Research Themes

Our research uses cell lines, primary cells grown from people with ALS/FTD, and their brain and spinal cord tissue. Of particular interest to us are proteins that take on aberrant structures (oligomers and aggregates). We use transcriptomic and proteomic techniques including neuropathology to study the pathways by which cells recognise and respond to oligomers and aggregates. Pathways of interest include the ubiquitin-proteasome system, selective macroautophagy, and RNA processing – including splicing. Using drugs or gene manipulation to enhance the clearance of toxic proteins, or restore RNA processing, has great therapeutic potential in ALS/FTD.

Our Contributions

Causes and biological effects
– TDP-43 degradation; TDP-43 mouse; TDP-43 stress; TDP-43 targets database; TDP-43 IL-6
– FUS; TUBA4A; C9orf72 foci; PFN1; ANXA11; UBQLN2 autophagy; SPTLC1;
– Reg. pathways; serum biomarkers;

Neuropathology
– BSCB leakage versus TDP-43 pathology
– Microglial dysfunction
– Ubiquilin 2 versus TDP-43 neuropathology

Treatments
– Opinion
– Allele-specific TDP-43 siRNA
– TDP-43 mechanisms and therapeutics
– ASOs in ALS

New Zealand and MND
– Editorial
– NZ brain bank neuropathology and genetics
– NZ MND mortality rate
– NZ MND Registry

TDP-43 loss of function database

Differentially expressed genes and exon usage in various model systems.

TDP-43 loss of function database (version 2.0)

Differentially expressed genes and exon usage in various models including human brain pericytes.

ALS/FTD neuropathology

We use multiplexed immuno-fluorescence to label proteins including TDP-43, ubiquilin 2, p62, and dipeptide repeats.