“A coin has two sides”

Professor Cynthia J. Burrows

“A coin has two sides” As a keynote speaker of this year’s ACS TOXI meeting, Cynthia J. Burrows emphasized the idea that DNA damage can have both positive and negative impacts on human health. This novel idea is the main driving force of her research. Since her undergraduate studies in physical organic chemistry with Prof. Stan Cristol, chemistry and chemical biology have been her main interests. Her Ph.D. work with Prof. Barry Carpenter at Cornell University and her postdoctoral studies with Nobel Laureate Prof. Jean-Marie Lehn at Louis Pasteur University strengthened her passion for research. Dr. Burrows was the first woman on the chemistry faculty at the State University of New York, where she was rapidly promoted to full professor. In 1995, she shifted to the University of Utah, where she is currently a Distinguished Professor of Chemistry. The Burrows lab’s research seeks to understand the processes of oxidative damage to DNA and its biological consequences. Dr. Burrows received several awards for her outstanding and groundbreaking contributions to the field of DNA damage. Dr. Burrows’s research was acknowledged by two ACS awards: the Cope Scholar Award and the James Flack Norris Award in Physical Organic Chemistry. In 2014, she was elected to the National Academy of Sciences. She also won the Rosenblatt Prize for Excellence from the University of Utah, and both the Robert Parry Teaching and Distinguished Teaching Awards for her extraordinary instructorship. She has also been a member of assorted review panels as well as editorial boards. She worked as Associate Editor of Organic Letters as well as Senior Editor of The Journal of Organic Chemistry. Currently, she is Editor-in-Chief of Accounts of Chemical Research. Apart from research and teaching awards, she was also awarded a Linda K. Amos Award for Distinguished Service to Women. She tries to encourage diversity in science and serves as a role model for women. When asked for the reason for being selected as a TOXI keynote speaker, Dr. Burrows refers to ∼30 years of research in the field of DNA damage and repair. She mentioned that our recent understanding of the cellular roles of DNA damage extends beyond mutagenesis and that some chemical modifications of DNA make up a natural process in the cell. Oxidation of guanine is anomalous and can be mutagenic, but we cannot exclude the positive aspect of this modification in cellular processes. Other events could be beneficial such as epigenetic modifications, 5-methyl-C and N⁷-methyl-G (from mRNA). Delighted by this keynote speaker opportunity, she emphasizes that “as a scientist, I got the chance to share my key discoveries. This depth of understanding is coming from the persistent efforts of my colleagues and collaborators.” Dr. Burrows’s love for solving puzzles motivated her to pursue a career in academia. Her puzzle-solving strategy involves asking “why?” and “what is important?”. She focuses on the basic mechanisms of a process to answer specific research questions. In her opinion, industry often lacks flexibility, while academia offers more freedom to work on specific fields of interest and allows her to branch out with various collaborations. Two aspects of making contributions as a successful researcher to the world are important for her. The very first is to figure things out. In this context, she emphasizes a basic understanding of chemical reactions and biochemical aspects such as how cells work. This approach is necessary for understanding and solving long-lasting medical problems at a primary level. Her second important aspect is to train the next generation. It is a huge responsibility to lead them down the right path. “We have a great system; new people are constantly coming to the lab and it’s always a privilege to learn together with a group of young and dynamic people”, Dr. Burrows added. While discussing her most important research findings, she mentioned that oxidized bases can have an epigenetic function, particularly if taking place within G-rich gene promoter sequences, where they impact gene expression coordinated by the base excision repair pathway. This finding changes our view of 8-oxo-dG, which is simply not a damaged DNA base, but, if found in G-quadruplexes, may also turn on gene expression. She said that this may be the most important finding of her research career. This result comes from her continuous efforts to understand the chemistry of guanine oxidation relevant to cellular chemistry and examining the folding dynamics of G-rich sequences that form G-quadruplexes. Further, Dr. Burrows has a long-term goal in understanding the two-way role of oxidative DNA damage at the whole-genome level. These experiments include oxidation at the model plasmid level (using cell-based assays to understand the impact of DNA modifications on G-expression), improving methods for sequencing, and most importantly understanding the various protein interactions as well as the choreography between key components during repair mechanisms of oxidative DNA damage. It also involves determining the interplay of chemical modifications in DNA (and RNA) with structural motifs such as G-quadruplexes. When asked about which skills and experiences contributed the most to her professional success, Dr. Burrows gave credit to her colleagues, collaborators, students, and postdocs. She said it is always fascinating working around good people and experts from different fields. Further, she mentioned that it is important to have the ability to move and evolve as a scientist, to keep branching out, and to gain new perspectives. For instance, she began her work on small molecules during her Ph.D. and is now working on biomolecules. “I simply enjoy doing research”, Dr. Burrows added. Two large transitions have turned out to be defining moments for her as a scientist: first, she trained as a physical organic chemist; second, her work on DNA reactions as well as gaining insights on HPLC purification, mass spectrometry, and gel electrophoresis work in the field of DNA damage. She is thankful to friends, colleagues, and collaborators all over the world for helping her through her research journey. She added that maintaining a work–life balance was challenging: “I have three kids...my husband and I always had to have schedules. We both used to work Monday to Friday. For Saturdays, we had a schedule to take care of our kids, in such a way that I used to work in the morning half while my husband used to do his work in the afternoon. Sunday was a family day!” To manage work–life balance, she suggested accomplishing big things first and shared the inspiring story “Precious Stones” from the book: “Who Ordered This Truckload of Dung?: Inspiring Stories for Welcoming Life Difficulties,” by Ajahn Brahm. Currently, her daily routine includes a combination of teaching, research, and meetings. She teaches Biochemistry to a class of 400 students that involves six different discussion sections. It is a big change due to COVID-19 since she needs to be much more prepared in advance. Dr. Burrows added further that research is also happening through group meetings over Zoom. She also spends a significant portion of her time on editorial work as well as on grant writing. She noted, however, that the social aspect is missing from her academic community. Apart from research, she enjoys cooking: “I like to make jam,” she said. She also likes hiking, biking, and skiing in the winter. Lastly, Dr. Burrows gave advice to young scientists: “be an optimist and enjoy the work! Doing science and doing it well can be a thrill or frustrating. Don’t think that the experiment didn’t work, turn failure to success by asking why, and try to listen to what the data is saying. Maybe the data wants to say something different and could open new doors for great innovations. Be smart, persistent, and flexible. Follow the literature. It is your friend.” This article has not yet been cited by other publications.

中文翻译：

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采访 Cynthia J. Burrows 教授，2020 年美国化学学会化学毒理学分会主旨演讲人

“硬币有两个面”

辛西娅·J·伯罗斯教授

“一枚硬币有两个面” 作为今年 ACS TOXI 会议的主旨发言人，Cynthia J. Burrows 强调了 DNA 损伤对人类健康既有积极影响也有消极影响的观点。这种新颖的想法是她研究的主要动力。自从她跟随 Stan Cristol 教授攻读物理有机化学本科以来，化学和化学生物学一直是她的主要兴趣。她的博士学位 与康奈尔大学 Barry Carpenter 教授的合作以及她在路易斯巴斯德大学与诺贝尔奖获得者 Jean-Marie Lehn 教授的博士后研究增强了她对研究的热情。Burrows 博士是纽约州立大学化学系的第一位女性，并迅速晋升为正教授。1995 年，她转到犹他大学，目前是该校的杰出化学教授。Burrows 实验室的研究旨在了解 DNA 氧化损伤的过程及其生物学后果。Burrows 博士因其在 DNA 损伤领域的杰出和开创性贡献而获得多项奖项。Burrows 博士的研究获得了两项 ACS 奖项的认可：Cope Scholar Award 和 James Flack Norris 物理有机化学奖。In 2014, she was elected to the National Academy of Sciences. 她还获得了犹他大学的罗森布拉特卓越奖，以及罗伯特帕里教学奖和杰出教学奖，以表彰她非凡的指导。她还是各种审查小组和编辑委员会的成员。她曾担任副主编 Burrows 因其在 DNA 损伤领域的杰出和开创性贡献而获得多项奖项。Burrows 博士的研究获得了两项 ACS 奖项的认可：Cope Scholar Award 和 James Flack Norris 物理有机化学奖。In 2014, she was elected to the National Academy of Sciences. 她还获得了犹他大学的罗森布拉特卓越奖，以及罗伯特帕里教学奖和杰出教学奖，以表彰她非凡的指导。她还是各种审查小组和编辑委员会的成员。她曾担任副主编 Burrows 因其在 DNA 损伤领域的杰出和开创性贡献而获得多项奖项。Burrows 博士的研究获得了两项 ACS 奖项的认可：Cope Scholar Award 和 James Flack Norris 物理有机化学奖。In 2014, she was elected to the National Academy of Sciences. 她还获得了犹他大学的罗森布拉特卓越奖，以及罗伯特帕里教学奖和杰出教学奖，以表彰她非凡的指导。她还是各种审查小组和编辑委员会的成员。她曾担任副主编 她被选为美国国家科学院院士。她还获得了犹他大学的罗森布拉特卓越奖，以及罗伯特帕里教学奖和杰出教学奖，以表彰她非凡的指导。她还是各种审查小组和编辑委员会的成员。她曾担任副主编 她被选为美国国家科学院院士。她还获得了犹他大学的罗森布拉特卓越奖，以及罗伯特帕里教学奖和杰出教学奖，以表彰她非凡的指导。她还是各种审查小组和编辑委员会的成员。她曾担任副主编Organic Letters以及The Journal of Organic Chemistry 的高级编辑。目前，她是Accounts of Chemical Research 的主编. 除了研究和教学奖项外，她还获得了 Linda K. Amos 杰出女性服务奖。她试图鼓励科学的多样性，并为女性树立榜样。当被问及被选为 TOXI 主题演讲者的原因时，Burrows 博士提到了大约 30 年在 DNA 损伤和修复领域的研究。她提到，我们最近对 DNA 损伤的细胞作用的理解超出了诱变，DNA 的一些化学修饰构成了细胞中的一个自然过程。鸟嘌呤的氧化是异常的，可能是诱变的，但我们不能排除这种修饰在细胞过程中的积极方面。其他事件可能是有益的，例如表观遗传修饰、5-甲基-C 和N ⁷-甲基-G（来自mRNA）。她对这次主题演讲机会感到高兴，她强调说：“作为一名科学家，我有机会分享我的重要发现。这种深刻的理解来自于我的同事和合作者的不懈努力。” Burrows 博士对解决谜题的热爱促使她在学术界从事职业。她的解谜策略包括问“为什么？” 和“什么是重要的？”。她专注于回答特定研究问题的过程的基本机制。在她看来，工业界往往缺乏灵活性，而学术界则提供了更多的自由来研究特定的兴趣领域，并允许她进行各种合作。作为一名成功的研究人员对世界做出贡献的两个方面对她来说很重要。首先是想办法解决问题。在这种情况下，她强调对化学反应和生物化学方面（例如细胞如何工作）的基本了解。这种方法对于在初级层面理解和解决长期存在的医学问题是必要的。她的第二个重要方面是培养下一代。带领他们走上正确的道路是一项巨大的责任。“我们有一个很棒的系统；新人不断来到实验室，与一群充满活力的年轻人一起学习总是一种荣幸”，Burrows 博士补充道。在讨论她最重要的研究发现时，她提到氧化碱基可以具有表观遗传功能，特别是如果发生在富含 G 的基因启动子序列中，它们会影响由碱基切除修复途径协调的基因表达。这一发现改变了我们对 8-oxo-dG 的看法，她说，这可能是她研究生涯中最重要的发现。这一结果来自她不断努力了解与细胞化学相关的鸟嘌呤氧化化学，并研究形成 G-四链体的富含 G 的序列的折叠动力学。此外，Burrows 博士的长期目标是在全基因组水平上了解氧化性 DNA 损伤的双向作用。这些实验包括模型质粒水平的氧化（使用基于细胞的分析来了解 DNA 修饰对 G 表达的影响）、改进测序方法，以及最重要的是了解各种蛋白质相互作用以及关键组分之间的编排。 DNA氧化损伤的修复机制。它还涉及确定 DNA（和 RNA）中的化学修饰与 G-四链体等结构基序之间的相互作用。当被问及哪些技能和经验对她的职业成功贡献最大时，Burrows 博士称赞她的同事、合作者、学生和博士后。她说与来自不同领域的优秀人士和专家一起工作总是很有趣。此外，她提到，作为一名科学家，拥有移动和进化的能力、不断扩展和获得新观点的能力非常重要。例如，她在攻读博士学位期间就开始研究小分子。现在正在研究生物分子。“我只是喜欢做研究”，Burrows 博士补充道。两个重大转变对她作为科学家来说是决定性的时刻：首先，她接受了物理有机化学家的培训；其次，她在 DNA 反应方面的工作以及对 HPLC 纯化、质谱、和凝胶电泳在DNA损伤领域工作。她感谢世界各地的朋友、同事和合作者在她的研究之旅中帮助她。她补充说，保持工作与生活的平衡具有挑战性：“我有三个孩子……我丈夫和我总是必须有时间表。我们俩过去都是周一到周五上班。星期六，我们有一个时间来照顾我们的孩子，这样我以前上午工作一半，而我丈夫经常下午工作。周日是家庭日！” 为了管理工作与生活的平衡，她建议先完成大事，并分享了阿姜布拉姆所著的《谁订购了这卡车粪？：迎接生活困难的鼓舞人心的故事》一书中的鼓舞人心的故事“宝石”。目前，她的日常工作包括教学、研究和会议。她为 400 名学生教授生物化学，其中涉及六个不同的讨论部分。由于 COVID-19，这是一个很大的变化，因为她需要提前做好更多准备。Burrows 博士进一步补充说，研究也在通过 Zoom 的小组会议进行。她还将大部分时间花在编辑工作和资助写作上。然而，她指出，她的学术界缺少社会方面。除了研究，她还喜欢烹饪：“我喜欢制作果酱，”她说。她还喜欢在冬天远足、骑自行车和滑雪。最后，伯罗斯博士给年轻科学家的建议：“做一个乐观主义者，享受工作！做科学并做得好可能会令人兴奋或令人沮丧。不要认为实验没有用，问为什么，把失败变成成功，并试着听听数据在说什么。也许数据想要表达一些不同的东西，并且可以为伟大的创新打开新的大门。保持聪明、坚持和灵活。跟随文献。是你的朋友。” 这篇文章还没有被其他出版物引用。