Nina Papavasiliou

Last updated
Nina Papavasiliou
Nina Papavasiliou at The Rockefeller University.jpg
Alma mater Rockefeller University Oberlin College
Awards Searle Scholar, NIH Director's Transformative Research Project Award, ERC Consolidator Award
Scientific career
Fields Immunology, Molecular Biology
Institutions German Cancer Research Center, Rockefeller University, Yale University
Doctoral advisor Michel 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.

Contents

Education and early career

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

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

Related Research Articles

In immunology, affinity maturation is the process by which TFH cell-activated B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities. A secondary response can elicit antibodies with several fold greater affinity than in a primary response. Affinity maturation primarily occurs on membrane immunoglobulin of germinal center B cells and as a direct result of somatic hypermutation (SHM) and selection by TFH cells.

<span class="mw-page-title-main">Activation-induced cytidine deaminase</span> Enzyme that creates mutations in DNA

Activation-induced cytidine deaminase, also known as AICDA, AID and single-stranded DNA cytosine deaminase, is a 24 kDa enzyme which in humans is encoded by the AICDA gene. It creates mutations in DNA by deamination of cytosine base, which turns it into uracil. In other words, it changes a C:G base pair into a U:G mismatch. The cell's DNA replication machinery recognizes the U as a T, and hence C:G is converted to a T:A base pair. During germinal center development of B lymphocytes, AID also generates other types of mutations, such as C:G to A:T. The mechanism by which these other mutations are created is not well understood. It is a member of the APOBEC family.

<span class="mw-page-title-main">APOBEC3G</span> Protein and coding gene in humans

APOBEC3G is a human enzyme encoded by the APOBEC3G gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important role in innate anti-viral immunity. APOBEC3G belongs to the family of cytidine deaminases that catalyze the deamination of cytidine to uridine in the single stranded DNA substrate. The C-terminal domain of A3G renders catalytic activity, several NMR and crystal structures explain the substrate specificity and catalytic activity.

<span class="mw-page-title-main">Immunoglobulin class switching</span> Biological mechanism

Immunoglobulin class switching, also known as isotype switching, isotypic commutation or class-switch recombination (CSR), is a biological mechanism that changes a B cell's production of immunoglobulin from one type to another, such as from the isotype IgM to the isotype IgG. During this process, the constant-region portion of the antibody heavy chain is changed, but the variable region of the heavy chain stays the same. Since the variable region does not change, class switching does not affect antigen specificity. Instead, the antibody retains affinity for the same antigens, but can interact with different effector molecules.

<span class="mw-page-title-main">PSME4</span> Protein found in humans

Proteasome activator complex subunit 4 is a protein that in humans is encoded by the PSME4 gene.

<span class="mw-page-title-main">APOBEC1</span>

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 also known as C->U-editing enzyme APOBEC-1 is a protein that in humans is encoded by the APOBEC1 gene.

<span class="mw-page-title-main">Cytidine deaminase</span> Protein-coding gene in the species Homo sapiens

Cytidine deaminase is an enzyme that in humans is encoded by the CDA gene.

<span class="mw-page-title-main">APOBEC3F</span>

DNA dC->dU-editing enzyme APOBEC-3F is a protein that in humans is encoded by the APOBEC3F gene.

<span class="mw-page-title-main">APOBEC3C</span> Protein-coding gene in humans

DNA dC->dU-editing enzyme APOBEC-3C is a protein that in humans is encoded by the APOBEC3C gene.

<span class="mw-page-title-main">APOBEC2</span> Protein-coding gene in the species Homo sapiens

Probable C->U-editing enzyme APOBEC-2 is a protein that in humans is encoded by the APOBEC2 gene.

<span class="mw-page-title-main">APOBEC3A</span>

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A, also known as APOBEC3A, or A3A is a gene of the APOBEC3 family found in humans, non-human primates, and some other mammals. It is a single-domain DNA cytidine deaminase with antiviral effects. While other members of the family such as APOBEC3G are believed to act by editing ssDNA by removing an amino group from cytosine in DNA, introducing a cytosine to uracil change which can ultimately lead to a cytosine to thymine mutation, one study suggests that APOBEC3A can inhibit parvoviruses by another mechanism. The cellular function of APOBEC3A is likely to be the destruction of foreign DNA through extensive deamination of cytosine.Stenglein MD, Burns MB, Li M, Lengyel J, Harris RS. "APOBEC3 proteins mediate the clearance of foreign DNA from human cells". Nature Structural & Molecular Biology. 17 (2): 222–9. doi:10.1038/nsmb.1744. PMC 2921484. PMID 20062055.

<span class="mw-page-title-main">APOBEC3B</span>

Probable DNA dC->dU-editing enzyme APOBEC-3B is a protein that in humans is encoded by the APOBEC3B gene.

<span class="mw-page-title-main">APOBEC3D</span>

Probable DNA dC->dU-editing enzyme APOBEC-3D is a protein that in humans is encoded by the APOBEC3D gene.

<span class="mw-page-title-main">APOBEC</span> Enzyme involved in messenger RNA editing

APOBEC is a family of evolutionarily conserved cytidine deaminases.

<span class="mw-page-title-main">APOBEC3H</span>

DNA dC->dU-editing enzyme APOBEC-3H, also known as Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3H or APOBEC-related protein 10, is a protein that in humans is encoded by the APOBEC3H gene.

<span class="mw-page-title-main">APOBEC4</span> Protein-coding gene in the species Homo sapiens

C->U-editing enzyme APOBEC-4, also known as Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 4, is a protein that in humans is encoded by the APOBEC4 gene. It is primarily expressed in testis and found in mammals, chicken, but not fishes.

Somatic hypermutation is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it, as seen during class switching. A major component of the process of affinity maturation, SHM diversifies B cell receptors used to recognize foreign elements (antigens) and allows the immune system to adapt its response to new threats during the lifetime of an organism. Somatic hypermutation involves a programmed process of mutation affecting the variable regions of immunoglobulin genes. Unlike germline mutation, SHM affects only an organism's individual immune cells, and the mutations are not transmitted to the organism's offspring. Because this mechanism is merely selective and not precisely targeted, somatic hypermutation has been strongly implicated in the development of B-cell lymphomas and many other cancers.

<span class="mw-page-title-main">Kataegis</span>

In molecular biology, kataegis describes a pattern of localized hypermutations identified in some cancer genomes, in which a large number of highly patterned basepair mutations occur in a small region of DNA. The mutational clusters are usually several hundred basepairs long, alternating between a long range of C→T substitutional pattern and a long range of G→A substitutional pattern. This suggests that kataegis is carried out on only one of the two template strands of DNA during replication. Compared to other cancer-related mutations, such as chromothripsis, kataegis is more commonly seen; it is not an accumulative process but likely happens during one cycle of replication.

Jawless vertebrates, which today consist entirely of lampreys and hagfish, have an adaptive immune system similar to that found in jawed vertebrates. The cells of the agnathan AIS have roles roughly equivalent to those of B-cells and T-cells, with three lymphocyte lineages identified so far:

Viviana Simon is a Professor of Microbiology at the Icahn School of Medicine at Mount Sinai (ISMMS). She is a member of the ISMMS Global Health and Emerging Pathogens Institute. Her research considers viral-host interactions and the mode of action of retroviral restriction factors. During the COVID-19 pandemic, Simon developed an antibody test that can determine immunity to Coronavirus disease 2019.

References

  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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.