A/Prof. Sharon La Fontaine

STAFF PROFILE

Position

Associate Professor of Biomedical Science

Faculty

Faculty of Sci Eng & Built Env

Department

School of Life & Env. Sciences

Campus

Melbourne Burwood Campus

Qualifications

Graduate Certificate of Higher Education, Deakin University, 2013
Doctor of Philosophy, Monash University, 1994

Contact

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 profile

Research 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

  1. Committee Member, Victorian Branch of the  Australian Society for Medical Research (ASMR)
  2. ASMR Representative for The Victorian Premier’s Award for Health & Medical Research
  3. ASMR Subcommittee Member, Tertiary Careers Events
  4. Member Australian Society for Biochemistry & Molecular Biology (ASBMB) Institutional Representative
  5. Co-organiser, Melbourne Biometals Groups Annual Meetings

Publications

Filter by

2019

Molecular mechanisms of glutaredoxin enzymes: versatile hubs for thiol-disulfide exchange between protein thiols and glutathione

Zhiguang Xiao, Sharon La Fontaine, Ashley Bush, Anthony Wedd

(2019), Vol. 431, pp. 158-177, Journal of molecular biology, Amsterdam, The Netherlands, C1

journal

High-resolution crystal structure of the reduced Grx1 from Saccharomyces cerevisiae

Shadi Maghool, Sharon La Fontaine, Megan Maher

(2019), Vol. 75, pp. 392-396, Acta crystallographica section F: structural biology and crystallization communications, Chichester, Eng., C1

journal
2018

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

journal
2016

Comparative microarray analysis identifies commonalities in neuronal injury: evidence for oxidative stress, dysfunction of calcium signalling, and inhibition of autophagy-lysosomal pathway

Y Yap, R Llanos, S La Fontaine, M Cater, P Beart, N Cheung

(2016), Vol. 41, pp. 554-567, Neurochemical research, New York, N.Y., C1

journal

Reduced glutathione biosynthesis in Drosophila melanogaster causes neuronal defects linked to copper deficiency.

S Mercer, S La Fontaine, C Warr, R Burke

(2016), Vol. 137, pp. 360-370, Journal of neurochemistry, Chichester, Eng., C1

journal

Characterizing the molecular phenotype of an Atp7a(T985I) conditional knock in mouse model for X-linked distal hereditary motor neuropathy (dHMNX)

G Perez-Siles, A Grant, M Ellis, C Ly, A Kidambi, M Khalil, R Llanos, S La Fontaine, A Strickland, S Zchner, S Bermeo, E Neist, T Brennan-Speranza, R Takata, C Speck-Martins, J Mercer, G Nicholson, M Kennerson

(2016), pp. 981-882, Metallomics: integrated biometal science, Cambridge, Eng., C1

journal
2015

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

journal
2014

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

journal

Redox sulfur chemistry of the copper chaperone Atox1 is regulated by the enzyme glutaredoxin 1, the reduction potential of the glutathione couple GSSG/2GSH and the availability of Cu(I)

J Brose, S La Fontaine, A Wedd, Z Xiao

(2014), Vol. 6, pp. 793-808, Metallomics, Cambridge, Eng., C1

journal
2013

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

chapter

Gene expression profiling of rotenone-mediated cortical neuronal death: Evidence for inhibition of ubiquitin-proteasome system and autophagy-lysosomal pathway, and dysfunction of mitochondrial and calcium signaling

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, C1

journal

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, C1

journal

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis

J Telianidis, Y Hung, S Materia, S Fontaine

(2013), Vol. 5, Frontiers in Aging Neuroscience, C1

journal

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

journal
2012

Clusterin and COMMD1 independently regulate degradation of the mammalian copper ATPases ATP7A and ATP7B

S Materia, M Cater, L Klomp, J Mercer, S La Fontaine

(2012), Vol. 287, pp. 2485-2499, Journal of biological chemistry, Bethesda, Md., C1

journal
2011

Clusterin (Apolipoprotein J), a molecular chaperone that facilitates degradation of the copper-ATPases ATP7A and ATP7B

S Materia, M Cater, L Klomp, J Mercer, S La Fontaine

(2011), Vol. 286, pp. 10073-10083, Journal of Biological Chemistry, C1

journal

Unification of the copper(I) binding affinities of the metallo-chaperones Atx1, Atox1, and related proteins: Detection probes and affinity standards

Z Xiao, J Brose, S Schimo, S Ackland, S La Fontaine, A Wedd

(2011), Vol. 286, pp. 11047-11055, Journal of Biological Chemistry, C1

journal

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

journal
2010

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 and Cell Biology, C1

journal

Role of glutaredoxin1 and glutathione in regulating the activity of the copper-transporting P-type ATPases, ATP7A and ATP7B

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, C1

journal
2008

Intracellular copper deficiency increases amyloid-? secretion by diverse mechanisms

M Cater, K McInnes, Q Li, I Volitakis, S Fontaine, J Mercer, A Bush

(2008), Vol. 412, pp. 141-152, Biochemical Journal, C1

journal

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

journal
2007

Copper binding to the N-terminal metal-binding sites or the CPC motif is not essential for copper-induced trafficking of the human Wilson protein (ATP7B)

M Cater, S La Fontaine, J Mercer

(2007), Vol. 401, pp. 143-153, Biochemical Journal, C1

journal

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, C1

journal
2006

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, C1

journal

Copper-dependent interaction of glutaredoxin with the N termini of the copper-ATPases (ATP7A and ATP7B) defective in Menkes and Wilson diseases

C Lim, M Cater, J Mercer, S La Fontaine

(2006), Vol. 348, pp. 428-436, Biochemical and Biophysical Research Communications, C1

journal

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

journal
2005

A single PDZ domain protein interacts with the menkes copper ATPase, ATP7A: A new protein implicated in copper homeostasis

S Stephenson, D Dubach, C Lim, J Mercer, S La Fontaine

(2005), Vol. 280, pp. 33270-33279, Journal of Biological Chemistry, C1-1

journal
2004

Intracellular trafficking of the human Wilson protein: The role of the six N-terminal metal-binding sites

M Cater, J Forbes, S La Fontaine, D Cox, J Mercer

(2004), Vol. 380, pp. 805-813, Biochemical Journal, C1

journal

Copper Depletion Down-regulates Expression of the Alzheimer's Disease Amyloid-? Precursor Protein Gene

S Bellingham, D Lahiri, B Maloney, S La Fontaine, G Multhaup, J Camakaris

(2004), Vol. 279, pp. 20378-20386, Journal of Biological Chemistry, C1

journal
2003

Endosomal trafficking of the Menkes copper ATPase ATP7A is mediated by vesicles containing the Rab7 and Rab5 GTPase proteins

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

journal
2002

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

chapter

Correction of the copper transport defect of Menkes patient fibroblasts by expression of two forms of the sheep Wilson ATPase

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

journal

Copper-dependent iron assimilation pathway in the model photosynthetic eukaryote Chlamydomonas reinhardtii

S La Fontaine, J Quinn, S Nakamoto, M Dudley Page, V Ghre, J Moseley, J Kropat, S Merchant

(2002), Vol. 1, pp. 736-757, Eukaryotic Cell, C1

journal
2001

Effect of the toxic milk mutation (tx) on the function and intracellular localization of Wnd, the murine homologue of the Wilson copper ATPase

S La Fontaine, M Theophilos, S Firth, R Gould, R Parton, J Mercer

(2001), Vol. 10, pp. 361-370, Human Molecular Genetics, C1

journal

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, C1

journal

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

journal
1999

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

journal

Intracellular localization and loss of copper responsiveness of Mnk, the murine homologue of the Menkes protein, in cells from blotchy (Mo blo) and brindled (Mo br) mouse mutants

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

journal

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

chapter
1998

Correction of the copper transport defect of Menkes patient fibroblasts by expression of the Menkes and Wilson ATPases

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

journal

A C-terminal di-leucine is required for localization of the Menkes protein in the trans-Golgi network

M Petris, J Camakaris, M Greenough, S LaFontaine, J Mercer

(1998), Vol. 7, pp. 2063-2071, Human molecular genetics, Oxford, Eng., C1-1

journal
1993

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

journal

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, Prof Leigh Ackland, A/Prof Sharon La Fontaine, Prof Julian Mercer

  • 2011: $50,000

Establishment of a Flow Cytometry Facility at the Centre for Cellular and Molecular Biology, Deakin University

A/Prof Cenk Suphioglu, Prof Leigh Ackland, A/Prof Sharon La Fontaine, Prof Julian Mercer

  • 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

  • 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

  • 2016: $49,986

Supervisions

Principal Supervisor
2012

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

2007

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

Associate Supervisor
2017

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

2014

Yiwen Fang

Thesis entitled: Novel mechanism of Col10a1 nonsense-mediated mRNA decay

Doctor of Philosophy (Biol & Chem), School of Life and Environmental Sciences

2013

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

2006

Belinda Mary Hardman

Thesis entitled: Copper Transporters in the Human Placenta

Doctor of Philosophy (Biol & Chem), School of Life and Environmental Sciences

2005

Michael Cater

Thesis entitled: Mechanisms Regulating the Function of the ATP7B Copper-ATPase

Doctor of Philosophy (Biol & Chem), School of Life and Environmental Sciences