Biography
Following a PhD in Microbiology at Monash University, Dr La Fontaine joined Prof Julian Mercer's group at The Murdoch Institute (now the Murdoch Children’s Research Institute) where she began studying the molecular basis of mammalian copper metabolism. Here she began structure/function studies of the essential copper export proteins, ATP7A and ATP7B (copper-ATPases), soon after the genes for these proteins were cloned and at a time when knowledge of cellular and physiological copper regulatory mechanisms was in its infancy. During this period Dr La Fontaine made fundamental advances into the molecular basis of copper homeostasis, illuminating the complexities of the biochemistry and cell biology of the copper-ATPases and how defects in these proteins lead to the devastating effects seen in the genetically inherited copper deficiency and toxicity disorders, Menkes and Wilson diseases, respectively. Following 12 months in the Laboratory of Prof Sabeeha Merchant at UCLA, USA (1999-2000) where she studied copper and iron metabolism in the model photosynthetic organism, the unicellular green algae Chlamydomonas reinhardtii, Dr La Fontaine returned to Deakin University (Centre for Cellular & Molecular Biology in the School of Life & Environmental Sciences) with a prestigious NHMRC R.D. Wright Fellowship to establish a new program of research: elucidating copper protein networks for a holistic understanding of the proteins and pathways that contribute to cellular copper handling. This work led to the identification of new key molecules involved in cellular copper transport, and Dr La Fontaine’s research continues to drive fundamental advances in this field. In 2011, Dr La Fontaine took up a Teaching and Research position at Deakin University, as Senior Lecturer in Biomedical Science, and holds an Honorary appointment as Senior Research Fellow at The Florey Institute of Neuroscience and Mental Health.
Read more on Sharon's profileResearch interests
Dr La Fontaine’s research is focussed on the biology of the copper and its role in health and disease. Copper is an essential nutrient metal involved in a wide variety of physiological and pathological processes. It has become clear that copper regulatory pathways are corrupted in conditions that include neurodegenerative diseases and cancer leading to dysregulated copper levels, but the molecular basis of the link between copper and disease is still unclear. Dr La Fontaine’s research centres around understanding the biological underpinnings of how cells and organisms maintain an adequate balance of copper and how disruptions to this process lead to disease. Facilitated by an Honorary appointment as Senior Research Fellow at The Florey Institute of Neuroscience and Mental Health, Dr La Fontaine’s research focus is also moving towards understanding the pathological role of copper and its dysregulation in neurodegenerative disease (eg Alzheimer’s disease, and ATP7A-related motor neuropathy), as well as uncovering potential therapeutic opportunities by targeting key copper regulatory proteins. There is still much to be learned, but with a holistic view of the necessity and danger of copper and how this essential nutrient metal is managed and mismanaged, Dr La Fontaine’s group is ideally placed to continue to make significant contributions to this rapidly moving field.
Current Research Interests:
1. Copper regulatory proteins at the interface of copper homeostasis and redox biology.
2. The role of copper proteins in neuroprotection.
3. Elucidating the molecular components of the copper-regulated trafficking pathways of ATP7A and ATP7B.
4. Investigating the toxicity and therapeutic potential of copper nanomaterials (in collaboration with Dr Aaron Schultz, Deakin University and Prof Ralf Dringen, University of Bremen, Germany)
Affiliations
Honorary Senior Research Fellow, The Florey Institute of Neurosciences and Mental Health
Professional activities
- Committee Member, Victorian Branch of the Australian Society for Medical Research (ASMR)
- ASMR Representative for The Victorian Premier’s Award for Health & Medical Research
- ASMR Subcommittee Member, Tertiary Careers Events
- Member Australian Society for Biochemistry & Molecular Biology (ASBMB) Institutional Representative
- Co-organiser, Melbourne Biometals Groups Annual Meetings
Publications
Copper and lipid metabolism: A reciprocal relationship
B Blades, S Ayton, Y Hung, A Bush, S La Fontaine
(2021), Vol. 1865, Biochimica et Biophysica Acta - General Subjects, Netherlands, C1
G Perez-Siles, A Cutrupi, M Ellis, J Kuriakose, S La Fontaine, D Mao, M Uesugi, R Takata, C Speck-Martins, G Nicholson, M Kennerson
(2020), Vol. 13, DMM Disease Models and Mechanisms, England, C1
Shadi Maghool, Sharon La Fontaine, Blaine Roberts, Ann Kwan, Megan Maher
(2020), Vol. 10, SCIENTIFIC REPORTS, England, C1
Z Xiao, S La Fontaine, A Bush, A Wedd
(2019), Vol. 431, pp. 158-177, Journal of Molecular Biology, Netherlands, C1
High-resolution crystal structure of the reduced Grx1 from Saccharomyces cerevisiae
S Maghool, S La Fontaine, M Maher
(2019), Vol. 75, pp. 392-396, Acta Crystallographica Section F: Structural Biology Communications, United States, C1
Copper accumulation in senescent cells: Interplay between copper transporters and impaired autophagy
S Masaldan, S Clatworthy, C Gamell, Z Smith, P Francis, D Denoyer, P Meggyesy, S La Fontaine, M Cater
(2018), Vol. 16, pp. 322-331, Redox biology, Amsterdam, The Netherlands, C1
Y Yap, R Llanos, S La Fontaine, M Cater, P Beart, N Cheung
(2016), Vol. 41, pp. 554-567, Neurochemical Research, United States, C1
S Mercer, S La Fontaine, C Warr, R Burke
(2016), Vol. 137, pp. 360-370, Journal of neurochemistry, Chichester, Eng., C1
G Perez-Siles, A Grant, M Ellis, C Ly, A Kidambi, M Khalil, R Llanos, S Fontaine, A Strickland, S Züchner, S Bermeo, E Neist, T Brennan-Speranza, R Takata, C Speck-Martins, J Mercer, G Nicholson, M Kennerson
(2016), Vol. 8, pp. 981-992, Metallomics, England, C1
Targeting copper in cancer therapy: 'copper that cancer'
D Denoyer, S Masaldan, S La Fontaine, M Cater
(2015), Vol. 7, pp. 1459-1476, Metallomics, London, Eng., C1
Glutaredoxin1 protects neuronal cells from copper-induced toxicity
M Cater, S Materia, Z Xiao, K Wolyniec, S Ackland, Y Yap, N Cheung, S La Fontaine
(2014), Vol. 27, pp. 661-672, Biometals, New York, N.Y., C1
J Brose, S La Fontaine, A Wedd, Z Xiao
(2014), Vol. 6, pp. 793-808, Metallomics, Cambridge, Eng., C1
Copper transporting P-Type ATPases in the brain
S La Fontaine, J Camakaris, J Mercer
(2013), pp. 137-168, Brain diseases and metalloproteins, Boca Raton, Fla., B1-1
Y Yap, M Chen, Z Peng, J Manikandan, J Ng, R Llanos, S La Fontaine, P Beart, N Cheung
(2013), Vol. 62, pp. 653-663, Neurochemistry international, Amsterdam, The Netherlands, C1
Increasing intracellular bioavailable copper selectively targets prostate cancer cells
M Cater, H Pearson, K Wolyniec, P Klaver, M Bilandzic, B Paterson, A Bush, P Humbert, S La Fontaine, P Donnelly, Y Haupt
(2013), Vol. 8, pp. 1621-1631, ACS chemical biology, Washington, D.C., C1
Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis
J Telianidis, Y Hung, S Materia, S La Fontaine
(2013), Vol. 5, pp. 1-17, Frontiers in aging neuroscience, Lausanne, Switzerland, C1
Links between copper and cholesterol in Alzheimer's disease
Y Hung, A Bush, S La Fontaine
(2013), Vol. 4, pp. 1-18, Frontiers in physiology, Lausanne, Switzerland, C1-1
S Materia, M Cater, L Klomp, J Mercer, S La Fontaine
(2012), Vol. 287, pp. 2485-2499, Journal of biological chemistry, Bethesda, Md., C1
S Materia, M Cater, L Klomp, J Mercer, S La Fontaine
(2011), Vol. 286, pp. 10073-10083, Journal of biological chemistry, Bethesda, Md., C1
Z Xiao, J Brose, S Schimo, S Ackland, S La Fontaine, A Wedd
(2011), Vol. 286, pp. 11047-11055, Journal of biological chemistry, Bethesda, Md., C1
A potential copper-regulatory role for cytosolic expression of the DNA repair protein XRCC5
T Du, A Caragounis, S Parker, J Meyerowitz, S La Fontaine, K Kanninen, V Perreau, P Crouch, A White
(2011), Vol. 51, pp. 2060-2072, Free radical biology and medicine, Amsterdam, The Netherlands, C1
Mammalian copper-transporting P-type ATPases, ATP7A and ATP7B : emerging roles
S La Fontaine, M Ackland, J Mercer
(2010), Vol. 42, pp. 206-209, International journal of biochemistry & cell biology, Oxford, England, C1
W Singleton, K McInnes, M Cater, W Winnall, R McKirdy, Y Yu, P Taylor, B Ke, D Richardson, J Mercer, S La Fontaine
(2010), Vol. 285, pp. 27111-27121, Journal of biological chemistry, Bethesda, Md., C1
Intracellular copper deficiency increases amyloid-β; secretion by diverse mechanisms
M Cater, K McInnes, Q Li, I Volitakis, S La Fontaine, J Mercer, A Bush
(2008), Vol. 412, pp. 141-152, Biochemical journal, London, England, C1
Intracellular copper deficiency increases amyloid-beta secretion by diverse mechanisms
M Cater, K McInnes, Q Li, I Volitalis, S La Fontaine, J Mercer, A Bush
(2008), Vol. 412, pp. 141-152, Biochemical journal, London, England, C1-1
Investigating copper-regulated protein expression in Menkes fibroblasts using antibody microarrays
T Du, S La Fontaine, M Abdo, S Bellingham, M Greenough, I Volitakis, R Cherny, A Bush, P Hudson, J Camakaris, J Mercer, P Crouch, C Masters, V Perreau, A White
(2008), Vol. 8, pp. 1819-1831, Proteomics, Weinheim, Germany, C1-1
M Cater, S La Fontaine, J Mercer
(2007), Vol. 401, pp. 143-153, Biochemical journal, London, England, C1
Trafficking of the copper-ATPases, ATP7A and ATP7B: Role in copper homeostasis
S La Fontaine, J Mercer
(2007), Vol. 463, pp. 149-167, Archives of biochemistry and biophysics, Amsterdam, The Netherlands, C1
Copper-dependent interaction of dynactin subunit p62 with the N terminus of ATP7B but not ATP7A
C Lim, M Cater, J Mercer, S La Fontaine
(2006), Vol. 281, pp. 14006-14014, Journal of biological chemistry, Bethesda, Md, C1
C Lim, M Cater, J Mercer, S La Fontaine
(2006), Vol. 348, pp. 428-436, Biochemical and biophysical research communications, Amsterdam, The Netherlands, C1
ATP7B mediates vesicular sequestration of copper: insight into biliary copper excretion
M Cater, S La Fontaine, K Shield, Y Deal, J Mercer
(2006), Vol. 130, pp. 493-506, Gastroenterology, Amsterdam, Nertherlands, C1
S Stephenson, D Dubach, C Lim, J Mercer, S La Fontaine
(2005), Vol. 280, pp. 33270-33279, Journal of biological chemistry, Baltimore, Md, C1-1
M Cater, J Forbes, S La Fontaine, D Cox, J Mercer
(2004), Vol. 380, pp. 805-813, Biochemical journal, London, England, C1
S Bellingham, D Lahiri, B Maloney, S La Fontaine, G Multhaup, J Camakaris
(2004), Vol. 279, pp. 20378-20386, Journal of biological chemistry, Bethesda, Md., C1
M Pascale, S Franceschelli, O Moltedo, F Belleudi, M Torrisi, C Bucci, S La Fontaine, J Mercer, A Leone
(2003), Vol. 291, pp. 377-385, Experimental cell research, San Diego, Calif, C1
Comparative analysis of copper and iron metabolism in photosynthetic eukaryotes vs yeast and mammals
S La Fontaine, J Quinn, S Merchant
(2002), pp. 481-502, Handbook of copper pharmacology and toxicology, Totowa, N.J., B1
P Lockhart, S La Fontaine, S Firth, M Greenough, J Camakaris, J Mercer
(2002), Vol. 1588, pp. 189-194, Biochimica et biophysica acta (BBA) - molecular basis of disease, Netherlands, C1
S La Fontaine, J Quinn, S Nakamoto, M Page, V Gohre, J Moseley, J Kropat, S Merchant
(2002), Vol. 1, pp. 736-757, Eukaryotic Cell, Washington, D.C., C1
S La Fontaine, M Theophilos, S Firth, R Gould, R Parton, J Mercer
(2001), Vol. 10, pp. 361-370, Human molecular genetics, Oxford, England, C1
Functional studies on the Wilson copper P-Type ATPase and toxic milk mouse mutant
I Voskoboinik, M Greenough, S La Fontaine, J Mercer, J Camakaris
(2001), Vol. 281, pp. 966-970, Biochemical and biophysical research communications, San Diego, Calif, C1
Expression of the human Menkes ATPase in Xenopus laevis oocytes
K Bissig, S La Fontaine, J Mercer, M Solioz
(2001), Vol. 382, pp. 711-714, Biological chemistry, Berlin, Germany, C1-1
Functional analysis of the Menkes protein (MNK) expressed from a cDNA construct
S La Fontaine, S Firth, P Lockhart, H Brooks, J Camakaris, J Mercer
(1999), Vol. 448, pp. 67-82, Copper transport and its disorders: Molecular and cellular aspects, Berline, Germany, B1-1
The role of GMXCXXC metal binding sites in the copper-induced redistribution of the Menkes protein
D Strausak, S La Fontaine, J Hill, S Firth, P Lockhart, J Mercer
(1999), Vol. 274, pp. 11170-11177, Journal of Biological Chemistry, Bethesda, Md., C1-1
S La Fontaine, S Firth, P Lockhart, H Brooks, J Camakaris, J Mercer
(1999), Vol. 8, pp. 1069-1075, Human Molecular Genetics, Oxford, Eng., C1-1
S La Fontaine, S Firth, J Camakaris, A Englezou, M Theophilos, M Petris, M Howie, P Lockhart, M Greenough, H Brooks, R Reddel, J Mercer
(1998), Vol. 273, pp. 31375-31380, Journal of biological chemistry, Rockville, Md., C1-1
M Petris, J Camakaris, M Greenough, S LaFontaine, J Mercer
(1998), Vol. 7, pp. 2063-2071, Human molecular genetics, Oxford, Eng., C1-1
Detection of Dichelobacter nodosus using species-specific oligonucleotides as PCR primers
S La Fontaine, J Egerton, J Rood
(1993), Vol. 35, pp. 101-117, Veterinary microbiology, Amsterdam, The Netherlands, C1-1
Funded Projects at Deakin
Australian Competitive Grants
Protein networks mediating copper balance and their break-down in disease
A/Prof Sharon La Fontaine, Prof Julian Mercer, Prof James Camakaris, Prof Ann Hubbard
NHMRC Project Grant
- 2010: $183,578
- 2009: $180,157
- 2008: $176,340
Industry and Other Funding
Establishment of a Biosensor Facility at the Centre for Cellular and Molecular Biology (CCMB), Deakin University, Burwood.
A/Prof Cenk Suphioglu, EmPr Leigh Ackland, A/Prof Sharon La Fontaine, Prof Julian Mercer
Clive and Vera Ramaciotti Foundation - Equipment Grant
- 2011: $50,000
Establishment of a Flow Cytometry Facility at the Centre for Cellular and Molecular Biology, Deakin University
A/Prof Cenk Suphioglu, EmPr Leigh Ackland, A/Prof Sharon La Fontaine, Prof Julian Mercer
Clive and Vera Ramaciotti Foundation Grant - Research
- 2010: $30,000
Detemining Pathogenic Effects of ATP7A Mutations in Distal Motor Neuropath
A/Prof Marina Kennerson, Prof Julian Mercer, A/Prof Sharon La Fontaine
US Muscular Dystrophy Association
- 2015: $36,845
- 2014: $47,431
- 2013: $50,403
- 2012: $46,500
A novel role for ApoE, a major risk factor for Alzheimer's disease.
A/Prof Sharon La Fontaine, Dr Scott Ayton
BGRF Grant - Research - Bethlehem Griffiths Research Foundation
- 2016: $49,986
Supervisions
Stephanie Materia
Thesis entitled: Quality Control Mechanisms Regulating the Copper-transporting ATPases ATP7A and ATP7B
Doctor of Philosophy (Biol & Chem), School of Life and Environmental Sciences
Christopher Lim
Thesis entitled: Identification of Proteins that Interact with the Copper Transporter ATP7B
Doctor of Philosophy (Biol & Chem), School of Life and Environmental Sciences
Bryce Thomas Blades
Thesis entitled: A new role for apolipoprotein E in brain copper regulation
Doctor of Philosophy (Life & Env), School of Life and Environmental Sciences
Yann Yap
Thesis entitled: Deciphering the molecular signaling cascade in rotenone-mediated neuronal death
Doctor of Philosophy (Biol & Chem), School of Life and Environmental Sciences
Yiwen Fang
Thesis entitled: Novel mechanism of Col10a1 nonsense-mediated mRNA decay
Doctor of Philosophy (Biol & Chem), School of Life and Environmental Sciences
William Singleton
Thesis entitled: Glutaredoxin and Glutathione regulate the activity of ATP7A AND ATP7B
Master of Science (Biology & Chemistry), School of Life and Environmental Sciences
Belinda Mary Hardman
Thesis entitled: Copper Transporters in the Human Placenta
Doctor of Philosophy (Biol & Chem), School of Life and Environmental Sciences
Michael Cater
Thesis entitled: Mechanisms Regulating the Function of the ATP7B Copper-ATPase
Doctor of Philosophy (Biol & Chem), School of Life and Environmental Sciences