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Carolyn Bertozzi

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Carolyn Ruth Bertozzi (born October 10, 1966) is an American chemist and Nobel laureate, known for her wide-ranging work spanning both chemistry and biology. She coined the term "bioorthogonal chemistry"[2] for chemical reactions compatible with living systems. Her recent efforts include synthesis of chemical tools to study cell surface sugars called glycans and how they affect diseases such as cancer, inflammation, and viral infections like COVID-19.[3] At Stanford University, she holds the Anne T. and Robert M. Bass Professorship in the School of Humanities and Sciences.[4] Bertozzi is also an Investigator at the Howard Hughes Medical Institute (HHMI)[5] and is the former director of the Molecular Foundry, a nanoscience research center at Lawrence Berkeley National Laboratory.[6]

Carolyn Bertozzi
Bertozzi in 2022
Born
Carolyn Ruth Bertozzi

(1966-10-10) October 10, 1966 (age 58)
Boston, Massachusetts, U.S.
Education
Known forBioorthogonal chemistry
RelativesAndrea Bertozzi (sister)
Awards
Scientific career
FieldsChemistry
Institutions
ThesisSynthesis and biological activity of carbon-linked glycosides (1993)
Doctoral advisorMark D. Bednarski
Doctoral students
External videos
video icon "What the sugar coating on your cells is trying to tell you", TEDx Stanford
video icon "Carolyn R. Bertozzi Wins 2022 AAAS Lifetime Mentor Award", AAAS, 10 February 2022

She received the MacArthur "genius" award at age 33.[7] In 2010, she was the first woman to receive the prestigious Lemelson–MIT Prize faculty award. She is a member of the National Academy of Sciences (2005), the Institute of Medicine (2011), and the National Academy of Inventors (2013). In 2014, it was announced that Bertozzi would lead ACS Central Science, the American Chemical Society's first peer-reviewed open access journal, which offers all content free to the public.[8] Since 2021 she has been a member of the Accademia dei Lincei.[9] As an open lesbian in academia and science, Bertozzi has been a role model for students and colleagues.[10][11]

Bertozzi was awarded the 2022 Nobel Prize in Chemistry, jointly with Morten P. Meldal and Karl Barry Sharpless, "for the development of click chemistry and bioorthogonal chemistry".[12]

Education

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Carolyn Bertozzi received her B.A., summa cum laude, in chemistry from Harvard University, where she worked with Professor Joe Grabowski on the design and construction of a photoacoustic calorimeter.[13] Grabowski was impressed with her work and required Bertozzi to write a thesis on this project, which was submitted and Bertozzi won the Thomas T. Hoopes Undergraduate Thesis Prize with a large prize money.[14] While an undergraduate, she played in several bands, notably Bored of Education with future Rage Against the Machine guitarist Tom Morello.[15][16] After graduating from Harvard in 1988, she worked at Bell Labs with Chris Chidsey.[17]

Bertozzi completed her Ph.D. in chemistry at University of California, Berkeley in 1993 with Mark Bednarski, working on the chemical synthesis of oligosaccharide analogs.[18][19] While at Berkeley, she discovered that viruses can bind to sugars in the body.[20] The discovery led to her field of research, glycobiology. During Bertozzi's third year of graduate school, Bednarski was diagnosed with colon cancer, which resulted in him taking a leave of absence and changing his career path by enrolling in medical school. This left Bertozzi and the rest of the lab to complete their Ph.D. work with no direct supervision.[21][22]

Career and research

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After graduating from Berkeley with a Ph.D., Bertozzi was a postdoctoral fellow at University of California, San Francisco (UCSF) with Steven Rosen, where she studied the activity of endothelial oligosaccharides in promoting cell adhesion at inflammation sites.[23][24] While working with Rosen at UCSF, Bertozzi was able to modify the protein and sugar molecules in the walls of living cells so that the cells accept foreign materials such as implants.[25]

In 1996 Bertozzi became a faculty member in the UC Berkeley College of Chemistry[26] and a faculty scientist at Lawrence Berkeley National Laboratory, where she served as the director of the Molecular Foundry.[23][27] She has been an investigator with HHMI since 2000.[6] In 1999, while working with HHMI and at Berkeley, she founded the field of bioorthogonal chemistry and coined the term in 2003.[28][29][30] This new field and technique allows researchers to chemically modify molecules in living organisms and not interrupt the processes of the cell.[31] In 2015, Bertozzi moved to Stanford University to join the ChEM-H Institute.[32]

Bertozzi studies the glycobiology of underlying diseases such as cancer, inflammatory disorders such as arthritis, and infectious diseases such as tuberculosis. In particular, Bertozzi has advanced the understanding of cell surface oligosaccharides involved in cell recognition and inter-cellular communication. Bertozzi has applied the techniques of bioorthogonal chemistry to study glycocalyx, the sugars that surround the cell membrane. Her discoveries have advanced the field of biotherapeutics.[33] Her lab has also developed tools for research. One such development is creating chemical tools for studying glycans in living systems.[6] Her lab's development of nanotechnologies which probe biological systems lead to the development of a fast point-of-care tuberculosis test in 2018.[34][35] In 2017, due to her lab's discovery of linking the sugars on the surface of cancer cells and their ability to avoid the immune system defenses, she was invited to speak at Stanford's TED talk, giving a talk entitled "What the sugar coating on your cells is trying to tell you".[36]

Biotechnology startups

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In 2001, Bertozzi and Steve Rosen co-founded Thios Pharmaceuticals in Emeryville, California, the first company to target sulfation pathways.[37] Thios Pharmaceuticals dissolved in 2005.[38]

In 2008, Bertozzi founded a startup of her own: Redwood Bioscience also in Emeryville, California.[39] Redwood Bioscience is a biotechnology company that uses SMARTag, a site-specific protein modification technology that allows small drugs to attach to sites on the proteins and can be used to help fight cancers.[20][40] Redwood Bioscience was acquired by Catalent Pharma Solutions in 2014. Bertozzi remains a part of the advisory board for the biologics sector of the company.[40]

In 2014, she co-founded Enable Biosciences[28] of South San Francisco, California.[41] It focuses on biotechnologies for at-home diagnoses for type 1 diabetes, HIV, and other diseases.[28][42]

Bertozzi became a co-founder of Palleon Pharma of Waltham, Massachusetts, in 2015.[43] Palleon Pharma focuses on investigating glycoimmune checkpoint inhibitors as a potential treatment for cancer.[44]

In 2017, Bertozzi helped found InterVenn Biosciences, which uses mass spectrometry and artificial intelligence to enhance glycoproteomics for target and biomarker discovery, ovarian cancer diagnostics, and predicting the successes and failures of clinical trials.[28][45]

She co-founded Grace Science Foundation in 2018. The foundation focuses on curing NGLY1 deficiency through developing therapeutics that are efficient and inexpensive.[46]

In 2019, she co-founded both OliLux Biosciences and Lycia Therapeutics. OliLux Biosciences develops new methods for tuberculosis detection.[28][47] The founding of Lycia Therapeutics occurred when Bertozzi's group discovered lysosome-targeting chimeras (LYTACs). The new molecule class may be able to degrade some cardiovascular disease and cancer targets.[48] Lycia Therapeutics focuses on developing technology which utilizes lysosome-targeting chimeras (LYTACs).[28]

Bertozzi also previously served on the research advisory board of several pharmaceutical companies including GlaxoSmithKline, and until 2021 Eli Lilly.[49]

Publications

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Bertozzi has over 600 publications on Web of Science; the most cited are:

  • Sletten, EM; Bertozzi, CR (2009). "Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality". Angewandte Chemie International Edition in English. 48 (38): 6974–98. doi:10.1002/anie.200900942. PMC 2864149. PMID 19714693.
  • Bertozzi, Carolyn R.; Kiessling, Laura L. (2001). "Chemical Glycobiology". Science. 291 (5512): 2357–64. Bibcode:2001Sci...291.2357B. doi:10.1126/science.1059820. PMID 11269316. S2CID 9585674.
  • Saxon, Eliana; Bertozzi, Carolyn R. (2000). "Cell Surface Engineering by a Modified Staudinger Reaction". Science. 287 (5460): 2007–10. Bibcode:2000Sci...287.2007S. doi:10.1126/science.287.5460.2007. PMID 10720325. S2CID 19720277.
  • Agard, Nicholas J.; Prescher, Jennifer A.; Bertozzi, Carolyn R. (2005). "A Strain-Promoted [3 + 2] Azide−Alkyne Cycloaddition for Covalent Modification of Biomolecules in Living Systems". Journal of the American Chemical Society. 126 (46): 15046–15047. doi:10.1021/ja044996f. PMID 15547999.
  • Dube, DH; Bertozzi, CR (2005). "Glycans in cancer and inflammation—potential for therapeutics and diagnostics". Nature Reviews Drug Discovery. 4 (6): 477–88. doi:10.1038/nrd1751. PMID 15931257. S2CID 22525932.

Awards and honors

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Carolyn Bertozzi, receiving the Emanuel Merck Lectureship in 2011

Personal life

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Bertozzi grew up in Lexington, Massachusetts, the daughter of the late Norma Gloria (Berringer) and William Bertozzi.[92] Her father was of Italian descent.[93][94] Her maternal grandparents were from Nova Scotia, Canada.[14] She has two sisters, one of whom, Andrea Bertozzi, is on the mathematics faculty at the University of California, Los Angeles.[95] Her father was a physics professor at the Massachusetts Institute of Technology.[96][23]

Bertozzi and her two sisters grew up around science. Because their father was a physics professor, when asked what she and her sisters wanted to be when they grew up, the answer was unanimous: a nuclear physicist. The three girls would attend MIT camps, as their father dreamt that they would attend MIT due to a "mixture of pride and the promise of free tuition." To William's dismay, Carolyn attended Harvard instead because the school offered strengths outside of just science.[23]

Bertozzi briefly considered a career in music. In high school, she won several awards for music compositions and musical accomplishments. Her talent on the keyboard earned her offers as a music major from several university rock bands, but she felt that she was "always centered on the sciences".[23] Bertozzi is a lesbian and has been out since the late 1980s.[97]

References

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  1. ^ Prescher, Jennifer Ann (2006). Probing Glycosylation in Living Animals with Bioorthogonal Chemistries (PhD thesis). University of California, Berkeley. OCLC 892833679. ProQuest 305348554.
  2. ^ "Carolyn R. Bertozzi". HHMI.org. Retrieved February 5, 2020.
  3. ^ "Carolyn Bertozzi | Department of Chemistry". chemistry.stanford.edu. Retrieved March 16, 2022.
  4. ^ Adams, Amy. "Stanford chemist explains excitement of chemistry to students, the public". Stanford News. Retrieved July 19, 2015.
  5. ^ "Carolyn Bertozzi honored by GLBT organization". UC Berkeley News. February 27, 2007. Retrieved February 8, 2013.
  6. ^ a b c "Carolyn Bertozzi". HHMI. Archived from the original on May 16, 2013. Retrieved February 8, 2013.
  7. ^ "Carolyn Bertozzi, Organic Chemist". MacArthur Foundation. Retrieved February 3, 2015.
  8. ^ Wang, Linda. "Carolyn Bertozzi To Lead ACS Central Science | Chemical & Engineering News". cen.acs.org. Retrieved August 19, 2015.
  9. ^ "Alla lincea Carolyn Bertozzi uno dei Nobel per la Chimica 2022" [Carolyn Bertozzi one of the 2022 Nobel Prize winners in Chemistry]. www.lincei.it (in Italian). Accademia Nazionale dei Lincei. Retrieved October 7, 2022.
  10. ^ a b Cassell, Heather (February 22, 2007). "Two Bay Area gay scientists honored". Bay Area Reporter. Retrieved October 5, 2022.
  11. ^ a b "NOGLSTP to Honor Bertozzi, Gill, Mauzey, and Bannochie at 2007 Awards Ceremony in February". NOGLSTP. Retrieved February 19, 2019.
  12. ^ a b "Press release: The Nobel Prize in Chemistry 2022" (Press release). The Nobel Prize. October 5, 2022.
  13. ^ Grabowski, Joseph J.; Bertozzi, Carolyn R.; Jacobsen, John R.; Jain, Ahamindra; Marzluff, Elaine M.; Suh, Annie Y. (1992). "Fluorescence probes in biochemistry: An examination of the non-fluorescent behavior of dansylamide by photoacoustic calorimetry". Analytical Biochemistry. 207 (2): 214–26. doi:10.1016/0003-2697(92)90003-P. PMID 1481973.
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  18. ^ Bertozzi, Carolyn Ruth. Synthesis and biological activity of carbon-linked glycosides (Ph.D. thesis). University of California, Berkeley. OCLC 30660316. ProQuest 304068526.
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  30. ^ Sletten, Ellen M.; Bertozzi, Carolyn R. (September 20, 2011). "From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions". Accounts of Chemical Research. 44 (9): 666–676. doi:10.1021/ar200148z. ISSN 0001-4842. PMC 3184615. PMID 21838330.
  31. ^ Sletten, Ellen M.; Bertozzi, Carolyn R. (2009). "Bioorthogonal Chemistry: Fishing for Selectivity in a Sea of Functionality". Angewandte Chemie International Edition in English. 48 (38): 6974–6998. doi:10.1002/anie.200900942. ISSN 1433-7851. PMC 2864149. PMID 19714693.
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  33. ^ Xiao, Han; Woods, Elliot C.; Vukojicic, Petar; Bertozzi, Carolyn R. (August 22, 2016). "Precision glycocalyx editing as a strategy for cancer immunotherapy". Proceedings of the National Academy of Sciences. 113 (37): 10304–10309. Bibcode:2016PNAS..11310304X. doi:10.1073/pnas.1608069113. ISSN 0027-8424. PMC 5027407. PMID 27551071.
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  35. ^ Kamariza, Mireille; Shieh, Peyton; Ealand, Christopher S.; Peters, Julian S.; Chu, Brian; Rodriguez-Rivera, Frances P.; Babu Sait, Mohammed R.; Treuren, William V.; Martinson, Neil; Kalscheuer, Rainer; Kana, Bavesh D. (2018). "Rapid detection of Mycobacterium tuberculosis in sputum with a solvatochromic trehalose probe". Science Translational Medicine. 10 (430): eaam6310. doi:10.1126/scitranslmed.aam6310. ISSN 1946-6242. PMC 5985656. PMID 29491187.
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  37. ^ McCarthy, Alice A. (February 2004). "Thios Pharmaceuticals Targeting Sulfation Pathways" (PDF). Chemistry & Biology. 11 (2): 147–148. doi:10.1016/j.chembiol.2004.02.008. PMID 15123271.
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  48. ^ Banik, Steven; Pedram, Kayvon; Wisnovsky, Simon; Riley, Nicholas; Bertozzi, Carolyn (November 20, 2019). "Lysosome Targeting Chimeras (LYTACs) for the Degradation of Secreted and Membrane Proteins". Figshare. doi:10.26434/chemrxiv.7927061.v2. S2CID 213002729.
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