Department of Integrative Physiology
University of Colorado Boulder
Boulder, CO 80309-0354
Dr. Link’s 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. Link’s 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.