William Dauer, M.D.

Assistant Professor, Neurology & Pharmacology

Columbia University, College of Physicians and Surgeons
Wtd3@columbia.edu

A feature of many genetic diseases is that mutations in widely expressed genes cause tissue-specific illness. One example is DYTl dystonia, a disease caused by an in-frame deletion (Deltagag) in the gene encoding torsinA. Dauer's lab discovered that neurons from both torsinA null and homozygous disease mutant "knockin" mice contain abnormal nuclear membranes. The membrane abnormalities develop in post-migratory embryonic neurons and subsequently worsen with further neuronal maturation, a finding evocative of the developmental dependence of DYTl dystonia. Observations demonstrate that neurons have a unique requirement for nuclear envelope (NE) localized torsinA function. The lab has isolated torsinA embryonic stem (ES) cells and demonstrated that they develop NE blebs when differentiated into neurons, but show no NE abnormality when differentiated into myocytes. This ES-based system is being used to identify the features that make neurons uniquely susceptible to torsinA loss-of-function.

Select Publications

Goodchild RE, Kim CE, Dauer WT. Loss of the dystonia-associated protein torsinA selectively disrupts the neuronal nuclear envelope.  Neuron. 2005 Dec 22;48(6):923-32.

Goodchild RE, Dauer WT. The AAA+ protein torsinA interacts with a conserved domain present in LAP1 and a novel ER protein.  J Cell Biol. 2005 Mar 14;168(6):855-62.

Kholodilov N, Yarygina O, Oo TF, Zhang H, Sulzer D, Dauer W, Burke RE. Regulation of the development of mesencephalic dopaminergic systems by the selective expression of glial cell line-derived neurotrophic factor in their targets.  J Neurosci. 2004 Mar 24;24(12):3136-46.