and to now focus on investigating the role of these trafficking pathways in plant growth and development, as well as in virus movement: (1) The role of vesicle trafficking in plant cell-cell communication; and (2) The regulation of nuclear import and export in plant cells. Why study movement proteins? Plant viruses must cross the barrier of the plant cell wall to move cell-to-cell and invade the host. To do this, they encode unique movement proteins, which are major determinants of virus host range and disease potential. Whereas movement proteins encoded by different viruses can be distinct in their sequences and vary in their specific functions, they ultimately target a common pathway to carry the viral genome across the wall: they alter plasmodesmata (Pd), complex transwall pores that connect adjacent plant cells. Indeed, movement proteins coordinate replication of the viral genome with its directed transport to and across the cell wall to invade the host. They do this by exploiting the cellular machinery for trafficking macromolecules. The final act of crossing the wall is preceded by regulated stages in which movement proteins, with their viral genome cargo, interact with the endomembrane system, the cytoskeleton and, in the case of geminiviruses, the nuclear import and export machinery. This makes them robust models to investigate macromolecular trafficking in plant cells and the regulation of plant cell-cell communication. From geminivirus movement to vesicle trafficking and nuclear shuttling. Our research has established the current model for how the two geminivirus movement proteins, NSP and MP, cooperate to transport the viral single strand DNA genome from its site of replication in the nucleus to, and across, the cell wall (see figure below). NSP (Nuclear Shuttle Protein) acts to import the virus genome into the nucleus for replication, and to export newly replicated virus genomes back to the cytoplasm. MP (cell-to-cell Movement Protein) traps NSP-genome complexes in the cytoplasm and directs these to the cell wall for movement, through what appear to be altered Pd, and into adjacent uninfected cells. NSP then targets the viral genome back to the nucleus to initiate new rounds of infection. Building on this knowledge, we have identified Arabidopsis proteins, which interact with NSP and MP. This has lead us to discover a family of proteins in plants, which regulate vesicle fusion and were thought to only be present in the animal nervous system: synaptotagmins. Our current research is focused on the mechanisms of nuclear shuttling and of vesicle trafficking in plant cells, in terms of how these pathways regulate plant growth and development, and how viruses pirate these pathways to infect the plant and cause disease. The role of vesicle trafficking in plant cell-cell communication. Synaptotagmins (SYTs), are a multigene family thought to be exclusive to animals due to their role in neurotransmitter release. They are calcium (Ca2+) sensors, which are proposed to regulate rapid and synchronous synaptic vesicle exocytosis and endocytosis. What functions do SYTs carry out in plant cells? How are these functions linked to plant virus movement and cell-cell communication via Pd? Answering these questions is one major focus of our lab. There are 5 SYTs (SYT A, B, C, D, E) encoded in Arabidopsis. Genome: SYTA regulates the cell-to-cell trafficking of the distinct movement proteins encoded by CaLCuV (MPCaLCuV) and TMV (MPTMV). Our current studies of SYTA have identified an endosome recycling pathway, which acts to ferry movement proteins and their virus genome cargos to Pd for transport across the cell wall. Our findings also suggest that SYTs play key roles in regulating both the cell-to-cell spread of most, if not all, plant viruses and cell-cell communication in plant development. Questions we are currently addressing include: (1) Does SYTA play a central role in the movement of most, if not all plant viruses? (2) Is it the only SYT with this role? (3) What are the functions of SYTs B, C, D and E in vesicular traffic? (4) Do other SYTs cooperate with SYTA in endosome recycling and/or virus movement? (5) What are the functions of SYTs in plant growth and development? The regulation of nuclear import and export in plant cells. We have visualized the nuclear shuttling of NSP by confocal microscopy, using a transient expression assay in plant protoplasts. These studies established that the mechanism of nuclear shuttling is highly conserved in plants, as well as in animal cells and yeast. NSP is a typical rapidly shuttling nuclear protein, which contains two classic basic nuclear localization signals. It also contains an essential leucine-rich nuclear export sequence, which suggests that it is exported by an exportin 1-type pathway. There are 7 exportin genes, 11 importin α genes, and 11 importin β genes in Arabidopsis. We are currently determining the structure of NSP itself, and bound to DNA, and examining the defective phenotypes in Arabidopsis lines, which are mutated in the importin α and exportin genes. These will provide the basis for our future studies, in which we: (1) identify the specific importin a proteins and exportin(s) that interact with NSP, and examine the structures of these complexes; and (2) in collaboration with investigators at Stony Brook, Ohio State Univ. and the Univ. of Kentucky, use functional genomics to map out the integrated network of pathways that comprise importins, exportins and nuclear pore proteins in Arabidopsis.
research activities
principal investigator on
- SYNAPTOTAGMIN A AND C IN VIRUS MOVEMENT AND PLANT DEVELOPMENT awarded by NATL INST OF HEALTH DHHS 2009 - 2012
- SYNAPTOTAGMIN FUNCTION IN VIRUS MOVEMENT AND PLANT DEVELOPMENT awarded by NATL INST OF HEALTH DHHS 2007 - 2013
area(s) of concentration/expertise
- Bacterial Molecular Genetics & Plant-Microbe Interactions
- Biochemistry and Molecular and Cell Biology
- Cell Biology
- Molecular Basis of Disease Resistance and Susceptibility in Plants
- Molecular genetics, cell-cell signaling in plants
- Plant Biotechnology / Plant Molecular Biology and Genetics
- Plant Cell Biology
- Plant Molecular Biology, Genetics & Cell Biology
- Plant Virology
- Science Education
- Science Education, Science Teacher Education
other area(s) of concentration/expertise
- Animal Virology, virus-host interactions
keywords
- nuclear shuttling
- plant cell-cell communication
- plant virus movement
- synaptotagmins
- vesicle trafficking
- virus-host interactions
submitted impact statement
- Understanding the mechanism of viral spread within plants as a basis for developing disease-resistant crops and improving human nutrition
- High School Connect: Investigative Classroom Modules in Biotechnology and Genomics for New York State Regents and AP students.
- Cornell Howard Hughes program in biology education and K-12 outreach
- Basic research on virus spread in plants leads to the discovery of an endocytic recycling pathway in plants and documents its role in plant virus infection and plant cell-cell communication
- Basic research on virus spread in plants leads to the discovery of an endocytic recycling pathway in plants and documents its role in plant cell-to-cell transport
- Basic research on virus spread identifies a family of proteins that regulate vesicle trafficking and virus infection in plants.
Publications
individual publications
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academic article
- Arabidopsis Synaptotagmin AtSYTA Regulates Early Endosome Formation and Virus Movement Protein Cell-to-Cell Transport. Proceedings of the National Academy of Sciences (PNAS). 107:2491-2496. 2010
- Functional transient genetic transformation of Arabidopsis leaves by biolistic bombardment. Nature Protocols. 4:71-77. 2009
- The geminivirus nuclear shuttle protein NSP inhibits the activity of AtNSI, a vascular-expressed Arabidopsis acetyltransferase regulated with the sink-to-source transition. Plant Physiology. 140:1317-1330. 2006
- Interaction of the movement protein NSP and the Arabidopsis acetyltransferase AtNSI is necessary for cabbage leaf curl geminivirus infection and pathogenicity. Journal of Virology. 78:11161-11171. 2004
- A novel Arabidopsis acetyltransferase interacts with the geminivirus movement protein NSP. Plant Cell. 15:1605-1618. 2003
- The complete sequence of the Arabidopsis and tomato pathogen Pseudomonas syringae pv tomato DC3000. . Proceedings of the National Academy of Sciences (PNAS). 100:10181-10186. 2003
- The complete sequence of the Arabidopsis and tomato pathogen Pseudomonas syringae pv. tomato DC3000. Proceedings at the National Academy of Science USA. 100:10181-10186. 2003
- Genomewide identification of Pseudomonas syringae pv. tomato DC3000 promoters controlled by the HrpL alternative sigma factor.. Proceedings of the National Academy of Sciences (PNAS). 99:2275-2280. 2002
- Nuclear export in plants: Use of geminivirus movement proteins for a cell-based export assay. Plant Cell. 11:1267-1276. 1999
- Probing plant cell structure and function with viral movement proteins. . Current Opinion in Plant Biology. 2:332-338. 1999
- Viral movement proteins as probes for investigating intracellular and intercellular trafficking in plants. . The Plant Cell. 11:535-548. 1999
- Asymmetric infectivity of pseudorecombinants of cabbage leaf curl virus and squash leaf curl virus: Implications for bipartite geminivirus evolution and movement.. Virology. 250:283-292. 1998
- The bipartite geminivirus coat protein aids BR1 function in viral movement by affecting the accumulation of viral single-stranded DNA. . Journal of Virology. 72:9247-9256. 1998
- Plant development from the cellular perspective: Integrating the signals. The Plant Cell. 9:1884-1900. 1997
- The geminivirus BL1 movement protein is associated with endoplasmic reticulum-derived tubules in developing phloem cells. Journal of Virology. 71:3726-3733. 1997
- A viral movement protein as a nuclear shuttle: The geminivirus BR1 movement protein contains domains essential for interaction with BL1 and nuclear localization. Plant Physiology. 110:23-33. 1996
- Getting it together in plant virus movement: Cooperative interactions between bipartite geminivirus movement proteins. . Trends in Cell Biology. 6:353-358. 1996
- Both bipartite geminivirus movement proteins define viral host range, but only BL1 determines viral pathogenicity. Virology. 207:191-204. 1995
- Cooperative interactions in virus movement. The geminivirus BL1 movement protein interacts with BR1 and redirects it from the nucleus to the cell periphery. Plant Cell. 7:1185-1194. 1995
- The geminivirus BR1 movement protein binds single strand nucleic acids and localizes to the nucleus. Plant Cell. 6:995-1006. 1994
- A single missense mutation in the BR1 movement protein alters the host range of the squash leaf curl geminivirus. . Virology. 196:694-702. 1993
- Transgenic tobacco plants expressing the geminivirus BL1 movement protein exhibit viral disease symptoms. . The Plant Cell. 4:795-807. 1993
- Sequence-specific interaction with the viral AL1 protein identifies a geminivirus DNA replication origin. . The Plant Cell. 4:799-809. 1992
- Infectivity and complete nucleotide sequence of the cloned genomic components of SqLCV-E, a bipartite squash leaf curl geminivirus with a broad host range phenotype. . Virology. 180:58-69. 1991
- Molecular characterization of two bipartite geminiviruses causing squash leaf curl disease: Role of replication and movement in determining host range. Virology. 180:70-80. 1991
- Maize streak virus genes essential for systemic spread and symptom development. . EMBO Journal. 8:1023-1032. 1989
- Infectivity and complete nucleotide sequence of a South African isolate of maize streak virus. . Nucleic Acids Research. 16:229-249. 1988
- The molecular characterization of geminiviruses. . The Plant Molecular Biology Reporter. 4:177-192. 1987
- An SV40 mutant with transposed T antigen and VP1 genes. . Journal of Virology. 41:1025-1037. 1982
- Organization of the Epstein-Barr virus DNA molecule: II. Fine mapping of the boundaries of the internal repeat cluster of B95-8 and identification of additional small tandem repeats adjacent to the HR-1 deletion. . Journal of Virology. 43:201-212. 1982
- Monoclonal antibody against a 250,000-dalton glycoprotein of Epstein-Barr virus identifies a membrane antigen and neutralizing antigen. . Proceedings of the National Academy of Sciences (PNAS). 77:2979-2983. 1980
- Initiator regions from the small size class of reovirus messenger RNA protected by rabbit reticulocyte ribosomes. . Journal of Biological Chemistry. 252:7842-7849. 1977
- Enhancement of the infectivity of influenza A and B viruses by proteolytic cleavage of the hemagglutinin polypeptide. . Virology. 68:440-454. 1975
- Proteolytic cleavage by plasmin of the HA polypeptide of influenza virus: Host cell activation of serum plasminogen. Virology. 56:172-180. 1973
- Proteolytic cleavage of the hemagglutinin polypeptide of influenza virus. Function of the uncleaved polypeptide HA. . Virology. 52:199-212. 1973
- Influenza virus structural and nonstructural proteins in infected cells and their plasma membranes. . Virology. 46:830-843. 1971
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booksection
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chapter
- Plant Viruses. Fields' Virology. 641-706. 2007
- Plant Viruses. Fields' Virology. 533-598. 2001
- Constructed mutants of simian virus 40. Plenum Press. 73-92. 1979
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conference paper
- An Arabidopsis protein that mediates nuclear export of Begomovirus genomes. Biology of Plant-Microbe Interactions. 405-409. 2006
- Nuclear shuttling in plant cells. The Nuclear Envelope. 157-176. 2004
- Macromolecular trafficking within and between plant cells as revealed by virus movement proteins. Biology of Plant-Microbe Interactions. 2002
- Intercellular and Intracellular Trafficking: What We Can Learn from Geminivirus Movement. NATO ASI Series: Cellular Integration of Signaling Pathways in Plant Development. 275-288. 1998
- The role of replication and movement functions in the pathogenesis of squash leaf curl virus. Biotechnology and Plant Protection: Viral Pathogenesis and Disease Resistance. 95-114. 1995
- Molecular genetics of maize streak virus. UCLA Symp. on Molecular Biology: Molecular Biology of Plant-Pathogen Interactions. 167-183. 1989
- Studies on proteolytic cleavage and glycosylation of the hemagglutinin of influenza A and B viruses. Negative Strand Viruses. 105-119. 1975
- Plasminogen activators of normal and Rous sarcoma virus-transformed cells. Mechanisms of Virus Disease. 1974
- Structure and assembly of viral membranes. Membrane Research. 163-179. 1972
featured in archived article
speaker at Cornell event
Teaching
teaching overview
- My goals in teaching are to emphasize basic principles and concepts about how viruses interact with their hosts and cause disease, and to convey my enthusiasm for viruses: they are, without doubt, funky, fun and fabulous! As a teacher, my challenges are to make students think about things they never thought about before, and to have student see that they can be doing research. My approach is to focus on principles, and challenge students to understand the experimental evidence for what they read as 'facts', and to think for themselves, integrate information and solve problems. In this way, they can understand anything they may encounter, be it in reading the scientific literature or doing research. There are two principal courses, which I teach. BIOMI 4090/BIOMS (formerly VETMI) 4090 Principles of Virology (3 credits, Fall Semester): This is a unique course, which is designed to convey the basic principles of virus biology, and to illustrate key concepts in virus-host interactions in terms of virus replication and the pathogenesis of disease. This is not a “Virus of the Week” survey course. Rather, the course takes an integrative approach, drawing on examples of animal, plant and bacterial viruses, to focus on unifying principles and the rationale where differences may exist. As a result of this integrative approach, students become well-equipped to read about any virus and understand its replication and pathogenic strategies. BIOPL 4822/PLPA 4822 (formerly 652.1/662.1) Plant Responses to Pathogen Attack (1 credit, Spring Semester even years): This course emphasizes the principle concepts about how plants defend themselves against infection by viruses, bacteria and fungi, and the counterstrategies that these pathogens use to overcome plant defenses. This course was redesigned in Spring 2011 as "Molecular Plant-Microbe Interactions" team taught by myself with A. Collmer, B.G. Turgeon, G. Martin, M. Harrison and S. Winans.
teaching activities
- PLPA-7980: Graduate Teaching Experience - Spring 2013
- PLPA-7990: Graduate-Level Thesis Research - Spring 2013
- PLPA-8900: Master's Level Thesis Research - Spring 2013
- PLPA-9900: Doctoral-Level Thesis Research - Spring 2013
- BIOMI-4090: Principles of Virology - Fall 2012
- BIOMS-4090: Principles of Virology - Fall 2012
- PLPA-4090: Principles of Virology - Fall 2012
- PLPA-7980: Graduate Teaching Experience - Fall 2012
- PLPA-7990: Graduate-Level Thesis Research - Fall 2012
- PLPA-8900: Master's Level Thesis Research - Fall 2012
- PLPA-9900: Doctoral-Level Thesis Research - Fall 2012
- BIOG-2990: Introduction to Research Methods in Biology - Spring 2012
- BIOG-4990: Independent Undergraduate Research in Biology - Spring 2012
- BIOMI-4811: Molecular Plant-Microbe Interactions - Spring 2012
- BIOPL-4811: Molecular Plant-Microbe Interactions - Spring 2012
- PLPA-4811: Molecular Plant-Microbe Interactions - Spring 2012
- PLPA-7980: Graduate Teaching Experience - Spring 2012
- PLPA-7990: Graduate-Level Thesis Research - Spring 2012
- PLPA-8900: Master's Level Thesis Research - Spring 2012
- PLPA-9900: Doctoral-Level Thesis Research - Spring 2012
- BIOMI-4090: Principles of Virology - Fall 2011
- BIOMS-4090: Principles of Virology - Fall 2011
- PLPA-4090: Principles of Virology - Fall 2011
- PLPA-7980: Graduate Teaching Experience - Fall 2011
- PLPA-7990: Graduate-Level Thesis Research - Fall 2011
- PLPA-8900: Master's-Level Thesis Research - Fall 2011
- PLPA-9900: Doctoral-Level Thesis Research - Fall 2011
Service
service to the profession
- American Society for Virology Member 1975 -
- AI-SPER-0203DF692AB00010840 Co-Organizer 2003 - 2008
- Program Planning Committee (Virology) for the International Union of Microbiological Societies 2005 Meeting Member 2001 - 2005
- Howard Hughes Medical Institute Program in Undergraduate Biology Education and Pre-college Outreach Program Director 2001 - 2004
- XII International Congress of Virology Organizing Committee Member 2001 - 2002
- Co-organizer NATO Advanced Study Institute on Plant Cell and Developmental Biology Program Organizer 2000 - 2001
- Organizing Committee: First International Workshop on Small DNA Viruses of Animals and Plants Member 2000 - 2001
- American Phytopathological Society Member 1989 - 1999
- Howard Hughes Medical Institute Program in Undergraduate Biology Education and Pre-college Outreach Program Director 1992 - 1998
reviewer or editor for
- ACS Proteins and Nucleic Acids
- HHMI Precollege Science
- HHMI Undergraduate Biological Sciences
- Howard Hughes Medical Institute (HHMI) and Gordon and Betty Moore Foundation (GBMF) Plant Science Investigator Awards
- NIH BIOL1 Postdoctoral Fellowship Study Section
- NIH Membrane Biology and Protein Processing
- NSF Cell Biology
- NSF Cell Biology
- NSF Eukaryotic Genetics
- NSF Research Opportunities for Women
- NSF Science and Technologies Centers
- NSF/USDA/DOE Plant Science Centers
- USAID Molecular Genetics
Background
education and training
- Ph.D. in Virology, Rockefeller University 1975
- Massachusetts Institute of Technology 1970
awards and honors
- Career Advancement Award, 1998
- Undergraduate Research Fellowship at Cold Spring Harbor Lab, 1989
- Postdoctoral Fellowship, 1975
- Predoctoral Fellowship, 1970
- Keynote Speaker, McKnight Symposium, North Carolina State University
- Symposium Speaker, American Society for Virology 19th Annual Meeting
- Symposium Speaker, 10th International Congress on Plant-Microbe Interactions
- Symposium Speaker, Society for Experimental Biology Symposium on Communication and Gene Regulation at the Nuclear Envelope
- Symposium Speaker, American Society for Virology 24th Annual Meeting
- Session Chair (organizer) and Speaker, 12th International Congress on Plant-Microbe Interactions
- Session Chair (organizer) and Speaker, 13h International Union of Microbiological Societies Congress
- Session Chair and speaker, Plant Molecular Biology Gordon
- Session Chair and speaker, International Congress on Plasmodesmata (Plasmodesmata 2006)
- Unspecified
Other
college
- CALS
research keyword
- nuclear shuttling
- plant cell-cell communication
- plant virus movement
- synaptotagmins
- vesicle trafficking
- virus-host interactions
name prefix
- Dr.