Deafness and blindness are the most prevalent sensory impairments in humans, affecting all age groups, from children/young (1/500 and 1/4000, respectively) to elders (over 50% and 10% of the 75+ years old, respectively). These major sensory deficits still represent unmet medical needs, since treatment options are largely missing and the economic burden on healthcare systems worldwide keeps increasing. The research in the team is designed, keeping strong roots on important basic science questions, such as maintenance overtime of auditory hair cells’ proper activity, molecular underpinnings of signal transduction of sensory stimuli and their transmission to the brain, the impact of environment and/or aging on the disease progression, and design of neuroprotection strategies.
Today, about 100 deafness genes (several of which are involved in Usher syndrome (USH), the major cause of deafness and blindness in humans have been identified (see http://hereditaryhearingloss.org/), and many more are yet to be identified. Over the last two decades, tremendous progress has been made with the discovery of genes involved in congenital, or early onset profound hearing loss, and elucidation of the underlying mechanisms, grouping the causative genes in specific functional subcategories: i) development and functioning of the hair bundle (sound receptive structure), ii) synaptic transmission, iii) cell-cell adhesion, iv) ion homeostasis, v) extracellular matrix, vi) oxidative stress and mitochondrial defects, vii) transcriptional regulation, etc…. By contrast, a similar in-depth understanding of the deafness-involved mechanisms is still lacking for progressive/late inherited or acquired hearing loss, as are the molecular underpinnings of activity maintenance and survival of hair cells and associated neurons.
The team’s projects are centered on progressive and/or late sensory disorders, with two main objectives: (1) fundamental: gain better understanding of genetic, molecular and cellular mechanisms in normal and disease conditions, with keen attention to potential impact of aging and environment on disease progression, and (2) medical: based on uncovered pathogenic process, devise, test and evaluate in preclinical animal models, potential therapies to prevent, halt, and/or delay sensory deficits.
