The Welsh laboratory emphasizes three main areas. The first is understanding the biology of cystic fibrosis (CF), a common lethal genetic disease. Cystic fibrosis is caused by mutations in a gene that encodes the CFTR chloride channel. Welsh and his colleagues are learning how the CFTR chloride channel is regulated, how it forms a chloride pore in the cell membrane, and how mutations disrupt its function. They also focus on the pathogenesis of cystic fibrosis lung disease, learning how the loss of CFTR causes bacterial airway infections and how bacteria interact with the airway. They are using this knowledge to develop novel treatments. This work also involves clinical research to study pathogenesis and interventions in people with CF.
Second, Welsh and his colleagues are developing gene therapy to treat cystic fibrosis and other genetic diseases. They are studying adenovirus, adeno-associated virus, and non-viral vectors. The studies include basic vectorology, pre-clinical studies, and studies in humans.
Third, the lab studies the cellular and molecular biology and physiology of the novel DEG/ENaC cation channel family. In the peripheral nervous system, these channels contribute to the detection of the touch, pain, temperature, and salty taste. In the central nervous system, they are involved in memory and the fear response. This work should lead to a better understanding of neuronal sensory systems and novel targets for therapeutic interventions.