Rebecca Abergel

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Rebecca Abergel grew up near Paris, France where she received her undergraduate degree from École Normale Supérieure in 2002. While an undergraduate, she received a scholarship to work under Professor John Arnold, an inorganic chemist from the University of California, Berkeley. She eventually pursued her graduate degree in bio-inorganic chemistry from the University of California Berkeley in 2006 working in the group of Ken Raymond. Abergel currently holds joint positions as a staff scientist at Lawrence Berkeley National Laboratory in Berkeley, California and Assistant Professor of Nuclear Engineering at University of California, Berkeley.[1]

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.[1] Her group is especially active in developing therapeutics to treat people who have been exposed to radionuclides or atoms that contain excess nuclear charge. These radionuclides can include plutonium, americium, curium, uranium, plutonium, and neptunium. Recent work by the BioActinide Research group has involved synthesis of different actinide chelating agents that could be used to selectively bind radionuclides in the human body in order to safely remove them.[2]

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 is treating plutonium poisoning, but this treatment is specific only to plutonium.[3] 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 moieties (Figure 2). This molecule is unique in having the potential for oral consumption in humans.[4] 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.[3]

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

The chelator of interest exhibits higher affinity for lanthanides in vivo than DTPA due to its octadentate structure, and thus it has shown greater efficacy in radionuclide decorporation in living systems.[5] 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.[6] Finally, in a separate study, Abergel evaluated the purity of this molecule for potential drug applications, ultimately bringing this effort closer to the development of a deployable treatment solution.[7]

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.[8] Overall, this work, along with further studies focusing on lanthanide and actinide chelation, has important implications for medicinal and environmental chemistry.[9][10]

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. ^ a b "Women @ The Lab". 2013.
  2. ^ 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.
  3. ^ a b "Rebecca Abergel".
  4. ^ 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.
  5. ^ 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". SciTech Connect. 40 (33): 8340–6. doi:10.1039/c1dt10840a. PMID 21766096.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ "Curious curium". Nature Chemistry. 2016-04-22.
  10. ^ 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.