Dr. Links background is originally in molecular genetics
and developmental biology, and his lab initially began using
the invertebrate worm Caenorhabditis elegans for classic developmental
genetic studies. In 1992, Dr. Links group initiated
a new series of experiments by transgenically engineering
C. elegans to express the human beta amyloid peptide, which
is centrally involved in the pathogenesis of Alzheimer's disease.
In this model, the beta amyloid peptide accumulates intracellularly,
forms amyloid, and results in cellular pathology. The goal
of his studies is to understand the molecular and cellular
basis of this toxicity, and to investigate how these processes
might be involved in Alzheimer's disease. Dr. Link takes advantage
of experimental tools available in C. elegans, such as forward
genetic screens, microarray-based gene expression studies,
and dsRNA-based gene inhibition, to help identify specific
genes involved in beta amyloid toxicity.
Dr. Link is currently expanding his studies to generate
additional transgenic models for other neurodegenerative diseases,
including Huntington's and ALS. There is increasing evidence
that different neurodegenerative diseases may have common
underlying mechanisms, which he hopes to address by comparative
transgenic modeling in C. elegans.
Fonte V., Dostal V., Roberts C.M., Gonzales P., Lacor P., Magrane J., Dingwell N., Fan E.Y., Silverman M.A., Stein G.H., Link C.D. (2011) A glycine zipper motif mediates the formation of toxic ?-amyloid oligomers in vitro and in vivo. Mol Neurodegener. 2011 Aug 23;6(1):61.
Ash, P.E., Zhang, Y.J., Roberts, C.M., Saldi, T., Hutter, H., Buratti, E., Petrucelli, L., Link, C.D. (2010). Neurotoxic effects of TDP-43 overexpression in C. elegans. Hum Mol Genet. 2010 Aug 15;19(16):3206-18.
Dostal, V., Roberts, C.M., Link, C.D. (2010) Genetic Mechanisms of Coffee Extract Protection in a Caenorhabditis elegans Model of ?-amyloid Peptide Toxicity. Genetics Nov;186(3):857-66.