2018 Milton Safenowitz Fellowship Program for ALS Research Recipients
The Association is proud to support the development of bright, new scientists through the Milton Safenowitz Postdoctoral Fellowship. The Safenowitz family, through the Greater New York Chapter of The ALS Association, founded the award in memory of Mr. Safenowitz, who died of ALS in 1998. These awards are to encourage and facilitate promising new scientists to enter the ALS field. Fellows work with a senior mentor and receive extensive exposure to the ALS research community through meetings and presentations. After completing this fellowship, more than 76 percent of the awardees stay in ALS research and go on to establish their own laboratories where they continue to study ALS and mentor more ALS researchers along the way. The other 14 percent go on to careers in industry, non-profit, and medical writing with many still focusing on ALS.
The ALS Association makes a commitment of a maximum of $100,000 over a two-year period to postdoctoral fellows in the ALS field who have worked for 18 months or less as a fellow.
Edward Barbieri, Ph.D., University of Pennsylvania, Philadelphia, Pennsylvania
Title: Programming human chaperone systems against neurodegenerative disease
Summary: TDP-43 and FUS proteins have been shown to fold incorrectly and form aggregates in ALS. Our previous research indicated that proteins can harbor prion-like domains. A prion is an abnormal form of a protein that can transmit its misfolded shape onto normal variants of the same protein. We aim to understand how the prion-like domains enable misfolding and determine how to prevent or reverse the misfolding of these proteins and mitigate their toxicity.
Alyssa Coyne, Ph.D., Johns Hopkins University, Baltimore, Maryland
Title: Mechanistic insights into C9orf72 mediated disruptions in the nuclear pore complex
Summary: Our research is centered around the understanding of the molecular mechanisms underlying the most common form of familial ALS caused by a GGGGCC repeat expansion in the C9orf72 gene. In particular, we are focused on the nuclear pore complex, which is a gate between the two main cellular compartments (the nucleus and cytoplasm) and functions to control many essential cellular functions. Disruptions in the transport of macromolecules between the nucleus and cytoplasm (nucleocytoplasmic transport) have recently been implicated in multiple neurodegenerative diseases, including ALS. We are seeking to understand the basic biology of the nuclear pore complex and explore how alterations in the nuclear pore complex can contribute to cellular toxicity and disease pathogenesis.
Jorge Gomez-Deza, Ph.D., Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/National Institutes of Health (NIH)
Title: Optogenetic activation of the ALS-linked DLK pathway for drug discovery
Summary: We are generating an assay in which human neurons can be stressed and assayed in a high throughput manner that will be available for the community. An assay is an analytic procedure for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity of a target entity. The ultimate goal of our project is to identify a drug-responsive target that prevents neuronal death. To accomplish this, we will systematically silence (or turn-off) 21,000 genes and observe whether the neurons survive when they are subjected to stress. If we find any interesting candidates, we will test them in mouse models of ALS.
Ananya Ray-Soni, Ph.D., Massachusetts General Hospital, Boston, Massachusetts
Title: Targeting TDP-43 pathology in C9ORF72-mediated ALS.
Summary: A sequence motif (GGGGCC) abnormally repeated hundreds to thousands of times in the C9ORF72 gene was identified as the most frequent inherited cause of ALS. The presence of this expansion leads to the accumulation of five abnormal proteins called dipeptide repeat proteins. In addition, sick neurons of C9ORF72 patients are filled with “clumps” of protein (called aggregates) consisting of a protein called TDP-43, which is pathologically altered in the vast majority of people with ALS. How these TDP-43 protein aggregates form and why they harm neurons remain unknown, but their formation is linked to neuronal dysfunction and death in ALS. In this work, we propose to use a human neuronal cell model to investigate the mechanism by which C9ORF72 expansion causes TDP-43 to form toxic aggregates. Additionally, in collaboration with our industry partner, Neurimmune, we will test whether a novel class of human-derived antibodies that specifically recognize pathological TDP-43 can confer a therapeutic benefit by triggering its clearance in a mouse model of C9ORF72 disease. This synergistic collaboration has the potential to uncover new insights on the toxicity of TDP-43, especially in the context of C9ORF72 mutations, and to establish preclinical proof of concept for a novel immunotherapy for ALS patients.
Andrei Ursu, Ph.D., The Scripps Research Institute, Jupiter, Florida
Title: Alleviation of pathological mechanisms of genetically defined ALS by small molecules targeting RNA G4C2 repeat expansions
Summary: Our research is working toward identifying the best solutions to deliver safe and efficient therapeutic interventions that can be translated into actual treatments in the near future. The research will target the most common form of genetically inherited ALS, known as c9ALS, with rationally designed lead medicines. Multiple lines of evidence have shown that long stretches of hexanucleotide RNA repeat expansions trigger the pathological mechanisms of c9ALS leading to neurodegeneration. The Disney Lab has designed small molecules that can strongly interact with the disease-causing RNA of c9ALS, thus alleviating its toxic effects. We are continuing along these lines by taking an interdisciplinary approach to identifying efficient strategies to yield bioactive compounds that can slow or even stop neurodegeneration. Our aim is generating safe candidates that can be tested in animal models and ultimately provide viable treatments for people living with ALS.
