Frick Foundation for ALS Research
Frick Foundation for ALS Research
FRICK FOUNDATION FOR ALS RESEARCH
Group 1: Jochen H. Weishaupt. Ulm University, Germany "Molecular pathogenesis of ALS linked to TBK1 haploinsufficiency"

Jochen WeishauptJochen Weishaupt is both a researcher and a clinical neurologist and holds the Charcot Research Professorship for Neurodegeneration at the Ulm University, Germany. He obtained his MD degree from the University of Heidelberg, studying the biology of glutamate receptors in the groups of Hannah Monyer and Peter Seeburg at the Centre of Molecular Biology in Heidelberg. He received a combined clinical and research training and established his own research group at the University of Tübingen and the University of Göttingen from 1998 to 2011. In 2007 he became faculty member, and was the attending neurologist and coordinator of the amyotrophic lateral sclerosis (ALS) outpatient clinic in the neurology department of the University of Göttingen since 2009. Since 2012 he is holding the W3 Charcot Professorship for Neurodegeneration in Ulm, Germany and is head of the ALS research unit. He is also supervising the specialized ALS outpatient clinic in Ulm. His group studies the molecular mechanisms of ALS and Parkinson's disease, with specific emphasis on molecular genetics and epigenetics of ALS. His research topics include the role and dysregulation of methylation and microRNAs in ALS, cell biological mechanisms of prion-like disease spreading in ALS, and alterations of the innate immune system in ALS patients. Moreover, he is the principle investigator of a project aiming to identify novel ALS genes by whole exome sequencing. Employing whole exome sequence data from more than 250 familial ALS patients, an international consortium led by Jochen Weishaupt, was recently able to identify haploinsufficiency of the gene TBK1 as a cause for familial forms of ALS and the clinically and genetically related disease frontotemporal dementia. The project supported by the Frick Foundation aims to elucidate the downstream mechanisms of TBK1 mutations by mouse genetics. Jochen Weishaupt has won the Heinrich-Pette-Prize of the German Neurological Society (DGN) for his scientific contributions.

Group 2: Christopher J. Donnelly, Univ. Pittsburgh, USA. "Neurotoxic protein mislocalization initiates neural injury in C90RF72"

Christopher DonnellyChristopher Donnelly is an Assistant Professor in the Department of Neurobiology at the University of Pittsburgh School of Medicine and the Live Like Lou Center for ALS Research in the University of Pittsburgh Brain Institute. Dr. Donnelly received his Ph.D. in Molecular Biology and Genetics at the University of Delaware in 2011 under the advisement of Dr. Jeffery Twiss. Dr. Donnelly's graduate work focused on understanding the mechanisms and phenotypic consequence of mRNA localization in adult axons during regeneration. Dr. Donnelly completed his postdoctoral work with Dr. Jeffrey Rothstein at Johns Hopkins University in 2015 where he studied the molecular pathogenesis of C9ORF72 ALS using induced pluripotent stem cell neurons. During his postdoctoral studies he was awarded fellowships from the Maryland Stem Cell Foundation and Target ALS.

The goal of Dr. Donnelly's work is to understand the contribution of nuclear pore dysfunction and impaired nuclear trafficking in age-dependent neurodegeneration. Nuclear pore complexes function to prevent the passive diffusion of large proteins into and out of the nuclear compartment. Protein components of the nuclear pore complex can be incredibly long-lived in post-mitotic cells and rarely turnover. Degradation of these long-lived nuclear pore proteins results in age-dependent mislocalization of nuclear and cytoplasmic proteins. Recent studies have identified nuclear pore pathology and impaired nuclear trafficking of proteins and RNAs in C9ORF72 ALS. The Donnelly lab is investigating how impaired nucleocytoplasmic transport affects nuclear and cytoplasmic protein populations and hope to identify specific proteins families that confer toxicity when mistrafficked in C9ORF72 ALS. The goal of these studies are to identify if genetic or pharmacological modulation of the nuclear transport pathway is a neuroprotective strategy to treat C9ORF72 ALS/FTD. The Donnelly also lab hopes to establish image-based pharmacodynamic markers to assess whether defects in nuclear transport contribute to disease onset in non-C9ORF72 ALS populations.