Jean Vance

{{short description|British-Canadian biochemist}}

{{Use dmy dates|date=April 2022}}

{{BLP primary sources|date=June 2019}}

{{Infobox scientist

| honorific_prefix = Professor

| name = Jean E. Vance

| honorific_suffix = Ph.D., F.R.S.C.

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| caption = Jean Vance in 2017

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| birth_place = Glasgow, Scotland

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| citizenship = British and Canadian

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| workplaces = University of Alberta
University of British Columbia
University of California, San Diego
University of Pittsburgh

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| doctoral_advisor = Ronald Bentley, University of Pittsburgh

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| awards = Fellow of the Royal Society of Canada


Wilhelm Bernhard International Lifetime Achievement Prize, EMBO (2018)

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| partner = Dennis E. Vance

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Jean Vance is a British-Canadian biochemist. She is known for her pioneering{{Cite journal|last1=Bayer|first1=Emmanuelle M.|last2=Calì|first2=Tito|last3=Giordano|first3=Francesca|last4=Hamacher-Brady|first4=Anne|last5=Pellegrini|first5=Luca|date=2019|title=EMBO Workshop: Membrane Contact Sites in Health and Disease|journal=Contact|language=en|volume=2|pages=251525641982593|doi=10.1177/2515256419825931|pmid=31157321|pmc=6544536|issn=2515-2564}} work on subcellular organelles and for her discovery of a connection between the endoplasmic reticulum and the mitochondrial membrane.{{Cite web|url=https://www.ualberta.ca/biochemistry/groups/mcbl/faculty-members/jean-vance/|title=Jean Vance {{!}} Faculty of Medicine & Dentistry|website=www.ualberta.ca|access-date=2019-06-12|archive-date=26 March 2019|archive-url=https://web.archive.org/web/20190326030209/https://www.ualberta.ca/biochemistry/groups/mcbl/faculty-members/jean-vance|url-status=dead}} She is a Professor of Medicine at the University of Alberta, Canada and a Fellow of the Royal Society of Canada.

Education

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.{{Cite journal|last=Vance|first=Dennis E.|date=2017-10-20|title=From masochistic enzymology to mechanistic physiology and disease|journal=The Journal of Biological Chemistry|volume=292|issue=42|pages=17169–17177|doi=10.1074/jbc.X117.815100|issn=0021-9258|pmc=5655497|pmid=28855256|doi-access=free }} She performed postdoctoral work at the University of Pittsburgh and the University of California, San Diego.

Career

After working at the University of British Columbia as a Lecturer, Vance joined the University of Alberta in 1987. She began to study the synthesis of the lipids that make up the subcellular membranes that divide the cell into compartments.{{Cite journal|last=Vance|first=J. E.|date=1988-11-04|title=Compartmentalization and differential labeling of phospholipids of rat liver subcellular membranes|journal=Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism|volume=963|issue=1|pages=10–20|issn=0006-3002|pmid=3140899|doi=10.1016/0005-2760(88)90332-3}} At the time, the site(s) of synthesis of lipids and the mechanisms by which they were moved around the cell were mysterious.{{Cite journal|last=Dolgin|first=Elie|date=2019-03-11|title=How secret conversations inside cells are transforming biology|journal=Nature|language=EN|volume=567|issue=7747|pages=162–164|doi=10.1038/d41586-019-00792-9|pmid=30858558|bibcode=2019Natur.567..162D |doi-access=free}} Working with a preparation of mitochondria, she made the surprising observation that rapid lipid synthesis occurred in a crude preparation containing additional membranes, but not in a highly purified mitochondrial fraction.{{Cite journal|last=Vance|first=J. E.|date=1990-05-05|title=Phospholipid synthesis in a membrane fraction associated with mitochondria|journal=The Journal of Biological Chemistry|volume=265|issue=13|pages=7248–7256|doi=10.1016/S0021-9258(19)39106-9 |issn=0021-9258|pmid=2332429|doi-access=free }} 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. Although this idea was initially greeted with skepticism, Vance was able to reconstitute the transfer of newly made lipids to mitochondria in a cell-free system.{{Cite journal|last=Vance|first=J. E.|date=1991-01-05|title=Newly made phosphatidylserine and phosphatidylethanolamine are preferentially translocated between rat liver mitochondria and endoplasmic reticulum|journal=The Journal of Biological Chemistry|volume=266|issue=1|pages=89–97|doi=10.1016/S0021-9258(18)52406-6 |issn=0021-9258|pmid=1898727|doi-access=free }} 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.{{Cite journal|last1=Rusiñol|first1=A. E.|last2=Cui|first2=Z.|last3=Chen|first3=M. H.|last4=Vance|first4=J. E.|date=1994-11-04|title=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|journal=The Journal of Biological Chemistry|volume=269|issue=44|pages=27494–27502|doi=10.1016/S0021-9258(18)47012-3 |issn=0021-9258|pmid=7961664|doi-access=free }} She proposed that the MAM might function as a "membrane bridge" between the endoplasmic reticulum and the mitochondria.{{Cite journal|last1=Shiao|first1=Y. J.|last2=Lupo|first2=G.|last3=Vance|first3=J. E.|date=1995-05-12|title=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|journal=The Journal of Biological Chemistry|volume=270|issue=19|pages=11190–11198|issn=0021-9258|pmid=7744750|doi=10.1074/jbc.270.19.11190|doi-access=free}} Although Vance's work was ahead of its time,{{Cite web|url=https://www.ualberta.ca/medicine/news/2019/january/discovery-of-cellular-structure-leads-to-advances-in-understanding-of-neurodegeneration-and-cancer|title=Discovery of cellular structure leads to advances in understanding neurodegeneration and cancer {{!}} Faculty of Medicine & Dentistry|website=www.ualberta.ca|access-date=2019-03-16}} it was rediscovered in the late 2000s when other researchers began to identify specific proteins, called tethers, that form the contact points between organelles.{{Cite journal|last1=Kornmann|first1=Benoît|last2=Currie|first2=Erin|last3=Collins|first3=Sean R.|last4=Schuldiner|first4=Maya|last5=Nunnari|first5=Jodi|last6=Weissman|first6=Jonathan S.|last7=Walter|first7=Peter|date=2009-07-24|title=An ER-mitochondria tethering complex revealed by a synthetic biology screen|journal=Science|volume=325|issue=5939|pages=477–481|doi=10.1126/science.1175088|issn=1095-9203|pmc=2933203|pmid=19556461|bibcode=2009Sci...325..477K }} 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.{{Cite journal|last1=Wiedemann|first1=Nils|last2=Meisinger|first2=Chris|last3=Pfanner|first3=Nikolaus|date=2009-07-24|title=Connecting Organelles|journal=Science|language=en|volume=325|issue=5939|pages=403–404|doi=10.1126/science.1178016|pmid=19628848|bibcode=2009Sci...325..403W |s2cid=9171403 |issn=0036-8075}}{{Cite journal|last1=Lackner|first1=Laura L.|last2=Ping|first2=Holly|last3=Graef|first3=Martin|last4=Murley|first4=Andrew|last5=Nunnari|first5=Jodi|date=2013-02-05|title=Endoplasmic reticulum-associated mitochondria-cortex tether functions in the distribution and inheritance of mitochondria|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=110|issue=6|pages=E458–467|doi=10.1073/pnas.1215232110|issn=1091-6490|pmc=3568303|pmid=23341591|doi-access=free }} Impaired contact between the endoplasmic reticulum and mitochondria has been suggested to underlie the pathology of several neurodegenerative diseases, including Alzheimer's disease.{{Cite journal|last=Pinton|first=Paolo|date=2018|title=Mitochondria-associated membranes (MAMs) and pathologies|journal=Cell Death & Disease|language=en|volume=9|issue=4|pages=413|doi=10.1038/s41419-018-0424-1|issn=2041-4889|pmc=5856760|pmid=29549303}}{{Cite journal|last=Vance|first=Jean E.|date=2014-04-04|title=MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond|journal=Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids|volume=1841|issue=4|pages=595–609|doi=10.1016/j.bbalip.2013.11.014|issn=0006-3002|pmid=24316057}} 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.

Vance has also worked on the transport of lipids and cholesterol to growing neurons.{{Cite journal|last1=de Chaves|first1=E. I.|last2=Rusiñol|first2=A. E.|last3=Vance|first3=D. E.|last4=Campenot|first4=R. B.|last5=Vance|first5=J. E.|date=1997-12-05|title=Role of lipoproteins in the delivery of lipids to axons during axonal regeneration|journal=The Journal of Biological Chemistry|volume=272|issue=49|pages=30766–30773|issn=0021-9258|pmid=9388216|doi=10.1074/jbc.272.49.30766|doi-access=free}} She discovered defects in cholesterol transport in neurons lacking the protein associated with Niemann–Pick disease type C, NPC1,{{Cite journal|last1=Karten|first1=Barbara|last2=Vance|first2=Dennis E.|last3=Campenot|first3=Robert B.|last4=Vance|first4=Jean E.|date=2002|title=Cholesterol accumulates in cell bodies, but is decreased in distal axons, of Niemann-Pick C1-deficient neurons|journal=Journal of Neurochemistry|volume=83|issue=5|pages=1154–1163|issn=0022-3042|pmid=12437586|doi=10.1046/j.1471-4159.2002.01220.x|s2cid=22730142 |doi-access=free}} and found that these defects can be addressed by treatment with cyclodextrin.{{Cite journal|last1=Peake|first1=Kyle B.|last2=Vance|first2=Jean E.|date=2012-03-16|title=Normalization of cholesterol homeostasis by 2-hydroxypropyl-β-cyclodextrin in neurons and glia from Niemann-Pick C1 (NPC1)-deficient mice|journal=The Journal of Biological Chemistry|volume=287|issue=12|pages=9290–9298|doi=10.1074/jbc.M111.326405|issn=1083-351X|pmc=3308731|pmid=22277650|doi-access=free }} She observed that growing neurons in vitro take up and use components from low-density lipoprotein and very low-density lipoprotein particles,{{Cite journal|last1=Posse De Chaves|first1=E. I.|last2=Vance|first2=D. E.|last3=Campenot|first3=R. B.|last4=Kiss|first4=R. S.|last5=Vance|first5=J. E.|date=2000-06-30|title=Uptake of lipoproteins for axonal growth of sympathetic neurons|journal=The Journal of Biological Chemistry|volume=275|issue=26|pages=19883–19890|issn=0021-9258|pmid=10867025|doi=10.1074/jbc.275.26.19883|doi-access=free}} and identified a role for lipoproteins provided by glial cells in stimulating nerve cell growth{{Cite journal|last1=Hayashi|first1=Hideki|last2=Campenot|first2=Robert B.|last3=Vance|first3=Dennis E.|last4=Vance|first4=Jean E.|date=2004-04-02|title=Glial lipoproteins stimulate axon growth of central nervous system neurons in compartmented cultures|journal=The Journal of Biological Chemistry|volume=279|issue=14|pages=14009–14015|doi=10.1074/jbc.M313828200|issn=0021-9258|pmid=14709547|doi-access=free}} and protecting neurons from apoptosis.{{Cite journal|last1=Hayashi|first1=Hideki|last2=Campenot|first2=Robert B.|last3=Vance|first3=Dennis E.|last4=Vance|first4=Jean E.|date=2007-02-21|title=Apolipoprotein E-containing lipoproteins protect neurons from apoptosis via a signaling pathway involving low-density lipoprotein receptor-related protein-1|journal=The Journal of Neuroscience |volume=27|issue=8|pages=1933–1941|doi=10.1523/JNEUROSCI.5471-06.2007|issn=1529-2401|pmid=17314289|pmc=6673537|doi-access=free}}

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

Together with her husband and collaborator Dennis E. Vance, she co-edited the advanced textbook "Biochemistry of lipids, lipoproteins and membranes"{{Cite book|title=Biochemistry of lipids, lipoproteins, and membranes|date=2008|publisher=Elsevier|others=Vance, Dennis E., Vance, Jean E.|isbn=978-0444532190|edition= 5th|location=Amsterdam|oclc=180880677}} from 1985 until the 5th edition in 2008.

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.{{Cite web|url=https://www.ualberta.ca/medicine/news/2018/june/a-trip-to-conclude-a-successful-scientific-career|title=A TRIP to conclude a successful scientific career {{!}} Faculty of Medicine & Dentistry|website=www.ualberta.ca|access-date=2019-03-16}} Their son, Russell Vance, is an investigator of the Howard Hughes Medical Institute and a faculty member at the University of California, Berkeley.{{Cite web|url=https://news.berkeley.edu/2013/05/09/howard-hughes-medical-institute-names-three-new-campus-investigators/|title=Howard Hughes Medical Institute names three new campus investigators|last=Sanders|first=Robert|date=2013-05-09|website=Berkeley News|language=en-US|access-date=2019-06-15}}

References

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