research
" ...biophotonics [is becoming] a field that will drive the discovery of new principles of cellular and
molecular biology." - 2004, Nature Reviews Molecular and Cellular Biology
"You can observe a lot just by watching."-Yogi Berra
Our laboratory is interested in how proteins move throughout the cell's organelles in humans. We have
successfully implemented and developed new tools to look at how proteins move within live cells. We are also
interested in the discovery of new protein-protein interactions by biochemical methods in vitro, and analysing these
interactions in living cells in vivo. We are currently focusing our research on a series of genetically inherited
neurodegenerative diseases that all have one basic biochemical defect in common: CAG DNA sequences >36
repeats in the gene's open reading frame that translate to glutamine amino acid stretches in the disease protein.
These diseases are collectively referred to as Polyglutamine expansion diseases and include SBMA, DRPLA,
HD, SCAs 1,2,3,6,7 and 17.
We are actively involved in trying to determine the normal functions of huntingtin and what the overall
biological role of huntingtin is in every living human cell, and how mutant huntingtin exactly leads to
Huntington’s disease (HD).
What goes Wrong in Patients with HD?
Although the problem seems simple: the
presence of polyglutamine tracts beyond 36
repeats , we currently do not really
understand why polyglutamine expansion in
different genes leads to different diseases, or
why only certain brain cells are affected by
mutant huntingtin for example, and not all
cells. Every cell in the body expresses
huntingtin, and huntingtin is a required protein
for normal development. We only recently have insights into what the huntingtin protein's normal function is within
cells. What we do know now as the result of our work and other labs worldwide, is that many polyglutamine disease
proteins shuttle to and from the nucleus normally, but in the disease state can be trapped in cellular compartments,
such as the nucleus. We have approached this problem historically by the study of how protein's enter and exit from
the nucleus , but are extending these studies to protein movement in the cell in general, and general cell biology.