2015 Milton Safenowitz Fellowship Program for ALS Research Recipients
The Association is proud to support the development of bright, young 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 young 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, approximately 90 percent of the awardees stay in ALS research. They go on to establish their own laboratories to continue studying ALS and mentor more ALS researchers along the way.
Antonia Dominguez, Ph.D., Stanford University, Stanford, Calif.
*Funding is made possible by the generous support of Phi Delta Theta.
Title: Functional analysis of C9orf72 mutations in ALS via targeted genome engineering
Summary: Dr. Dominguez uses a genome engineering approach, called CRISPR/dCas9, to regulate gene expression. She and her colleagues developed an enhanced dCas9 system that is reversible, inducible and can turn levels of specific genes up or down. The goal is to use this system to upregulate and downregulate genes associated with ALS in induced pluripotent stem cells (iPSCs) derived from people living with ALS to test effects on motor neuron survival.
Read more about Dr. Dominguez’s exciting research project and get to know the person behind the science.
Fernande Freyermuth, Ph.D., Massachusetts General Hospital, Charlestown, Mass.
Title: Targeting FUS misfolding to mitigate RNA processing alterations linked to ALS
Summary: FUS mutations are one cause of familial ALS, in which the mutations trigger FUS to mislocalize from the nucleus to the surrounding cytoplasm. One aim of her study is to determine RNA profiles induced by FUS mutations in neurons. These mutant FUS RNA signatures could be used for drug screenings. She is also exploring whether Hsp104, a molecular chaperone known to disrupt protein aggregates, could be used as a therapeutic target. Lastly, she performed a drug screen using FUS localization as a readout and found several potential compound hits that require validation.
Dejun Yang, M.D., Ph.D., University of Massachusetts Medical School, Worcester, Mass.
Title: Determine the mechanisms of ALS-associated poly (GR) toxicity and screening for therapeutic drugs
Summary: It is previously shown that C9orf72 dipeptide protein product, called poly (GR)80 is toxic in a fly model of ALS. The goal of Dr. Yang’s study is to conduct a drug screen using observed defects in fly neurons caused by (GR)80 as a readout, in order to identify compounds that suppress (GR)80 toxicity. These suppressor compounds could serve as potential ALS therapeutic compounds.
Marian Hruska-Plochan, Ph.D., University of Zurich, Zurich, Switzerland
Title: Deciphering the pathogenic mechanisms of C9orf72 dipeptide proteins
Summary: Dipeptide repeat proteins (products of the C9orf72 expansion mutation) are likely the main pathologic agent in C9orf72 ALS and FTD. The goal of Dr. Hruska-Plochan’s project is to study and compare the effects of each type of dipeptide repeat protein on function and survival of human neurons and glia (support cells of the central nervous system). Studies are ongoing to establish the models system used to answer these questions.
Tao Sun, Ph.D., Stanford University, Stanford, Calif.
Title: Genome wide identification of RNA editing dysregulation and upstream regulators in ALS
Summary: RNA editing is a process where cells make distinct changes in RNA that may include insertions, deletions and base changes in a RNA molecule. Dr. Sun’s study focuses on RNA editing at a specific neuron synapse, which can cause neuron damage if disrupted. The goal of his study is to systematically map dysregulated RNA editing sites in people living with ALS. Once identified, he wants to try to fix these editing sites using gene editing technology. RNA editing sites that affect motor neuron viability may serve as a potential ALS biomarker.
Kaspar Roet, Ph.D., Boston Children’s Hospital/Harvard Medical School/Harvard Stem Cell Institute, Boston, Mass.
Title: Which potassium channel drives ALS motor neuron hyperexcitability?
Summary: Previous studies have shown that motor neuron hyperexcitability (neurons that fire too many signals) is a common phenomenon seen in several forms of familial ALS and it leads to motor neuron death. This can be rescued by using a drug called retigabine, which is now in clinical trials to treat ALS. The goal of his study is to identify which potassium channel is responsible for the hyperexcitability, because such a channel can be a target for future therapies. Studies are ongoing and a potential candidate is currently being validated.
David Medina, Ph.D., Barrow Neurological lnstitute, Phoenix, Ariz.
Title: Modulating retinoid signaling as a therapeutic approach for ALS
Summary: Retinoic acid (RA) signaling is important for adult brain health and altered signaling has resulted in several neurodegenerative disorders, including ALS. Alternatively, upregulation of retinoic acid receptor, RARβ was shown to be neuroprotective. The goal of Dr. Medina’s study is to target the delivery of RARβ to the central nervous system to understand whether RARβ can reduce ALS pathology in ALS mouse models. Studies are ongoing to optimize delivery methods and measure preliminary results.
Jone Lopez-Erauskin, Ph.D., Ludwig Institute for Cancer Research, University of California San Diego, La Jolla, Calif.
Title: Identify key molecular targets to counteract muscle denervation in ALS.
Summary: Muscle denervation (disconnection of the muscle from the neuron) is common in both familial and sporadic ALS, which precedes motor neuron degeneration. The goal of Dr. Lopez-Erauskin’s study is to identify small molecules that promote muscle to neuron innervation/reinnervation in ALS models. To conduct her studies, she developed novel in vitro systems to perform drug screens and preliminary studies are ongoing.
