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.
Kramer NJ, Carlomagno Y, Zhang YJ, Almeida S, Cook CN, Gendron TF, Prudencio M, Van Blitterswijk M, Belzil V, Couthouis J, Paul JW 3rd, Goodman LD, Daughrity L, Chew J, Garrett A, Pregent L, Jansen-West K, Tabassian LJ, Rademakers R, Boylan K, Graff-Radford NR, Josephs KA, Parisi JE, Knopman DS, Petersen RC, Boeve BF, Deng N, Feng Y, Cheng TH, Dickson DW, Cohen SN, Bonini NM, Link CD, Gao FB, Petrucelli L, Gitler AD. (2016) Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts. Science Aug 12;353(6300):708-12.
Saldi TK, Ash PEA, Wilson G, Gonzales P, Garrido-Lecca A, Roberts CM, Dostal V, Gendron TF, Stein LD, Blumenthal T, Petrucelli L, Link CD. (2014) TDP-1, the C. elegans ortholog of TDP-43, limits the accumulation of double-stranded RNA. EMBO J Dec 17;33(24):2947-66.