2022 Usher Syndrome Society Translational Research Grants
We are thrilled to announce the 3 selected grant recipients for our 2022 USS Translational Research Grants which are intended to support translational research on Usher syndrome in either Preclinical Research and/or Mechanism-‐based Therapeutic Development. These research projects include well-documented research collaborations across sensory modalities and across scientific disciplines. The USS has committed to date over $500,000 to fund this cutting-edge research.
We would like to thank the USH Society Scientific Advisory Committee for helping us evaluate all the submitted projects.
WESTERFIELD DRUG SCREENING
The progressive death of photoreceptor cells in the eye causes vision loss in Usher syndrome, while the death of cells in the inner ear causes hearing loss and balance problems. The goal of this study is to assemble a panel of FDA-approved and experimental drugs that target key pathways involved in cell death to test whether these drugs can be used to prevent or slow the death of vision, hearing, and balance cells for all types of Usher syndrome.
Dr. Monte Westerfield
In his lab that studies Usher syndrome, Dr. Monte Westerfield’s group showed that endoplasmic reticulum stress is the proximal cause of sensory cell death in Usher syndrome, which helped to discover the first known genetic modifier, PDZD7. Dr. Westerfield directs the Zebrafish Core of the Model Organism Screening Center for the Undiagnosed Diseases Network of the NIH. He received his AB degree in physics and biology from Princeton University and his PhD from Duke University Medical School. His postdoctoral training was completed at the Max Planck Institute in Munich, Germany and at Harvard Medical School before he joined the faculty in the Institute of Neuroscience at the University of Oregon. There, he met George Streisinger and began using zebrafish in his research. He established and currently directs ZFIN, the Zebrafish Information Network, and ZIRC, the Zebrafish International Resource Center.
Piloting Preclinical Development of Patient-Customized ASO Therapies for Usher Syndrome
The goal of this project is to develop new experimental treatments for Usher syndrome type 2A, using antisense oligonucleotides (ASOs), a promising class of drugs that can alter patterns of gene splicing/assembly. ASOs can be used to treat specific categories of USH2A mutations that are susceptible to splice correction. We will test this strategy by designing ASO drugs for two specific recurrent mutations, USH2A c.949C>A and c.4338_4339del, and testing their ability to rescue gene function in zebrafish and human cellular models. Successful completion of this project will provide a foundation for launching new interventional clinical trials for Usher Syndrome.
Dr. Gwenaëlle Géléoc
Dr.Géléoc is an Associate Professor in the Department of Otolaryngology and the Kirby Neurobiology Center at Boston Children's Hospital. The primary goals of her research is to characterize the functional and molecular development of the sensory cells in the inner ear and to use this knowledge to develop novel therapies for the treatment of hearing and balance disorders, in particular those associated with Usher syndrome. She earned a PhD in France and did post-doctoral work at University College London and Mass General Hospital.
Dr. Timothy Yu
Dr. Yu is an Associate Professor in the Division of Genetics & Genomics at Boston Children’s Hospital. Dr. Yu’s research is focused on the intersection of genomics, informatics, and neurobiology to better understand and treat rare neurologic diseases. Research efforts span the range from gene discovery for autism and other neurodevelopmental disorders to novel approaches for advancing individualized genomic medicine, including rare genetic disorders such as Usher Syndrome. A graduate of Harvard College, Dr. Yu completed MD-PhD training at UC San Francisco and neurology residency at Massachusetts General Hospital and Brigham and Women's Hospital.
Rescuing The Common Deep Intronic USH2A Variant c.7595- 2144A>G by innovative EDCas9 Genome Editing
Usher syndrome is characterized by hereditary deafness and subsequent blindness. Different forms of Usher syndrome are caused by different mutations in various genes, one of which is the USH2A gene. A deep intronic mutation (c.7595-2144A>G) in this gene is found in up to 4% of Usher syndrome patients. It is known to result in incorrect messenger RNA and consequently no functional protein can be formed. Within this project, we want to rescue this mutation by genome editing applying a novel bioengineered gene scissor (CRISPR/EDCas9) to restore correct RNA maturation which will lead to rescue of correct protein synthesis, hereby reverting the Usher syndrome cellular disease phenotype.
Dr. Susanne Kohl
Dr. Kohl studied Biology at the University of Tübingen and received her diploma in Human Genetics, Zoophysiology and Biochemistry in 1996 and her PhD in 2000. During her PhD, she identified the first gene for Achromatopsia and over the years described all other genes that are causative for this rare disease. Dr. Kohl has authored over 160 peer-reviewed manuscripts and is actively involved in grant and manuscript reviews. She has spent her entire scientific career at the University Eye Hospital and Institute for Ophthalmic Research in Tübingen, and her research focuses on the molecular genetics and functional analysis of genes and proteins involved in inherited retinal diseases (IRD). Her personal goal is to provide a genetic diagnosis to each individual IRD patient, thereby confirming the clinical diagnosis, providing information on inheritance and recurrence risk, and enabling patients to participate in natural history studies and clinical trials, and ultimately to receive gene- or mutation-specific therapy.
Mr. Pietro De Angeli
Mr. De Angeli received his master’s degree in Molecular Biotechnology at the University of Urbino, defending a thesis on “High-throughput mutational profiling of Cas9 endonucleases”. As a part of the European training network StarT, he has conducted his Ph.D. research at the Centre for Ophthalmology, University Hospital Tübingen, focusing on the establishment of “CRISPR/Cas9-based strategies to rescue deep-intronic variants in ABCA4”. His long-term scientific goal is to bring safe and effective therapies to patients with IRDs, therefore, he is now committed to investigate innovative genome editing approaches allowing permanent correction of genetic defects for Usher syndrome and Retinitis pigmentosa.
About the Scientific Advisory Committee (SAC)
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