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Alexandra Newton

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Alexandra C. Newton
Born
Cape Town, South Africa
Alma materStanford University (PhD)
AwardsJulius Axelrod Award in Pharmacology, ASPET (2019), Biophysics of Health and Disease Biophysical Society (2020)
Scientific career
Fields
Institutions
Thesis 'Intermembrane Protein Transfer'
Websitehttp://newtonlab.ucsd.edu

Alexandra C. Newton is Distinguished Professor of pharmacology at the University of California, San Diego.[1] Newton runs a multidisciplinary Protein kinase C and Cell signaling biochemistry and cell biology research group in the School of Medicine,[2] investigating molecular mechanisms of signal transduction in the Phospholipase C (PLC) and Phosphoinositide 3-kinase (PI3 kinase, or PI3-K) signaling pathways.[3] She has been continuously funded by the US National Institutes of Health since 1988.

Early life and education

Newton was born in Cape Town, South Africa, and was schooled in Vancouver, Athens, and Aix-en-Provence. She graduated in 1980 from the Simon Fraser University in Canada, where she was awarded a 1st-class honours degree in biochemistry and French literature.[4] She received her PhD in Chemistry in 1986 from Stanford University, working with Wray H. Huestis [5] on a thesis examining band 3, a red cell membrane protein.[6][7]

Career

Following her PhD defense, Newton took up a postdoctoral research position at University of California, Berkeley in the laboratory of Daniel E. Koshland Jr. between 1986 and 1988, and subsequently began her own independent research laboratory in 1988, as assistant professor in Chemistry at Indiana University, subsequently receiving tenure as associate professor in 1994. She moved to University of California, San Diego in 1995, first as associate professor in pharmacology and then Professor, from 2001–2017. Between 2002 and 2006, she was Vice-chair, then Chair, of the Biomedical Sciences Graduate Program before becoming the Director of the Molecular Pharmacology Track in the Biomedical Sciences Graduate Program at the University of California San Diego. She was conferred with the title of Distinguished Professor of Pharmacology in 2017. As of 2020, she is president-elect for the International Union of Biochemistry and Molecular Biology, having served, since 2016, as ASBMB representative to the IUBMB general assembly, and, since 2015, as a Member of the International Union of Biochemistry and Molecular Biology Executive Committee for Congresses and Conferences.[8] Newton has supervised, and graduated, more 25 PhD postgraduate students and trained 23 Postdoctoral Fellows.[9]

Research

Newton has been a major driver in the PKC research field since the 1980s, working originally with Daniel E. Koshland Jr. [10][11]  She helped define the multiple different mechanisms of PKC regulation by phosphorylation and its interaction with specific membrane phospholipids, such as phosphatidylserine [12][13][14][15] She has also made important discoveries in the protein phosphatase field, discovering and naming PHLPP (PH domain and Leucine rich repeat Protein Phosphatases), which regulate intracellular signaling through dephosphorylation of AKT.[16][17][18]

As of 2020, Newton has published over 190 peer-reviewed research articles that have been cited more than 25,000 times,[19] been awarded 1 patent [20] and co-edited two books on protein biochemistry and PKC.[21][22] Her work straddles basic research and has illuminated understanding of PKC in Alzheimer's disease[23][24] and as a tumor suppressor in human cancers [25]

Editorials, research honours, scientific service and outreach

Newton was a member of the Editorial Board of the Journal of Biological Chemistry between 1995–2000, an associate editor of Molecular Pharmacology (2000-2003) and since 1990, has been an expert reviewer for the National Science Foundation and Medical Research Council of Canada. She has been chair, or co-chair, for multiple committees of the American Society for Biochemistry and Molecular Biology.[26]

References

  1. ^ "PKC Signaling Laboratory - University of California, San Diego".{{cite web}}: CS1 maint: url-status (link)
  2. ^ "Health Sciences International – University of California, San Diego".
  3. ^ "PKC Signaling Laboratory - University of California, San Diego".{{cite web}}: CS1 maint: url-status (link)
  4. ^ "Inspiring Alumna, Simon Fraser University".
  5. ^ "Professor Wray Huestis Laboratory - University of California, Stanford".
  6. ^ Newton AC, Cook SL, Huestis WH (1983). "Transfer of band 3, the erythrocyte anion transporter, between phospholipid vesicles and cells". Biochemistry. 22 (26): 6110–6117. doi:10.1021/bi00295a011. PMID 6661430.
  7. ^ Huestis WH, Newton AC (1986). "Transfer of band 3, the erythrocyte anion transporter, between phospholipid vesicles and cells". Journal of Biological Chemistry. 261 (34): 16274–16278. doi:10.1016/S0021-9258(18)66712-2. PMID 3782118.
  8. ^ "International Union of Biochemistry and Molecular Biology". Archived from the original on 2019-03-24. Retrieved 2020-04-01.
  9. ^ "PhD awards".{{cite web}}: CS1 maint: url-status (link)
  10. ^ Newton A, Koshland DE (1987). "Protein Kinase C Autophosphorylates by an Intrapeptide Reaction". Journal of Biological Chemistry. 262 (21): 10185–10188. doi:10.1016/S0021-9258(18)61095-6. PMID 3611058.
  11. ^ Newton A, Koshland DE (1989). "High cooperativity, specificity, and multiplicity in the protein kinase C-lipd interaction". Journal of Biological Chemistry. 264 (25): 14909–14915. doi:10.1016/S0021-9258(18)63788-3. PMID 2768246.
  12. ^ Orr JW, Keranen LM, Newton AC (1992). "Reversible exposure of the pseudosubstrate domain of protein kinase C by phosphatidylserine and diacylglycerol". Journal of Biological Chemistry. 267 (22): 15263–15266. doi:10.1016/S0021-9258(19)49525-2. PMID 1639770.
  13. ^ Orr JW, Newton AC (1992). "Interaction of protein kinase C with phosphatidylserine. 1. Cooperativity in lipid binding". Biochemistry. 31 (19): 4661–4667. doi:10.1021/bi00134a018. PMID 1581316.
  14. ^ Orr JW, Newton AC (1992). "Interaction of protein kinase C with phosphatidylserine. 2. Specificity and regulation". Biochemistry. 31 (19): 4667–4673. doi:10.1021/bi00134a019. PMID 1581317.
  15. ^ Orr JW, Newton A (1994). "Requirement for negative charge on "activation loop" of protein kinase C." Journal of Biological Chemistry. 269 (44): 27715–27718. doi:10.1016/S0021-9258(18)47044-5. PMID 7961692.
  16. ^ Gao T, Furnari F, Newton AC (2005). "PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth". Molecular Cell. 18 (1): 13–24. doi:10.1016/j.molcel.2005.03.008. PMID 15808505.
  17. ^ Baffi TR, Van AN, Zhao W, Mills GB, Newton AC (2019). "Protein Kinase C Quality Control by Phosphatase PHLPP1 Unveils Loss-of-Function Mechanism in Cancer". Molecular Cell. 74 (2): 378–392. doi:10.1016/j.molcel.2019.02.018. PMC 6504549. PMID 30904392.
  18. ^ Grzechnik AT, Newton AC (2019). "PHLPPing through history: a decade in the life of PHLPP phosphatases". Biochemical Society Transactions. 44 (6): 1675–1682. doi:10.1042/BST20160170. PMC 5783572. PMID 27913677.
  19. ^ "Alexandra Newton Google Scholar – University of California, San Diego".
  20. ^ Violin JD, Newton AC, Tsien RJ, Zhang J (2004), Chimeric phosphorylation indicator: US Patent No. 8,669,074
  21. ^ Malacinski GM, Frielder D (1993). "Chapter 4: Essentials of Molecular Biology: The physical structure of protein molecules". Jones & Bartlett Publishers,Boston: 335. ISBN 978-0-8672-0137-6.
  22. ^ Newton AC (2003). "Methods in Molecular Biology 233: Protein Kinase C Protocols". Humana Press: 584. ISBN 978-1-59259-397-2.
  23. ^ Callender JA, Yang Y, Lordén G, Stephenson NL, Jones AC, Brognard J, Newton AC (2018). "Protein kinase Cα gain-of-function variant in Alzheimer's disease displays enhanced catalysis by a mechanism that evades down-regulation". PNAS. 115 (24): 5497–5505. doi:10.1073/pnas.1805046115. PMC 6004447. PMID 29844158.
  24. ^ "Podcast: PKCalpha in Alzheimer's disease - Science Signaling".
  25. ^ Antal CE, Hudson AM, Kang E, Zanca C, Wirth C, Stephenson NL, Trotter EW, Gallegos LL, Miller CJ, Furnari FB, Hunter T, Brognard J, Newton AC (2015). "Protein kinase Cα gain-of-function variant in Alzheimer's disease displays enhanced catalysis by a mechanism that evades down-regulation". Cell. 160 (3): 489–502. doi:10.1016/j.cell.2015.01.001. PMC 4313737. PMID 25619690.
  26. ^ "Lipid Division Spotlight - ASBMB".{{cite web}}: CS1 maint: url-status (link)
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