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Cynthia Burrows

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Cynthia Jane Burrows
Cynthia Burrows interviewed by the Chemical Heritage Foundation in July 2009.
Alma materUniversity of Colorado B.A. (1975)
Cornell University Ph.D. (1982)
Scientific career
ThesisSubstituent Effects on the Aliphatic Claisen Rearrangement: Synthesis and Kinetic Studies of Cyano-Substituted Allyl Vinyl Ethers (1982)
Doctoral advisorBarry Carpenter
Other academic advisorsStanley Cristol, Jean-Marie Lehn

Cynthia J. Burrows is an American chemist, currently a distinguished professor in the department of chemistry at the University of Utah, where she is also the Thatcher Presidential Endowed Chair of Biological Chemistry. Burrows was the Senior Editor of the Journal of Organic Chemistry (2001-2013) and became Editor-in-Chief of Accounts of Chemical Research in 2014.[1], [2],[3]

Education and training

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Burrows acquired a B.A. degree in chemistry at the University of Colorado (1975). There she worked on Stern-Volmer plots in Stanley Cristol's laboratory during her senior year. She continued to study physical organic chemistry at Cornell University, where she received a Ph.D. degree in chemistry in 1982 working in Barry Carpenter's laboratory. Her Ph.D. thesis work focused on cyano-substituted allyl vinyl ethers. Burrows then conducted a short post-doctoral research stint with Jean-Marie Lehn in Strasbourg, France.[4][5][6]

Career and research

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DNA can be damaged by the disruption of base pairs.

The Burrows laboratory is interested in nucleic acid chemistry, DNA sequencing technology, and DNA damage. Her research team (consisting of organic, biological, analytical and inorganic chemists) focuses on chemical processes that result in the formation of mutations, which could lead to diseases (such as cancer). Her work includes studying site-specifically modified DNA and RNA strands and DNA-protein cross linking. Burrows and her group are widely known for expanding the studies on nanopore technology by developing a method for detecting DNA damage using a nanopore.[1], [3]

One of the objectives of the Burrows Laboratory is to apply nanopore technology to identify, quantify, and analyze DNA damage brought on by oxidative stresses. Burrows focuses on the damage found in human telomeric sequences, crucial chromosomal regions that provide protection from degradation and are subject to problems during DNA replication.[7] Additionally, Burrows’ research in altering nucleic acid composition can provide valuable information in genetic diseases as well as manipulating the function of DNA and RNA in cells.

Nanopore detection of DNA damage

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The Burrows research lab focuses on detecting guanine oxidation reaction as shown.
DNA strand passes through the a-hemolysin nanopore and allows researchers to detect single base damaged site. The goal of this nanopore detection system is to locate damaged sites and understand how a damage at a specific site leads to disease.

Nanopore technology is significant in analysis of biological macromolecules such as DNA and RNA because it can detect minute sample quantities and bypasses the need for PCR amplification. PCR amplification and other DNA sequencing methods cannot detect DNA damage alone because their basis relies on the four classical unmodified bases: cytosine, adenine, guanine, and thymine. One of the most common and prevalent causes of DNA damage is oxidation of guanine residues to 8-oxoguanine brought on through oxidative stresses. 8-oxoguanine causes mismatch pairing with adenine as opposed to cytosine, which can ultimately cause point mutations during DNA replication.[8] In the context of DNA-protein cross linking, 8-oxoguanine is susceptible to forming adducts with amino acids containing reactive groups such as the phenol moiety of tyrosine or terminal amine of lysine.[9],[10] Detection and quantification of 8-oxoguanine content in telomeric sequences is important because content increases with stress since telomeres escape cellular DNA repair mechanisms.[11] Burrows helped to discover specific DNA glycosylases that preferentially repaired oxidative damages at telomeric sites.[12]

Nanopore technology relies on passing a constant electric current through a nanoscale hole immersed in an electrolytic solution. Molecules that pass through or disrupt the current by blocking the pore will generate a detectable signal when measuring current versus time. Nanopores can range from solid-state constructs to small proteins. To examine the extent of damage in G-quadruplexes of telomeres, Burrows used a protein α-hemolysin, which contains a nanoscale tube core and is embedded in the cell membrane.[11] Damaged bases are oxidatively marked with a crown ether to amplify the current signal as well as to reduce the mitigating effects of 8-oxoguanine on the native fold.[11] As the DNA strand passes through, the marked damaged base produces a characteristic signal as it disrupts the applied current.

Awards and honors

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Awards and honors include:[1]

  • NSF - CNRS Exchange of Scientists Fellowship, 1981–82
  • Japan Soc. for the Promotion of Science Research Fellow, 1989–90
  • NSF Creativity Award, 1993–95
  • NSF Career Advancement Award, 1993–94
  • Bioorganic & Natural Products Study Section, NIH, 1990–94
  • NSF Math & Physical Sciences Advisory Committee, 2005–08
  • Assoc. Editor, Organic Letters, 1999–2002
  • Senior Editor, Journal of Organic Chemistry, 2001–13
  • Robert W. Parry Teaching Award, 2002
  • ACS Utah Award, 2000
  • Bea Singer Award, 2004
  • Fellow, AAAS, 2004
  • Distinguished Scholarly and Creative Research Award, Univ. of Utah, 2005
  • Cope Scholar Award, American Chemical Society, 2008
  • Director, USTAR Governing Authority, 2009-2017
  • Member, American Academy of Arts and Sciences, 2009
  • ACS Fellow, 2010
  • Distinguished Teaching Award, 2011
  • Editor-in-Chief, Accounts of Chemical Research, 2014
  • Linda K. Amos Award for Distinguished Service to Women of U of U, 2014
  • Member, National Academy of Science, 2014
  • ACS James Flack Norris Award in Physical Organic Chemistry, 2018
  • Willard Gibbs Award, 2018

References

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  1. ^ a b c "Cynthia J. Burrows - Department of Chemistry - The University of Utah". chem.utah.edu. Retrieved 2017-05-26.
  2. ^ "Cynthia Burrows, PhD - Faculty Details - U of U School of Medicine - | University of Utah". medicine.utah.edu. Retrieved 2017-06-02.
  3. ^ a b "Cynthia Burrows". www.nasonline.org. Retrieved 2017-06-02.
  4. ^ Burrows, Cynthia J.; Carpenter, Barry K. (1981-11-01). "Substituent effects on the aliphatic Claisen rearrangement. 1. Synthesis and rearrangement of cyano-substituted allyl vinyl ethers". Journal of the American Chemical Society. 103 (23): 6983–6984. doi:10.1021/ja00413a045. ISSN 0002-7863.
  5. ^ Center for Oral History. "Cynthia J. Burrows". Science History Institute.
  6. ^ Domush, Hilary L. (16 July 2009). Cynthia J. Burrows, Transcript of an Interview Conducted by Hilary L. Domush at University of Utah, Salt Lake City, Utah on 15 and 16 July 2009 (PDF). Philadelphia, PA: Chemical Heritage Foundation.
  7. ^ An, Na; Fleming, Aaron M.; Burrows, Cynthia J. (2016-02-19). "Human Telomere G-Quadruplexes with Five Repeats Accommodate 8-Oxo-7,8-dihydroguanine by Looping out the DNA Damage". ACS Chemical Biology. 11 (2): 500–507. doi:10.1021/acschembio.5b00844. ISSN 1554-8929. PMC 4828913. PMID 26686913.
  8. ^ Cheng, K. C.; Cahill, D. S.; Kasai, H.; Nishimura, S.; Loeb, L. A. (1992-01-05). "8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G----T and A----C substitutions". The Journal of Biological Chemistry. 267 (1): 166–172. doi:10.1016/S0021-9258(18)48474-8. ISSN 0021-9258. PMID 1730583.
  9. ^ Xu, Xiaoyun; Fleming, Aaron M.; Muller, James G.; Burrows, Cynthia J. (2008-08-06). "Formation of tricyclic [4.3.3.0] adducts between 8-oxoguanosine and tyrosine under conditions of oxidative DNA-protein cross-linking". Journal of the American Chemical Society. 130 (31): 10080–10081. doi:10.1021/ja803896d. ISSN 1520-5126. PMID 18611013.
  10. ^ Xu, Xiaoyun; Muller, James G.; Ye, Yu; Burrows, Cynthia J. (2008-01-16). "DNA-protein cross-links between guanine and lysine depend on the mechanism of oxidation for formation of C5 vs C8 guanosine adducts". Journal of the American Chemical Society. 130 (2): 703–709. doi:10.1021/ja077102a. ISSN 1520-5126. PMID 18081286.
  11. ^ a b c An, Na; Fleming, Aaron M.; White, Henry S.; Burrows, Cynthia J. (2015). "Nanopore detection of 8-oxoguanine in the human telomere repeat sequence". ACS Nano. 9 (4): 4296–4307. doi:10.1021/acsnano.5b00722. ISSN 1936-086X. PMC 4790916. PMID 25768204.
  12. ^ Zhou, Jia; Liu, Minmin; Fleming, Aaron M.; Burrows, Cynthia J.; Wallace, Susan S. (2013-09-20). "Neil3 and NEIL1 DNA glycosylases remove oxidative damages from quadruplex DNA and exhibit preferences for lesions in the telomeric sequence context". The Journal of Biological Chemistry. 288 (38): 27263–27272. doi:10.1074/jbc.M113.479055. ISSN 1083-351X. PMC 3779722. PMID 23926102.
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