Frick Foundation for ALS Research
Frick Foundation for ALS Research
FRICK FOUNDATION FOR ALS RESEARCH
Professor Lin Guo

Dept. Biochemistry & Molecular Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA “Develop Protein Disaggregase and RNA Oligonucleotides to Mitigate Aberrant Phase Transition of FUS”

Dr. Lin Guostrong> is an Assistant Professor in the Department of Biochemistry and Molecular Biology at Thomas Jefferson University. She received her Ph.D. in Chemistry in 2011 from The University of Pennsylvania where she developed single-molecule spectroscopic methods to study protein folding and peptide-membrane interaction in Dr. Feng Gai's laboratory. In 2012, Dr. Guo joined Dr. James Shorter’s laboratory in the Department of Biochemistry and Biophysics at the Perelman School of Medicine at the University of Pennsylvania as a postdoctoral fellow. There, she developed biophysical tools to investigate the aberrant phase transition and aggregation of ALS disease proteins and discovered that nuclear-import receptors such as Kapβ2 can also function as chaperons and protein disaggregases to rapidly reverse aberrant phase transitions of RNA-binding proteins with prion-like domains, such as FUS, that aggregate in ALS patients. During her postdoctoral studies, Dr. Guo was awarded fellowships from Ellison Medical Foundation, American Federation for Aging Research, Alzheimer's Association, and Target ALS.
Dr. Guo’s current research continues to understand the molecular mechanisms underlying the aberrant phase transitions of ALS disease proteins. She aims to leverage her understanding of aberrant phase transition to develop strategies with therapeutic potential to prevent and reverse these toxic events. Specifically, through the support of the Frick Foundation, Dr. Guo will develop potentiated Kapβ2 variants with enhanced disaggregation activity against the fibrillization of ALS-causing FUS mutants. She will also develop RNA-based oligonucleotides to prevent and reverse FUS aberrant phase transition. The proposed study will provide two strategies to reverse FUS aberrant phase transition, which can potentially be developed into therapeutics for ALS. Moreover, investigation on how to potentiate Kapβ2’s function and how RNA oligonucleotides function to reverse FUS aberrant phase transition will give important insight in developing other agents to reverse this aberrant event that leads to neurotoxicity.

Professor Ke Zhang

Dept. Neuroscience, Mayo Clinic, Jacksonville, Florida, USA “Targeting poly(ADP-ribose) polymerase in C9orf72-mediated ALS”

Ke Zhang is an Assistant Professor in the Department of Neuroscience at Mayo Clinic, Florida. Dr. Zhang studied X-ray crystallography as an undergraduate student in the laboratory of Zihe Rao at Tsinghua University (Beijing) and joined the Ph.D. program at Baylor College of Medicine to continue his research in X-ray crystallography. However, he soon realized that his research interest was actually in neurogenetics and decided to pursue a career in that direction. Thus, he switched to the laboratory of Dr. Hugo Bellen, a renowned Drosophila geneticist, to accomplish the rest of his Ph.D. In the Bellen laboratory, he learned to use Drosophila as a genetic model to study the molecular mechanisms of neurodegeneration. His thesis focused on understanding how reactive oxygen species disrupt lipid metabolism in several neurodegenerative diseases caused by mitochondrial defects. After graduation, he performed his postdoctoral training in the laboratories of Drs. Jeffrey Rothstein and Thomas Lloyd at Johns Hopkins School of Medicine, during which he discovered disrupted nucleocytoplasmic transport as a key pathogenic event in C9ORF72-mediated ALS.
Currently, Dr. Zhang seeks to understand the role of aberrant liquid-liquid phase separation (LLPS), a process that can trigger protein aggregation, in ALS pathogenesis and explore its potential as a therapeutic target. The Zhang lab (http://www.kezhanglab.net) aims to identify small molecules and genes that modulate LLPS of dipeptide repeat proteins, toxic proteins implicated in C9ORF72-mediated ALS, understand their molecular mechanisms, and test their potentials as drugs/drug targets in iPS and animal models. Dr. Zhang has been awarded the Milton Safenowitz fellowship from the ALS Association and the Springboard fellowship from the Target ALS consortium.