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Nina Papavasiliou

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Nina Papavasiliou
Alma materRockefeller University Oberlin College
AwardsSearle Scholar, NIH Director's Transformative Research Project Award, ERC Consolidator Award
Scientific career
FieldsImmunology, Molecular Biology
InstitutionsGerman Cancer Research Center, Rockefeller University, Yale University
Doctoral advisorMichel C. Nussenzweig

Nina Papavasiliou is an immunologist and Helmholtz Professor in the Division of Immune Diversity at the German Cancer Research Center in Heidelberg, Germany. She is also an adjunct professor at the Rockefeller University, where she was previously associate professor and head of the Laboratory of Lymphocyte Biology. She is best known for her work in the fields of DNA and RNA editing.

Education and early career

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Papavasiliou received her Bachelors of Science from Oberlin College in biology in 1992. She then completed her PhD at the Rockefeller University in Michel C. Nussenzweig's Laboratory of Molecular Immunology. There, she began studying how B cell antigen receptors—or antibodies anchored to the cell membrane—undergo mutation so they can specifically recognize a particular antigen and elicit an immune response.[1][2] She followed that interest to the Yale School of Medicine, where she worked as a postdoctoral fellow in the lab of David G. Schatz.[3][4]

Research

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Papavasiliou's research centers on demystifying how cells and organisms diversify and expand the information encoded in their genomes, both at the DNA and RNA level. She opened her Laboratory of Lymphocyte Biology at Rockefeller University in 2001 as an assistant professor.[5] Much of her group's early work was done in the context of the adaptive immune response, which is able to combat a wide array of pathogens seeking to invade the host by rapidly generating novel antibodies that are able to specifically recognize a given invader. Her group has worked to characterize the activity of an enzyme known as activation-induced cytidine deaminase (AID).[6][7] AID changes cytidine (C) residues to uracil (U) in DNA, which is recognized as DNA damage and repaired in such a way that introduces thymidine (T), effectively mutating Cs to Ts in DNA. The process is known as somatic hypermutation and is how B cells can rapidly introduce DNA mutations into receptors that recognize the invaders, known as antigens. Papavasiliou's lab has worked to understand how AID expression is regulated in the immune system and how AID targets certain genes for mutation.[8][9][10]

Papavasiliou also studies RNA editing in the context of the innate immune response using next-generation sequencing and bioinformatics approaches to identify and characterize RNA editing targets. Her group first identified novel RNA editing targets of APOBEC1, which mutates a cytosine to a uracil in an RNA transcript, and was previously thought to only edit Apolipoprotein B (apoB) in the small intestine.[11] Her group has since moved on to attempt to characterize the potential role APOBEC1-editing may be playing outside of its function with apoB.[12]

Papavasiliou most recently branched out to studying mechanisms of antigenic variation—or how pathogens vary their surface proteins to escape the immune response—using Trypanosoma brucei, the parasite that causes African sleeping sickness, as a model organism. Her group has developed new tools to better understand the dynamics of protein coat switching in trypanosomes, and is working to better understand the mechanisms by which trypanosomes are able to diversify their coat proteins over the course of an infection.[13][14][15]

In 2016, Papavasiliou moved to the German Cancer Research Center to begin her lab in the Division of Immune Diversity with additional support from a European Research Council Consolidator Grant.[16][17]

Award & honors

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References

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  1. ^ Papavasiliou, Fotini; Jankovic, Mila; Gong, Shiaoching; Nussenzweig, Michel C. (1997-04-01). "Control of immunoglobulin gene rearrangements in developing B cells". Current Opinion in Immunology. 9 (2): 233–238. doi:10.1016/S0952-7915(97)80141-0. ISSN 0952-7915. PMID 9099793.
  2. ^ Papavasiliou, Fotini; Casellas, Rafael; Suh, Heikyung; Qin, Xiao-Feng; Besmer, Eva; Pelanda, Roberta; Nemazee, David; Rajewsky, Klaus; Nussenzweig, Michel C. (1997-10-10). "V(D)J Recombination in Mature B Cells: A Mechanism for Altering Antibody Responses". Science. 278 (5336): 298–301. doi:10.1126/science.278.5336.298. ISSN 0036-8075. PMID 9323210.
  3. ^ Papavasiliou, F. Nina; Schatz, David G. (November 2000). "Cell-cycle-regulated DNA double-strand breaks in somatic hypermutation of immunoglobulin genes". Nature. 408 (6809): 216–221. doi:10.1038/35041599. ISSN 0028-0836. PMID 11089977. S2CID 4407389.
  4. ^ Papavasiliou, F.Nina; Schatz, David G (April 2002). "Somatic Hypermutation of Immunoglobulin Genes". Cell. 109 (2): S35–S44. doi:10.1016/S0092-8674(02)00706-7. ISSN 0092-8674. PMID 11983151. S2CID 15533869.
  5. ^ "F. Nina Papavasiliou - Our Scientists". Our Scientists. Archived from the original on 2018-07-03. Retrieved 2018-07-03.
  6. ^ Dickerson, Sarah K.; Market, Eleonora; Besmer, Eva; Papavasiliou, F. Nina (2003-05-19). "AID mediates hypermutation by deaminating single stranded DNA". The Journal of Experimental Medicine. 197 (10): 1291–1296. doi:10.1084/jem.20030481. ISSN 0022-1007. PMC 2193777. PMID 12756266.
  7. ^ Besmer, Eva; Market, Eleonora; Papavasiliou, F. Nina (June 2006). "The transcription elongation complex directs activation-induced cytidine deaminase-mediated DNA deamination". Molecular and Cellular Biology. 26 (11): 4378–4385. doi:10.1128/MCB.02375-05. ISSN 0270-7306. PMC 1489098. PMID 16705187.
  8. ^ Crouch, Elizabeth E.; Li, Zhiyu; Takizawa, Makiko; Fichtner-Feigl, Stefan; Gourzi, Polyxeni; Montaño, Carolina; Feigenbaum, Lionel; Wilson, Patrick; Janz, Siegfried (2007-05-14). "Regulation of AID expression in the immune response". The Journal of Experimental Medicine. 204 (5): 1145–1156. doi:10.1084/jem.20061952. ISSN 0022-1007. PMC 2118564. PMID 17452520.
  9. ^ Teng, Grace; Hakimpour, Paul; Landgraf, Pablo; Rice, Amanda; Tuschl, Thomas; Casellas, Rafael; Papavasiliou, F. Nina (May 2008). "MicroRNA-155 is a negative regulator of activation-induced cytidine deaminase". Immunity. 28 (5): 621–629. doi:10.1016/j.immuni.2008.03.015. ISSN 1097-4180. PMC 2430982. PMID 18450484.
  10. ^ Delker, Rebecca K.; Zhou, Yanjiao; Strikoudis, Alexandros; Stebbins, C. Erec; Papavasiliou, F. Nina (2013-01-15). "Solubility-based genetic screen identifies RING finger protein 126 as an E3 ligase for activation-induced cytidine deaminase". Proceedings of the National Academy of Sciences of the United States of America. 110 (3): 1029–1034. doi:10.1073/pnas.1214538110. ISSN 1091-6490. PMC 3549133. PMID 23277564.
  11. ^ Rosenberg, Brad R.; Hamilton, Claire E.; Mwangi, Michael M.; Dewell, Scott; Papavasiliou, F. Nina (February 2011). "Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3' UTRs". Nature Structural & Molecular Biology. 18 (2): 230–236. doi:10.1038/nsmb.1975. ISSN 1545-9985. PMC 3075553. PMID 21258325.
  12. ^ Rayon-Estrada, Violeta; Harjanto, Dewi; Hamilton, Claire E.; Berchiche, Yamina A.; Gantman, Emily Conn; Sakmar, Thomas P.; Bulloch, Karen; Gagnidze, Khatuna; Harroch, Sheila (December 12, 2017). "Epitranscriptomic profiling across cell types reveals associations between APOBEC1-mediated RNA editing, gene expression outcomes, and cellular function". Proceedings of the National Academy of Sciences of the United States of America. 114 (50): 13296–13301. doi:10.1073/pnas.1714227114. ISSN 1091-6490. PMC 5740640. PMID 29167373.
  13. ^ "Parasite Breaks Its Own DNA To Avoid Detection". ScienceDaily. Retrieved 2018-07-03.
  14. ^ "Study suggests new way to help the immune system fight off sleeping sickness parasite". EurekAlert!. Retrieved 2018-07-03.
  15. ^ "Study suggests new way to help the immune system fight off parasite". EurekAlert!. Retrieved 2018-07-03.
  16. ^ "Immune Diversity". www.dkfz.de. Retrieved 2018-07-03.
  17. ^ "ERC FUNDED PROJECTS". ERC: European Research Council. Retrieved 2018-07-03.
  18. ^ "F. Nina Papavasiliou - Our Scientists". Our Scientists. Archived from the original on 2018-10-11. Retrieved 2018-10-10.
  19. ^ "Searle Scholars Program : F. Nina Papavasiliou (2003)". www.searlescholars.net. Archived from the original on 2018-07-03. Retrieved 2018-07-03.
  20. ^ "F. Nina Papavasiliou - Our Scientists". Our Scientists. Archived from the original on 2018-10-11. Retrieved 2018-10-10.
  21. ^ Holland, Jennifer. "G. Jeanette Thorbecke Award". www.leukocytebiology.org. Retrieved 2018-07-03.
  22. ^ "The Vilcek Foundation - Finalists". www.vilcek.org. Archived from the original on 2018-07-03. Retrieved 2018-07-03.
  23. ^ generator, metatags. "Project Information - NIH RePORTER - NIH Research Portfolio Online Reporting Tools Expenditures and Results". projectreporter.nih.gov. Retrieved 2018-07-03.