Research at University of Michigan
Grant/Funding |
|
|
Dr. William Dauer
|
In 2013, Tyler’s Hope went to great means to fund the Will Dauer Grant at the University of Michigan. Investigating the essential role of torsinB, a powerful modifier for the main cause of twisting movements in torsinA dysfunction, the William Dauer grant has supported future research in DYT1 dystonia.
|
|
Cerebellothalamic Hypothesis - Dr. William Dauer
|
According to previous research, carriers of the DYT1 dystonia mutation exhibit abnormalities in the cerebellothalamocortical motor pathways. When analyzing the pathways of knock-in mice, studies showed abnormal pathways in the brainstem regions linking cerebellar and basal ganglia motor circuits. Even mice lacking abnormal motor functions showed similar abnormalities in the cerebellothalamocortical pathways. These findings link a selective brain circuit abnormality to gene carrier status and demonstrate the similar effect of DYT1 mutatnt torsion A on humans and mice.
|
After crossing mice expressing the Cre recombinase under the hindbrain driver (En1) with the inducible knock-in mouse model, results showed a selectively expressed DYT1 genotype in the hindbrain and normal torsin A gene in the forebrain structures. Conducting further analysis for an overt motor behavior phenotype, researchers concluded selectively expressing the DYT1 genotype in the hindbrain structures does not recapitulate the disease manifesting state. In the near future, Dauer and his team plan to continue their preliminary studies and explore the potential unique effects that result from torsin A dysfunction in forebrain versus hindbrain structures. Using the mice neurons, researchersi n addition hope to build a cell-culture of DYT1 dystonia.
|
|
Unraveling Torsin A function and Dysfunction - Dr. William Dauer (Stanley Fahn Grant Award)
|
Funded by the Stanley Fahn Grant Award, William Dauer and his research team studied the effects of DYT1 mutations on torsion A function. After using DYT1 mouse models to study dystonic symptoms, researchers were able to link early on set dystonia to specific changes in the early stage of brain development. With further investigation, Dauer and his team predicted the lack of a torsion duirng a critical "window" of time could be responsible for the apoptosis of cells in particular regions of the brain controlling movement.
|