Rebecca Abergel

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Rebecca Abergel
Rebecca Abergel.jpg
Alma materÉcole Normale Supérieure (B.Sc.) (2002)
University of California, Berkeley (Ph.D) (2006)
Scientific career
FieldsCoordination Chemistry, Environmental Chemistry
InstitutionsUniversity of California, Berkeley
Doctoral advisorKen Raymond
Websiteabergel.lbl.gov

Rebecca Abergel is a French inorganic chemist who specializes in the coordination chemistry between lanthanide and actinide complexes. Alongside the effects of heavy element exposure and contamination on different biological systems. Abergel is currently a Faculty Scientist and Heavy Element Chemistry Group Leader at the Chemical Sciences Division of Lawrence Berkeley National Laboratory in Berkeley, California. She is also Assistant Professor of Nuclear Engineering at University of California, Berkeley.[1][2]

Early life and education[edit]

Abergel grew up near Paris, France, where she received her undergraduate degree in Chemistry from École Normale Supérieure in 2002. While an undergraduate, she received a scholarship to work under Prof. John Arnold, an inorganic chemist at the University of California, Berkeley.[3]

She then pursued graduate studies at UC Berkeley, where she worked with Prof. Ken Raymond. For her doctoral work, she synthesised and characterised siderophore analogs to investigate how bacteria transport iron and to develop new iron chelating agents.[3][4][5][6][7][8] Abergel graduated in 2006 with her Ph.D. in Chemistry.[2]

Abergel was a joint postdoctoral researcher between the UC Berkeley Department of Chemistry and the group of Prof. Roland Strong at the Fred Hutchinson Cancer Research Center. Here she investigated how siderocalin binds to siderophores from bacteria such as Bacillus anthracis, for the development of new antibiotics.[9][10][11]

Dr. Abergel joined Berkeley Lab in 2009, she received a Young Investigator Award from the Cooley's Anemia Foundation in 2009, a Junior Faculty Travel Award from the Radiation Research Society in 2013, and a Director's Award for Exceptional Scientific Achievement from Berkeley Lab in 2013.

Research interests[edit]

Abergel's BioActinide Research group conducts a variety of different experiments in the field of coordination chemistry, analytical chemistry, photophysics, biological chemistry, health physics, pharmacology, molecular biology, and cell biology. More specifically, her recent interests have focused on the coordination behavior of lanthanides and actinides.[12] Her group is especially active in developing healing methods to treat people who have been exposed to radionuclides or atoms that contain excess nuclear charge. In recent work by the BioActinide Research group, different actinide chelating agents have been synthesised which could be used to selectively bind radionuclides in the human body in order to safely remove them.[13]

Figure 1 - DTPA

Currently, the only drug approved by the Food and Drug Administration to treat radionuclide contamination is diethylenetriaminepentaacetic acid (DTPA) (Figure 1). DTPA has shown some promise in treating plutonium poisoning, but this treatment is specific only to plutonium.[14] Furthermore, DTPA must be administered intravenously, which is an issue due to the extremely time-sensitive nature of radiation poisoning. In the quest of finding a more versatile and easily administered treatment for radiation poisoning, Abergel sees potential in developing new classes of therapeutics.

The agent under investigation is an octadentate ligand consisting of four cross-linked dipicolinic acid components (Figure 2). This molecule is unique in having the potential for oral consumption in humans.[15] It would function by coordinating as a chelating ligand with toxic actinides in the body before they can cause significant damage. In theory, once the chelating ligands have bound to the actinides, the heavy metal complexes can exit the body naturally by urination.[14]

Figure 2 - 3,4,3-LI(1,2-HOPO)

Due to its octadentate structure, the chelator of interest exhibits higher affinity for lanthanides in vivo than DTPA. Therefore, it has demonstrated better radionuclide decorporation in living systems.[16] The ligand has shown favorable selectivity for plutonium, americium, uranium, and neptunium decorporation (with no observed toxicity in either in vitro tests on human tissue or in vivo experiments on rodent models), which is also an improvement over the currently accepted DTPA.[17] Finally, in a separate study, Abergel evaluated the purity of this molecule for use as a drug, ultimately bringing this effort closer to the development of a deployable treatment solution.[18]

Figure 3 - 5-LIO(Me-3,2-HOPO)

An additional research project by Abergel's group involved testing the effectiveness of other analogs containing dipicolinic acid in eliminating plutonium (Figure 3). Results showed that both of the compounds were successful in removing plutonium over a seven-day period in mice.[19] Overall, this work, along with further studies focusing on lanthanide and actinide chelation, has important implications for medicinal and environmental chemistry.[20][21]

Awards and fellowships[edit]

  • Directors Award for Exceptional Scientific Achievement (2013), Lawrence Berkeley National Laboratory, USA
  • Junior Faculty NCRP Award (2013), Radiation Research Society, USA
  • Young Investor Research Fellowship (2009-2010), Cooley's Anemia Foundation, New York, NY, USA
  • European Commission Marie Curie Actions Scholarship (2004), European School of Haematology, France
  • Université Pierre et Marie Curie Annual Fellowship (2002), French Conseil Régional d’Ile de France, France

References[edit]

  1. ^ "People". abergel.lbl.gov. Retrieved 2021-05-18.
  2. ^ a b "Rebecca Abergel - Chemical Sciences Division Chemical Sciences Division". commons.lbl.gov. Retrieved 2021-05-18.
  3. ^ a b "Women @ The Lab - Rebecca Abergel, Ph.D." sites.google.com. Retrieved 2021-05-18.
  4. ^ Abergel, Rebecca J.; Raymond, Kenneth N. (2006-05-01). "Synthesis and Thermodynamic Evaluation of Mixed Hexadentate Linear Iron Chelators Containing Hydroxypyridinone and Terephthalamide Units1". Inorganic Chemistry. 45 (9): 3622–3631. doi:10.1021/ic052111a. ISSN 0020-1669. PMC 3685440. PMID 16634594.
  5. ^ Abergel, Rebecca J.; Warner, Jeffrey A.; Shuh, David K.; Raymond, Kenneth N. (2006-07-01). "Enterobactin Protonation and Iron Release: Structural Characterization of the Salicylate Coordination Shift in Ferric Enterobactin1". Journal of the American Chemical Society. 128 (27): 8920–8931. doi:10.1021/ja062046j. ISSN 0002-7863. PMC 3188320. PMID 16819888.
  6. ^ Abergel, Rebecca J.; Raymond, Kenneth N. (2008-02-01). "Terephthalamide-containing ligands: fast removal of iron from transferrin". JBIC Journal of Biological Inorganic Chemistry. 13 (2): 229–240. doi:10.1007/s00775-007-0314-y. ISSN 1432-1327. PMID 17990009. S2CID 20706644.
  7. ^ Abergel, Rebecca J.; Zawadzka, Anna M.; Raymond, Kenneth N. (2008-02-01). "Petrobactin-Mediated Iron Transport in Pathogenic Bacteria: Coordination Chemistry of an Unusual 3,4-Catecholate/Citrate Siderophore". Journal of the American Chemical Society. 130 (7): 2124–2125. doi:10.1021/ja077202g. ISSN 0002-7863. PMID 18220393.
  8. ^ Abergel, Rebecca J.; Zawadzka, Anna M.; Hoette, Trisha M.; Raymond, Kenneth N. (2009-09-09). "Enzymatic Hydrolysis of Trilactone Siderophores: Where Chiral Recognition Occurs in Enterobactin and Bacillibactin Iron Transport". Journal of the American Chemical Society. 131 (35): 12682–12692. doi:10.1021/ja903051q. ISSN 0002-7863. PMC 2782669. PMID 19673474.
  9. ^ Abergel, Rebecca J.; Moore, Evan G.; Strong, Roland K.; Raymond, Kenneth N. (2006-08-01). "Microbial Evasion of the Immune System: Structural Modifications of Enterobactin Impair Siderocalin Recognition". Journal of the American Chemical Society. 128 (34): 10998–10999. doi:10.1021/ja062476+. ISSN 0002-7863. PMC 3188317. PMID 16925397.
  10. ^ Abergel, Rebecca J.; Wilson, Melissa K.; Arceneaux, Jean E. L.; Hoette, Trisha M.; Strong, Roland K.; Byers, B. Rowe; Raymond, Kenneth N. (2006-12-05). "Anthrax pathogen evades the mammalian immune system through stealth siderophore production". Proceedings of the National Academy of Sciences. 103 (49): 18499–18503. Bibcode:2006PNAS..10318499A. doi:10.1073/pnas.0607055103. ISSN 0027-8424. PMC 1693691. PMID 17132740.
  11. ^ Abergel, Rebecca J.; Clifton, Matthew C.; Pizarro, Juan C.; Warner, Jeffrey A.; Shuh, David K.; Strong, Roland K.; Raymond, Kenneth N. (2008-08-27). "The Siderocalin/Enterobactin Interaction: A Link between Mammalian Immunity and Bacterial Iron Transport1". Journal of the American Chemical Society. 130 (34): 11524–11534. doi:10.1021/ja803524w. ISSN 0002-7863. PMC 3188318. PMID 18680288.
  12. ^ "Women @ The Lab". 2013.
  13. ^ Jarvis, Erin E.; An, Dahlia D.; Kullgren, Birgitta; Abergel, Rebecca J. (2012). "Significance of Single Variables in Defining Adequate Animal Models to Assess the Efficacy of New Radionuclide Decorporation Agents: Using the Contamination Dose as an Example". Drug Development Research. 73 (5): 281–289. doi:10.1002/ddr.21020. S2CID 82740785.
  14. ^ a b "Rebecca Abergel".
  15. ^ Choi, Taylor A.; Furimsky, Anna M.; Swezey, Robert; Bunin, Deborah I.; Byrge, Patricia; Iyer, Lalitha V.; Chang, Polly Y.; Abergel, Rebecca J. (2015). "In Vitro Metabolism and Stability of the Actinide Chelating Agent 3,4,3-LI(1,2-HOPO)". Journal of Pharmaceutical Sciences. 104 (5): 1832–1838. doi:10.1002/jps.24394. PMC 4390475. PMID 25727482.
  16. ^ Sturzbecher-Hoehne, Manuel; Ng Pak Leung, Clara; d'Aléo, Anthony; Kullgren, Birgitta; Prigent, Anne-Laure; Shuh, David K.; Raymond, Kenneth N.; Abergel, Rebecca J. (2011). "3,4,3-LI(1,2-HOPO): In Vitro Formation of Highly Stable Lanthanide Complexes Translates into Efficacious In Vivo Europium Decorporation" (PDF). Dalton Transactions. 40 (33): 8340–6. doi:10.1039/c1dt10840a. OSTI 1051843. PMID 21766096.
  17. ^ Abergel, R. J.; Durbin, P. W.; Kullgren, B.; Ebbe, S. N.; Xu, J.; Chang, P. Y.; Bunin, D. I.; Blakely, E. A.; Bjornstad, K. A.; Rosen, C. J.; Shuh, D. K.; Raymond, K. N. (2010). "Biomimetic Actinide Chelators: An Update on the Preclinical Development of the Orally Active Hydroxypyridonate Decorporation Agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO)". Health Phys. 99 (3): 401–407. doi:10.1097/HP.0b013e3181c21273. PMC 2921233. PMID 20699704.
  18. ^ Panyala, Nagender R.; Sturzbecher-Hoehne, Manuel; Abergel, Rebecca J. (2014). "Identification of process related trace level impurities in the actinide decorporation agent 3,4,3-LI(1,2-HOPO): Nozzle–skimmer fragmentation via ESI LC–QTOFMS". Journal of Pharmaceutical and Biomedical Analysis. 100: 157–166. doi:10.1016/j.jpba.2014.08.004. PMC 4179986. PMID 25165012.
  19. ^ An, Dahlia D.; Kullgren, Birgitta; Jarvis, Erin E.; Abergel, Rebecca J. (2017). "From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents". Chemico-Biological Interactions. 267: 80–88. doi:10.1016/j.cbi.2016.03.034. PMC 5045775. PMID 27038878.
  20. ^ Abergel, Rebecca J.; Ansoborlo, Eric (2016-04-22). "Curious curium". Nature Chemistry. 8 (5): 516. Bibcode:2016NatCh...8..516A. doi:10.1038/nchem.2512. OSTI 1458477. PMID 27102687.
  21. ^ Deblonde, Gauthier J-P.; Sturzbecher-Hoehne, Manuel; Abergel, Rebecca J. (2013). "Solution Thermodynamic Stability of Complexes Formed with the Octadentate Hydroxypyridinonate Ligand 3,4,3-LI(1,2-HOPO): A Critical Feature for Efficient Chelation of Lanthanide(IV) and Actinide(IV) Ions". Inorganic Chemistry. 52 (15): 8805–8811. doi:10.1021/ic4010246. PMC 3771511. PMID 23855806.