| Grant number: | 18/03433-9 |
| Support type: | Regular Research Grants |
| Duration: | September 01, 2018 - May 31, 2021 |
| Field of knowledge: | Health Sciences - Medicine - Surgery |
| Principal researcher: | Karina Lezirovitz Mandelbaum |
| Grantee: | Karina Lezirovitz Mandelbaum |
| Home Institution: | Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
| Assoc. researchers: | Ana Carla Batissoco |
Abstract
Hearing loss is the most frequent sensory defect in humans, can have social, financial, vocational and educational impact for life. The study of deafness genes has contributed decisively to the knowledge of auditory physiology and to the development of strategies of how to intervene to restore it. However, there is still a substantial fraction of deafness genes to be identified. This research project aims to confirm the identity of the DFNA58 gene and uncover the pathophysiological mechanism underlying this form of post-lingual and progressive hearing loss, present in a Brazilian family and whose locus was mapped in 2009 by the proponent of this grant. The biological pathway, that this novel deafness gene belongs to, was never described as involved in hearing. Thus, this project aims to prove that this gene is indeed essential to the normal physiology of hearing and to elucidate the underlying defect that leads to hearing impairment, recapitulating the effects the altered expression of this gene in a cellular and animal model, through two strategies: 1) to obtain IPS cells (induced pluripotent stem cells) from of the samples of individuals with hearing loss carriers of the duplication and noncarriers (normal hearing or hearing impaired with different clinical presentation) from the family, to differentiate them in neurons and hair cells and to compare them for the metabolic differences. 2) to study the effect of its altered expression on the development of the otic capsule in zebrafish. (AU)