Inhibition of mutant connexin channels in KID Syndrome (2022)
Thomas W. White
Professor
Department of Physiology & Biophysics
School of Medicine, StonyBrook University
FIRST is pleased to congratulate Thomas W. White PhD, Professor of Physiology & Biophysics at Stony Brook University School of Medicine for being selected as the 2022 FIRST Research Grant Recipient.
UPDATE March 2023: Results from this work have been published. Read the article here.
Objective:
Mutations in connexin26 (Cx26) that cause keratitis-ichthyosis-deafness (KID) syndrome have increased hemichannel activity. We will test inhibition of mutant hemichannels as a strategy to alleviate the skin pathology of KID syndrome in a mouse model.
Aim:
To test inhibition of mutant connexin hemichannels as a new therapeutic approach in a mouse model that expresses the human Cx26-G45E KID syndrome mutation. These mice have increased hemichannel activity in keratinocytes. We hypothesize that inhibiting the acquired hemichannel activity will improve skin disease.
Personal Statement:
“I have studied connexin biology for 33 years employing a wide variety of electrophysiological, molecular biological, histological and genetic methodologies. I have had NIH grants from the National Eye Institute, National Institute of Arthritis and Musculoskeletal and Skin Disease, and the National Institute of Deafness and Other Communication Disorders, to study how connexins contribute to genetic diseases and normal development of the eye, skin, and ear. In our studies of mutations in connexin26 (Cx26 or GJB2) underlying syndromic and nonsyndromic forms of deafness, we have shown that total loss of Cx26 function is a common outcome in nonsydromic deafness. In addition, we showed that gain of function hemichannel activity was a common feature of keratitis-ichthyosis-deafness (KID) syndrome, and generated a mouse model that fully replicated the epidermal phenotype of KID syndrome patients. In this application, we will test inhibition of hemichannel activity in our mouse model as a novel therapeutic strategy to treat KID syndrome.”
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