Events

You are here

Optogenetic Modulation of TDP-43 Proteinopathy

EVENT: 
Weekly Seminar
Who Should Attend: 
Researchers

Speakers

Guest Speaker
Christopher J. Donnelly, Ph.D.
Assistant Professor
Department of Neurobiology - Live Like Lou Center for ALS Research, Brain Institute
University of Pittsburgh - School of Medicine

Abstract:

Pathological hallmarks of age-related neurodegenerative diseases are intracellular protein inclusions. TDP-43 is a predominantly nuclear DNA/RNA binding protein but is found mislocalized to the cytoplasm and aggregated in a variety of neurodegenerative diseases. TDP-43 proteinopathy is a neuropathological feature of amyotrophic lateral sclerosis, a fatal disease characterized by the degeneration of the motor neurons of the brain and spinal cord, and a predominant pathology in frontotemporal dementia, the most common cause of dementia in individual under the age of 65. Modeling TDP-43 and other neurodegenerative proteinopathies is challenging and relies on nonphysiological overexpression of wild-type or mutant variant of the proteins. This approach lacks any control over the aggregation process. Furthermore, these models do not often mimic key features of the diseases in patients. To overcome this problem, we developed a photokinetic technique that allows for the induction of neurodegenerative protein oligomerization under spatial and temporal control. Employing this light-based/optogenetic approach, we identified the intracellular requirements for the development of TDP-43 proteinopathy and identified mechanisms to disrupt the formation of these pathological inclusions.

Christopher J. Donnelly, Ph.D. Figure

Publications

Zhang K, Donnelly CJ, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S, Gupta S, Thomas MA, Hong I, Chiu SL, Huganir RL, Ostrow LW, Matunis MJ, Wang J, Sattler R, Lloyd TE, Rothstein JD.
The C9orf72 repeat expansion disrupts nucleocytoplasmic transport.
Nature. 2015 Sep 3;525(7567):56-61. doi: 10.1038/nature14973. Epub 2015 Aug 26.
A.R. Haeusler, C.J. Donnelly, G. Periz, R. Sattler, E. A. Simko, P.G. Shaw, M. S. Kim, A. Pandry, J.D. Rothstein, J. Wang.
Structural polymorphisms of C9ORF72 hexanucleotide repeats cause ALS/FTD defects through abortive transcription and nucleolar stress.
Nature 507 (7491): 195-200.
Donnelly CJ, Zhang PW, Pham JT, Haeusler AR, Mistry NA, Vidensky S, Daley EL, Poth EM, Hoover B, Fines DM, Maragakis N, Tienari PJ, Petrucelli L, Traynor BJ, Wang J, Rigo F, Bennett CF, Blackshaw S, Sattler R, Rothstein JD.
RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention.
Neuron. 2013 Oct 16;80(2):415-28. doi: 10.1016/j.neuron.2013.10.015.

When

Tuesday, June 26, 2018 - 12:30pm

Where

785 Mamaroneck Avenue
White Plains, NY 10605
United States
Conference Room: 
Billings Building – Rosedale

More Information