Cappai laboratory: Alzheimer's disease, prion disease, Parkinson's disease and Traumatic Brain Injury

Research Overview

The major research interests of my group is focused on the key neurological disorders of Alzheimer's Disease, Parkinson's Disease, Motor Neuron Disease, Stroke and Traumatic Brain Injury. The group is studying the key proteins associated with these diseases with a major focus on the Amyloid Precursor Protein (APP) family, Amyloid-beta peptide and alpha-synuclein. We want to identify the critical molecular interactions and cellular pathways that cause the neuronal dysfunction / death that underpin these diseases, and to develop therapeutic approaches based on targeting these proteins and pathways. We have a strong interests in metallobiology, protein aggregation, protein-protein interactions, protein structure, neuroprotection, neuronal differentiation and neurodegeneration.

The lab has a broad set of technical expertise utilizing molecular biology, cell biology (primary cells and immortalized cell lines), animal models of disease, recombinant protein expression and purification, gene expression analysis and protein chemistry.

Objectives

  • To determine the function of the Alzheimer's disease Amyloid Precursor Protein and how APP binding molecules modulate its function and metabolism.
  • To determine the structure of the proteins and protein complexes involved in Alzheimer's and Parkinson's disease.
  • To determine the key molecular interactions and cellular pathways that are critical for neurotoxicity and pathology in Alzheimer's and Parkinson's disease.

Major Achievements

  • Identifying APP as a modulator of metal homeostasis.
  • Identifying dopamine as a modulator of α-synuclein aggregation
  • Identifying glypican-1 as a target for the APP:Cu complex.
  • Solving the structure of the N-terminal growth factor and copper binding domains of APP.
  • Identifying SorLA as a key modulator of APP processing.

Staff

Dr Giuseppe Ciccotosto, Senior Research Fellow
Ms Metta Jana, PhD Student
Mr Luan Luu, PhD Student
Ms Chaitanya Inapudi, PhD Student
CHAITANYA INAMPUDI (PHD STUDENT) Ms Phan Truong, PhD Student
Ms Andrea Tester, Research Assistant
Ms Audrey Lam, Honours student

Collaborators

Departmental

Kevin Barnham, Cyril Curtain and Tony White

University

Andrew Hill (Biochemistry)

External

National Collaborators

  • Corinna van den Heuvel, University of Adeliade.

International Collaborators

  • Gerd Multhaup, Free University, Berlin, Germany
  • Lars-Åke Fransson, Dr Katrin Mani, Lund University, Lund, Sweden
  • Olav Andersen, University of Aarhus, Aarhus, Denmark
  • K.P Mohanakumar, Indian Institute of Chemical Biology, Kolkata, India
  • Sasanka Chakrabarti, Institute of Post-Graduate Medical Education & Research, Kolkata India
  • Frédéric Mascarelli, INSERM, Centre de Recherche des Cordeliers, Paris, France
  • Fabio Falsone, Institute of Chemistry, University of Graz, Graz, Austria

Funding

  • NHMRC Program Grant
  • NHMRC Senior Research Fellowship
  • ARC Project Grant

Research Publications

See a full list of Professor Roberto Cappai's publications on PubMed.

  1. Corrigan F, Thornton E, Roisman LC, Leonard AV, Vink R, Blumbergs PC, van den Heuvel C, Cappai R. The neuroprotective activity of the amyloid precursor protein against traumatic brain injury is mediated via the heparin binding site in residues 96-110. J Neurochem 2014; 128(1): 196-204. doi: 10.1111/jnc.1239.
  2. Cappai R. Making sense of the amyloid precursor protein: its tail tells an interesting tale. J Neurochem 2014;130(3):325-7. doi: 10.1111/jnc.12707.
  3. Needham BE, Ciccotosto GD, Cappai R. Combined deletions of amyloid precursor protein and amyloid precursor-like protein 2 reveal different effects on mouse brain metal homeostasis. Metallomics 2014; 6(3): 598-603. doi: 10.1039/c3mt00358b.
  4. Cheng F, Cappai R, Lidfeldt J, Belting M, Fransson LA, Mani K. Amyloid Precursor Protein (APP)/APP-like Protein 2 (APLP2) Expression Is Required to Initiate Endosome-Nucleus-Autophagosome Trafficking of Glypican-1-derived Heparan Sulfate. J Biol Chem 2014; 289(30): 20871-20878.
  5. Vella LJ, Cappai R. Identification of a novel amyloid precursor protein processing pathway that generates secreted N-terminal fragments. FASEB J 2012; 26(7): 2930-40. doi: 10.1096/fj.11-200295
  6. Spoerri L, Vella LJ, Pham CL, Barnham KJ, Cappai R. The amyloid precursor protein copper binding domain histidine residues 149 and 151 mediate APP stability and metabolism. J Biol Chem 2012; 287(32): 26840-53. doi: 10.1074/jbc.M112.355743
  7. Lei P, Ayton S, Finkelstein DI, Spoerri L, Ciccotosto GD, Wright DK, Wong BX, Adlard PA, Cherny RA, Lam LQ, Roberts BR, Volitakis I, Egan GF, McLean CA, Cappai R, Duce JA, Bush AI. Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med 2012; 18(2): 291-5. doi: 10.1038/nm.2613.
  8. Duce JA, Tsatsanis A, Cater MA, James SA, Robb E, Wikhe K, Leong SL, Perez K, Johanssen T, Greenough MA, Cho HH, Galatis D, Moir RD, Masters CL, McLean C, Tanzi RE, Cappai R, Barnham KJ, Ciccotosto GD, Rogers JT, Bush AI. Iron-export ferroxidase activity of β-amyloid precursor protein is inhibited by zinc in Alzheimer's disease.Cell 2010; 142(6): 857-67. doi: 10.1016/j.cell.2010.08.014.

Research Projects



Faculty Research Themes

Neuroscience

School Research Themes

Biomedical Neuroscience, Molecular Mechanisms of Disease



Key Contact

For further information about this research, please contact Professor Roberto Cappai

Department / Centre

Pathology

Unit / Centre

Cappai laboratory: Alzheimer's disease, prion disease, Parkinson's disease and Traumatic Brain Injury