Frick Foundation for ALS Research
Frick Foundation for ALS Research
Prof. Ross Buchan

University of Arizona, MCB Department, University of Arizona, Tucson, Arizona, USA. “Endocytic clearance of cytoplasmic TDP-43: Mechanism and role in ALS pathology”

Ross Buchan is an Assistant Professor in the Molecular and Cellular Biology department at the University of Arizona, Tucson. He obtained his PhD in the lab of Ian Stansfield at the University of Aberdeen, where he studied how tRNAs and codon usage in open reading frames impacts protein synthesis. His post-doc was in Roy Parker’s lab (currently at CU Boulder) where he studied P-bodies and stress granules, which are dynamic cytoplasmic membraneless organelles implicated in regulation of mRNA function and cellular stress responses. Dr Buchan co-discovered stress granules in yeast, helped elucidate their composition, assembly mechanisms and interaction with P-bodies during various stress conditions and discovered that stress granules can be cleared by an autophagic mechanism termed “granulophagy”, both in yeast and human cells.
Since establishing his own lab, Dr Buchan’s interest in ALS stems from the fact that TDP-43, a protein that aggregates in affected neuronal cells in 97% of all ALS patients, also localizes in stress granules. TDP-43 concentration in stress granules may facilitate TDP-43 aggregation and cellular toxicity; this is an area of current interest to the lab. Additionally, while investigating whether granulophagy could affect TDP-43 persistence in the cytoplasm, Dr Buchan’s lab surprisingly identified a new role for endocytic trafficking in the clearance of TDP-43 to the lysosome, which limits both cytoplasmic TDP-43 aggregation and toxicity. Additionally, cytoplasmic accumulation of TDP-43 impairs endocytic function, which may be an important underlying disease mechanism. Current goals are to define the mechanism by which cytoplasmic TDP-43 is trafficked to lysosomes for turnover in an endocytic manner, and how TDP-43 can impair endocytosis, using both yeast and human cell models. Evaluation of the therapeutic potential of modifying endocytic activity in various TDP-43 ALS models is also a key interest.
Dr Buchan has previously received a grant from the ALS Association.

Dr. Aaron Haeusler

Jefferson Weinberg ALS Center, Dept. Neuroscience, Jefferson University, Philadelphia, USA. “Identifying the role of hnRNP in the pathogenesis of C9orf72-linked ALS”.

Dr. Aaron Haeusler is a Principle Investigator in the Jefferson Weinberg ALS Center and Assistant Professor in the Department of Neuroscience at Jefferson University. He obtained his Ph.D. in biochemistry where he pursued a rigorous understanding of the molecular mechanisms that control gene regulation under the direction of Dr. Jason Kahn at the University of Maryland, College Park. After completing his Ph.D. studies in 2011, Dr. Haeusler joined Jiou Wang’s laboratory at Johns Hopkins University to focus his postdoctoral work on employing and developing disease models to understand the mechanistic contributions of nucleotide repeat expansion (NRE) genetic mutations in neurological and neuromuscular disorders. During his time at Johns Hopkins University, Dr. Haeusler demonstrated that the RNA transcribed from NRE mutations can play a critical role in disease progression through direct sequestration of key essential ribonucleoproteins, which he and his collaborators identified can lead to nucleolar stress and nucleocytoplasmic transport dysfunctions. Dr. Haeusler’s current research continues to examine the contribution of these and other disease-linked mechanisms caused by NRE mutations using the most prevalent genetic mutation associated with ALS and frontotemporal dementia, the C9orf72 NRE mutation. Moreover, his research comprises a careful mechanistic dissection of toxic gain-of-function or gene loss-of-function that results from NRE mutations and how these events contribute to neurodegenerative disease cascades. Specifically, through the support of the Frick Foundation, Dr. Haeusler will examine mechanisms that lead to altered RNA processing and transcriptomic profiles identified in patients, which may be largely caused by the dysregulation of hnRNP H. Furthermore, this work will investigate the relationship between hnRNP H dysregulation and the overlapping and unique transcriptomic profiles among C9orf72 NRE-linked and sporadic ALS patients that have C9orf72 NRE-like disease pathophysiology. Ultimately, Dr. Haeusler’s research will increase our understanding of pathophysiological disease mechanisms that underlie a number of neurological and neuromuscular disorders, and will reveal potential meaningful therapeutic strategies to mitigate neurodegenerative diseases such as ALS.