X-linked retinoschisis (XLRS) is an inherited, monogenetic ocular disease caused by mutations in the retinoschisin (RS1) gene, resulting in the development of cystic cavities throughout the retina and leading to juvenile macular degeneration. Approximately 1:15,000 males in the US are affected, classifying the condition as an orphan indication.
Human leukocyte antigen (HLA) LOH (LOH) is a known resistance mechanism by which cancers evade T cell receptor-(TCR-)based immunotherapies. This class of therapies includes immune checkpoint inhibition (ICI, e.g., Pembrolizumab), engineered TCR (T cell receptor)-T cell adoptive transfer, tumor infiltrating lymphocytes (TIL), T-cell engagers, and other modalities. Dozens of therapies in this category were developed with many in clinical trials. The resistance mechanism noted here, HLA LOH, causes these therapies to fail.
This technology includes a mouse model of TRIOBP human deafness which can be used for research and treatment development for deafness. This model contains mutations altering the TRIOP-5 isoform.
This technology includes a mouse model containing a hypothetical, previously undescribed, gene that we have proven is expressed in hair cells of the inner ear and few other tissues in the body. The hair-cell limited expression of Cre is a genetic tool for creating conditional mutations affecting hair cells almost exclusively. Hair cells are the sensory receptors of both the auditory system and the vestibular system in the ears of all vertebrates.
This technology includes ELISA based binding assays of p53, p63 or p73 provide possibilities to validate genome sequencing results, and allow the performance of more in-depth investigation to address scientific mechanisms, as well as to develop applications for high-throughput clinical and diagnosis usages. While quantitative p53 binding assays have been commercially developed, there is a lack of high-throughput method to detect binding activity of all three p53/p63/p73 family members, which are an important step for these transcription factors to perform their function.
This technology includes antibodies for TMC1 protein as a treatment for hearing loss. TMC1 is one of the common genes causing hereditary hearing loss. Our laboratory used synthetic peptides corresponding to the TMC1 protein to immunize rabbits. The resulting antisera were shown to bind to TMC1 protein expressed in heterologous expression systems. TMC1 protein is required for the transduction of sound into electrical impulses in inner ear sensory cells.
This technology includes an antibody that enables the identification and isolation of the protein and protein partners of Vangl2 for application by western blotting, immunoprecipitation and immunocytochemistry. Because planar cell polarity signaling disruption leads to direct or indirect pathologies including malformation of the neural tube, mental retardation, disruption of sensory functions (hearing, balance, vision), cancers (polykystic kidneys disease), or cardiac
This technology includes a viral vector for delivering gene therapy to the inner ear as a treatment for hearing loss and dizziness. We have found that AAv2.7m8 is able to infect multiple cell types in the mammalian inner ear with high efficiency.
This technology includes the use of atorvastatin, a medication to manage hypercholesterolemia, as a method to protect patients receiving cisplatin from hearing loss. Cisplatin chemotherapy is indicated in various cancer types in adults and children and is known to cause hearing loss. A patient on atorvastatin during chemotherapy is 46% less likely to acquire a significant cisplatin-induced hearing loss relative to a non-statin user. Atorvastatin is an FDA-approved medication routinely prescribed and well-tolerated clinically.
This technology includes a method to identify potentially therapeutic microRNAs in cancer, particularly squamous cell carcinoma of the head and neck (HNSCC). This approach first utilizes a large and publicly available expression dataset, which is then validated by a smaller independent dataset to determine deregulated microRNAs expression. These results are then intersected with in vitro functional anti-proliferative screening data to select for microRNAs that play a functional tumor suppressive role and likely serve as therapeutic targets.