Project Grant K99DC021984
- This federal Project Grant award, totaling $249,000.00, was provided by the National Institute on Deafness and Other Communication Disorders (NIDCD) under the Research Related to Deafness and Communication Disorders program (CFDA 93.173). The grant supports the development of a CRISPR-based toolkit to investigate the roles of various transcription factors in the development of hair cells, the specialized sensory cells of the inner ear, using an in vitro inner ear organoid model. The project aims...
- This Project Grant award from the National Institute on Deafness and Other Communication Disorders (NIDCD), under the Research Related to Deafness and Communication Disorders program (CFDA 93.173), provides $767,494 to the University of Miami to develop human inner ear organoid platforms for studying genetic hearing loss and vestibular disorders. The key objectives are to: 1) establish and optimize human induced pluripotent stem cell-derived 3D inner ear organoid systems from patients with...
- This federal Project Grant award for $438,244 from the National Institute on Deafness and Other Communication Disorders (NIDCD), under the Research Related to Deafness and Communication Disorders (CFDA 93.173) program, supports research to investigate the role of the blood-labyrinthine barrier (BLB) in inner ear homeostasis and disease. The key objectives are to use human induced pluripotent stem cell (hiPSC) technology to model BLB-specific microvascular interactions and explore novel...
- This Project Grant award of $486,750.00 from the National Institute on Deafness and Other Communication Disorders (NIDCD), under the Research Related to Deafness and Communication Disorders (CFDA 93.173) program, will support research on the morphological changes and polarization of supporting cells in the inner ear of mice. The primary awardee, The Jackson Laboratory, will conduct this research project to investigate how mouse pillar and Deiter's cells, which are specific types of supporting...
- This $582,552 Project Grant award from the National Institute on Deafness and Other Communication Disorders (NIDCD) under the federal Research Related to Deafness and Communication Disorders program (CFDA 93.173) aims to understand the role of the protein otoferlin in auditory circuit development and how gene therapy can restore hearing in patients with congenital deafness caused by otoferlin variants. The project will investigate spontaneous neural activity patterns, auditory cortex...
- This Project Grant award from the National Institute on Deafness and Other Communication Disorders (NIDCD), under the federal Research Related to Deafness and Communication Disorders program (CFDA 93.173), aims to establish a comprehensive molecular and physiological biorepository of the human inner ear. The $445,956 award to Vanderbilt University Medical Center will support the collection of inner ear tissues, including the cochlea and vestibular apparatus, as well as non-invasive physiological...
- This $104,512 federal Project Grant from the National Institute on Deafness and Other Communication Disorders (CFDA 93.173 - Research Related to Deafness and Communication Disorders) aims to mitigate vocal fold scarring through CRISPR/Cas-9-mediated gene editing of fibroblasts. The research proposal seeks to identify gene targets that could prevent the differentiation of vocal fold fibroblasts into myofibroblasts, thereby reducing excessive fibrous protein production and cell proliferation...
- The National Institute on Deafness and Other Communication Disorders (NIDCD) awarded the University of Southern California (USC) a $456,500 Project Grant (CFDA 93.173) to develop a novel diagnostic test for sensory hearing loss. The "Gain-Sensitive Cochlear Microphonics" (GCM) test aims to assess the functional state and site of damage within the cochlear amplifier, which is crucial for hearing sensitivity and range. The proposed research will validate the GCM test in mice by comparing...
- The Department of Health and Human Services (HHS) National Institutes of Health (NIH) awarded a $1,319,060 Project Grant to Duke University under the Trans-NIH Research Support (CFDA 93.310) program. The grant, effective September 1, 2023 through August 31, 2026, will fund research to study the robust formation of organs, with a focus on the development of the semicircular canals in the inner ear of zebrafish. The research aims to measure variations in tissue patterns, investigate the respective...
- This federal Project Grant award of $652,216.00 from the National Institute on Deafness and Other Communication Disorders (NIDCD) under the Research Related to Deafness and Communication Disorders program (CFDA 93.173) supports research on epigenetic mechanisms involved in cochlear damage and repair. The principal investigator at Rutgers, The State University in New Jersey will investigate how the CHD4 chromatin-remodeling protein maintains hair cell identity in the cochlea. The project aims...
A CRISPR-BASED TOOLKIT FOR INVESTIGATING HAIR CELL TRANSCRIPTION FACTORS IN INNER EAR ORGANOIDS - PROJECT SUMMARY/ABSTRACT HAIR CELLS (HCS) ARE THE SPECIALIZED SENSORY CELLS OF THE INNER EAR THAT PLAY A CRUCIAL ROLE IN TRANSMITTING ENVIRONMENTAL INFORMATION, SUCH AS SOUND AND MOTION, TO THE BRAIN. IN ADULT MAMMALS, HCS CANNOT REGENERATE NATURALLY. THEREFORE, A LARGE EFFORT HAS BEEN MADE TO UNDERSTAND THE NORMAL DEVELOPMENT OF AUDITORY AND VESTIBULAR HCS, SO THAT EFFECTIVE REGENERATIVE THERAPIES CAN BE ESTABLISHED. TECHNOLOGICAL ADVANCEMENTS IN STUDYING TRANSCRIPTIONAL CONTROL HAVE PROVIDED VALUABLE INSIGHTS INTO THE ROLES OF DIFFERENT TRANSCRIPTION FACTORS (TFS) SUCH AS ATOH1, POU4F3, GFI1, INSM1, TBX2, AND IKZF2 IN THE DEVELOPMENT OF HCS. HOWEVER, THE APPLICATION OF CERTAIN TOOLS, SUCH AS CRISPR-MEDIATED GENE ACTIVATION AND INHIBITION, FOR STUDYING HC DEVELOPMENT HAS BEEN LIMITED BY THE COMPLICATED USE OF ANIMAL MODELS. RECENTLY, A HIGHLY SCALABLE PROTOCOL WAS DEVELOPED TO GUIDE MOUSE EMBRYONIC STEM CELLS (MESCS) TOWARDS INNER EAR SENSORY CELLS IN VITRO. OVER A SPAN OF 2-3 WEEKS, THESE INNER EAR ORGANOIDS PRODUCE SENSORY EPITHELIA-LIKE STRUCTURES COMPLETE WITH MECHANOSENSITIVE HCS AND UNDERLYING SUPPORTING CELLS. THE DEVELOPMENT OF THIS INNER EAR ORGANOID MODEL FACILITATES THE PROGRESS OF CELL-BASED ASSAYS FOR STUDYING HC-SPECIFIC DEVELOPMENT AND TESTING POTENTIAL TREATMENTS FOR SENSORY CELL LOSS. IN THIS PROPOSAL, I AIM TO UTILIZE THE INNER EAR ORGANOID MODEL TO INVESTIGATE THE TRANSCRIPTIONAL CONTROL OF HC DEVELOPMENT IN VITRO. TO ACHIEVE THIS, I PLAN TO: I. DEFINE THE TFS INVOLVED IN IN VITRO INNER EAR ORGANOID HC DEVELOPMENT COMPARED TO IN VIVO HC DEVELOPMENT. II. GENERATE A VERSATILE TOOLKIT OF MESC LINES DESIGNED FOR INDUCIBLE AND REVERSIBLE CRISPR-MEDIATED GENE ACTIVATION AND INHIBITION. III. UTILIZE THIS TOOLKIT TO SYSTEMATICALLY INVESTIGATE THE ROLES OF CANDIDATE TFS IN ORGANOID HCS THROUGH CRISPR-MEDIATED KNOCKDOWN AND ACTIVATION, FOLLOWED BY MULTI-OMIC ANALYSES. SUCCESSFUL COMPLETION OF THIS PROJECT WILL NOT ONLY UNCOVER ADDITIONAL TFS ESSENTIAL FOR HC DEVELOPMENT BUT WILL ALSO PROVIDE A VALUABLE RESOURCE FOR FELLOW INNER EAR RESEARCHERS SEEKING TO MANIPULATE THE EXPRESSION OF GENES OF INTEREST WITHIN INNER EAR ORGANOID CELL TYPES.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $0 | 12/23/25 | ||
| Not listed | $21.5k | 7/10/25 | ||
| Not listed | $21.5k | 7/10/25 | ||
| Not listed | $128.9k | 6/12/24 |