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Jean Vance

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Professor
Jean E. Vance
Ph.D., F.R.S.C.
Jean Vance in 2017
Born
Glasgow, Scotland
CitizenshipBritish and Canadian
PartnerDennis E. Vance
AwardsFellow of the Royal Society of Canada
Wilhelm Bernhard International Lifetime Achievement Prize, EMBO (2018)
Scientific career
InstitutionsUniversity of Alberta
University of British Columbia
University of California, San Diego
University of Pittsburgh
Doctoral advisorRonald Bentley, University of Pittsburgh

Jean Vance is a British-Canadian biochemist. She is known for her pioneering[1][2] work on subcellular organelles and for her discovery of a connection between the endoplasmic reticulum and the mitochondrial membrane.[3] She is a Professor of Medicine at the University of Alberta, Canada and a Fellow of the Royal Society of Canada.

Education

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Vance earned her BSc in Chemistry from Bedford College, London, UK in 1964 and her Ph.D. from the University of Pittsburgh, USA in 1969, where she worked with Ronald Bentley.[4] She performed postdoctoral work at the University of Pittsburgh and the University of California, San Diego.

Career

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After working at the University of British Columbia as a Lecturer, Vance joined the University of Alberta in 1987.[4] She began to study the synthesis of the lipids that make up the subcellular membranes that divide the cell into compartments.[5] At the time, the site(s) of synthesis of lipids and the mechanisms by which they were moved around the cell were mysterious.[1] Working with a preparation of mitochondria, she made the surprising[1] observation that rapid lipid synthesis occurred in a crude preparation containing additional membranes, but not in a highly purified mitochondrial fraction.[6] This led her to hypothesize that a specialized membrane compartment, which she called Fraction X, might be responsible for the transfer of lipids from the endoplasmic reticulum to mitochondria.[6] Although this idea was initially greeted with skepticism,[1] Vance was able to reconstitute the transfer of newly made lipids to mitochondria in a cell-free system.[7] She purified "Fraction X", renaming it the mitochondria-associated membrane (MAM) fraction, and showed that it contained highly active enzymes able to synthesize a variety of membrane components.[8] She proposed that the MAM might function as a "membrane bridge" between the endoplasmic reticulum and the mitochondria.[9] Although Vance's work was ahead of its time,[10] it was rediscovered in the late 2000s when other researchers began to identify specific proteins, called tethers, that form the contact points between organelles.[1][11] The mitochondria-endoplasmic reticulum bridge Vance originally identified is now named the endoplasmic reticulum membrane protein complex and has been shown to be important in the function, positioning and inheritance of mitochondria.[12][13] Impaired contact between the endoplasmic reticulum and mitochondria has been suggested to underlie the pathology of several neurodegenerative diseases, including Alzheimer's disease.[14][15] The newly appreciated importance of contacts among different subcellular organelles led in 2018 to the founding of a journal devoted to the area, Contact, published by SAGE Publishing.[2]

Vance has also worked on the transport of lipids and cholesterol to growing neurons.[16] She discovered defects in cholesterol transport in neurons lacking the protein associated with Niemann–Pick disease type C, NPC1,[17] and found that these defects can be addressed by treatment with cyclodextrin.[18] She observed that growing neurons in vitro take up and use components from low-density lipoprotein and very low-density lipoprotein particles,[16][19] and identified a role for lipoproteins provided by glial cells in stimulating nerve cell growth[20] and protecting neurons from apoptosis.[21]

In 2018 she was awarded the Wilhelm Bernhard International Lifetime Achievement Prize by the European Molecular Biology Organization.[2][10]

Together with her husband and collaborator Dennis E. Vance, she co-edited the advanced textbook "Biochemistry of lipids, lipoproteins and membranes"[22] from 1985 until the 5th edition in 2008.[4]

Vance and her husband both elected to enrol in the University of Alberta's Transitional Retirement Program in 2017, planning to wind down their research over a three-year period.[23] Their son, Russell Vance, is an investigator of the Howard Hughes Medical Institute and a faculty member at the University of California, Berkeley.[24]

References

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  1. ^ a b c d e Dolgin, Elie (11 March 2019). "How secret conversations inside cells are transforming biology". Nature. 567 (7747): 162–164. Bibcode:2019Natur.567..162D. doi:10.1038/d41586-019-00792-9. PMID 30858558.
  2. ^ a b c Bayer, Emmanuelle M.; Calì, Tito; Giordano, Francesca; Hamacher-Brady, Anne; Pellegrini, Luca (2019). "EMBO Workshop: Membrane Contact Sites in Health and Disease". Contact. 2: 251525641982593. doi:10.1177/2515256419825931. ISSN 2515-2564. PMC 6544536. PMID 31157321.
  3. ^ "Jean Vance | Faculty of Medicine & Dentistry". www.ualberta.ca. Archived from the original on 26 March 2019. Retrieved 12 June 2019.
  4. ^ a b c Vance, Dennis E. (20 October 2017). "From masochistic enzymology to mechanistic physiology and disease". The Journal of Biological Chemistry. 292 (42): 17169–17177. doi:10.1074/jbc.X117.815100. ISSN 0021-9258. PMC 5655497. PMID 28855256.
  5. ^ Vance, J. E. (4 November 1988). "Compartmentalization and differential labeling of phospholipids of rat liver subcellular membranes". Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 963 (1): 10–20. doi:10.1016/0005-2760(88)90332-3. ISSN 0006-3002. PMID 3140899.
  6. ^ a b Vance, J. E. (5 May 1990). "Phospholipid synthesis in a membrane fraction associated with mitochondria". The Journal of Biological Chemistry. 265 (13): 7248–7256. doi:10.1016/S0021-9258(19)39106-9. ISSN 0021-9258. PMID 2332429.
  7. ^ Vance, J. E. (5 January 1991). "Newly made phosphatidylserine and phosphatidylethanolamine are preferentially translocated between rat liver mitochondria and endoplasmic reticulum". The Journal of Biological Chemistry. 266 (1): 89–97. doi:10.1016/S0021-9258(18)52406-6. ISSN 0021-9258. PMID 1898727.
  8. ^ Rusiñol, A. E.; Cui, Z.; Chen, M. H.; Vance, J. E. (4 November 1994). "A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins". The Journal of Biological Chemistry. 269 (44): 27494–27502. doi:10.1016/S0021-9258(18)47012-3. ISSN 0021-9258. PMID 7961664.
  9. ^ Shiao, Y. J.; Lupo, G.; Vance, J. E. (12 May 1995). "Evidence that phosphatidylserine is imported into mitochondria via a mitochondria-associated membrane and that the majority of mitochondrial phosphatidylethanolamine is derived from decarboxylation of phosphatidylserine". The Journal of Biological Chemistry. 270 (19): 11190–11198. doi:10.1074/jbc.270.19.11190. ISSN 0021-9258. PMID 7744750.
  10. ^ a b "Discovery of cellular structure leads to advances in understanding neurodegeneration and cancer | Faculty of Medicine & Dentistry". www.ualberta.ca. Retrieved 16 March 2019.
  11. ^ Kornmann, Benoît; Currie, Erin; Collins, Sean R.; Schuldiner, Maya; Nunnari, Jodi; Weissman, Jonathan S.; Walter, Peter (24 July 2009). "An ER-mitochondria tethering complex revealed by a synthetic biology screen". Science. 325 (5939): 477–481. Bibcode:2009Sci...325..477K. doi:10.1126/science.1175088. ISSN 1095-9203. PMC 2933203. PMID 19556461.
  12. ^ Wiedemann, Nils; Meisinger, Chris; Pfanner, Nikolaus (24 July 2009). "Connecting Organelles". Science. 325 (5939): 403–404. Bibcode:2009Sci...325..403W. doi:10.1126/science.1178016. ISSN 0036-8075. PMID 19628848. S2CID 9171403.
  13. ^ Lackner, Laura L.; Ping, Holly; Graef, Martin; Murley, Andrew; Nunnari, Jodi (5 February 2013). "Endoplasmic reticulum-associated mitochondria-cortex tether functions in the distribution and inheritance of mitochondria". Proceedings of the National Academy of Sciences of the United States of America. 110 (6): E458–467. doi:10.1073/pnas.1215232110. ISSN 1091-6490. PMC 3568303. PMID 23341591.
  14. ^ Pinton, Paolo (2018). "Mitochondria-associated membranes (MAMs) and pathologies". Cell Death & Disease. 9 (4): 413. doi:10.1038/s41419-018-0424-1. ISSN 2041-4889. PMC 5856760. PMID 29549303.
  15. ^ Vance, Jean E. (4 April 2014). "MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1841 (4): 595–609. doi:10.1016/j.bbalip.2013.11.014. ISSN 0006-3002. PMID 24316057.
  16. ^ a b de Chaves, E. I.; Rusiñol, A. E.; Vance, D. E.; Campenot, R. B.; Vance, J. E. (5 December 1997). "Role of lipoproteins in the delivery of lipids to axons during axonal regeneration". The Journal of Biological Chemistry. 272 (49): 30766–30773. doi:10.1074/jbc.272.49.30766. ISSN 0021-9258. PMID 9388216.
  17. ^ Karten, Barbara; Vance, Dennis E.; Campenot, Robert B.; Vance, Jean E. (2002). "Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons". Journal of Neurochemistry. 83 (5): 1154–1163. doi:10.1046/j.1471-4159.2002.01220.x. ISSN 0022-3042. PMID 12437586. S2CID 22730142.
  18. ^ Peake, Kyle B.; Vance, Jean E. (16 March 2012). "Normalization of cholesterol homeostasis by 2-hydroxypropyl-β-cyclodextrin in neurons and glia from Niemann-Pick C1 (NPC1)-deficient mice". The Journal of Biological Chemistry. 287 (12): 9290–9298. doi:10.1074/jbc.M111.326405. ISSN 1083-351X. PMC 3308731. PMID 22277650.
  19. ^ Posse De Chaves, E. I.; Vance, D. E.; Campenot, R. B.; Kiss, R. S.; Vance, J. E. (30 June 2000). "Uptake of lipoproteins for axonal growth of sympathetic neurons". The Journal of Biological Chemistry. 275 (26): 19883–19890. doi:10.1074/jbc.275.26.19883. ISSN 0021-9258. PMID 10867025.
  20. ^ Hayashi, Hideki; Campenot, Robert B.; Vance, Dennis E.; Vance, Jean E. (2 April 2004). "Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures". The Journal of Biological Chemistry. 279 (14): 14009–14015. doi:10.1074/jbc.M313828200. ISSN 0021-9258. PMID 14709547.
  21. ^ Hayashi, Hideki; Campenot, Robert B.; Vance, Dennis E.; Vance, Jean E. (21 February 2007). "Apolipoprotein E-containing lipoproteins protect neurons from apoptosis via a signaling pathway involving low-density lipoprotein receptor-related protein-1". The Journal of Neuroscience. 27 (8): 1933–1941. doi:10.1523/JNEUROSCI.5471-06.2007. ISSN 1529-2401. PMC 6673537. PMID 17314289.
  22. ^ Biochemistry of lipids, lipoproteins, and membranes. Vance, Dennis E., Vance, Jean E. (5th ed.). Amsterdam: Elsevier. 2008. ISBN 978-0444532190. OCLC 180880677.{{cite book}}: CS1 maint: others (link)
  23. ^ "A TRIP to conclude a successful scientific career | Faculty of Medicine & Dentistry". www.ualberta.ca. Retrieved 16 March 2019.
  24. ^ Sanders, Robert (9 May 2013). "Howard Hughes Medical Institute names three new campus investigators". Berkeley News. Retrieved 15 June 2019.
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