Professor David Sheppard
David investigates the root cause of the genetic disorder cystic fibrosis and new therapies for the disease
Professor of PhysiologySchool of Physiology, Pharmacology & Neuroscience
The cystic fibrosis transmembrane conductance regulator (CFTR) is a novel member of the ATP-binding cassette (ABC) transporter superfamily that forms an anion channel with complex regulation. CFTR is predominantly located in epithelia lining ducts and tubes throughout the body, although it is also expressed in some non-epithelial tissues, most notably cardiac myocytes. In epithelia, CFTR provides a pathway for the movement of chloride (Cl-) and bicarbonate anions across the apical (lumen-facing) membrane and a key point at which to regulate the rate of transepithelial salt and water transport.
Dysfunction of the CFTR Cl- channel is associated with a wide spectrum of disease. Mutations that, in general, abolish the function of CFTR cause the genetic disease cystic fibrosis (CF), which affects multiple organ systems in the body. By contrast, some forms of male infertility, chronic pancreatitis and bronchiectasis are caused by mutations that probably preserve partial CFTR function. These conditions, termed CFTR-related diseases, affect a single organ system in the body. Increased or inappropriate activity of the CFTR Cl- channel is associated with other diseases, such as secretory diarrhoea and autosomal dominant polycystic kidney disease.
In our studies of the CFTR, we have three specific research goals:
To understand the relationship between the structure and function of the CFTR Cl- channel
To learn how CF-associated mutations cause a loss of CFTR function
To identify new modulators of CFTR that might prove to be of value in the treatment of disease and elucidate their mechanism of action.
01/11/2018 to 31/12/2022
31/10/2008 to 31/10/2011
THE USE OF HUMAN-MURINE CFTR CHIMERAS TO INVESTIGATE THE COUPLING OF PERMEATION AND GATING IN THE CFTR CHLORIDE CHANNEL
01/05/2005 to 01/05/2008
Mutation-Specific Therapies in Cystic Fibrosis: Current Status and Prospects, Second Edition
- Chapter in a book
- Accepted/In press
Nature Chemical Biology
Journal of Cystic Fibrosis
- E-pub ahead of print
Carbon monoxide-releasing molecules inhibit the cystic fibrosis transmembrane conductance regulator Cl- channel
AJP - Lung Cellular and Molecular Physiology