Michael Welsh, M.D.
Insights into the Pathogenesis of Cystic Fibrosis
The Welsh
laboratory puts emphasis in three main areas. The first is understanding the
biology of cystic fibrosis, a common lethal genetic disease. The lab is
studying the function of the CF gene product, the CFTR Cl- channel.
We are investigating how the normal protein forms the Cl- channel
and how its activity is regulated. We hope to understand the structure and
function of the normal channel and how mutations cause dysfunction. We are also
focusing on the pathogenesis of the disease, learning how the loss of CFTR Cl-
channels leads to airway infections.
Second, the laboratory is developing gene transfer as a potential treatment for cystic fibrosis and other diseases. We currently focus on adenovirus and cationic lipid-based vectors. The laboratory is using in vitro and animal model systems to develop better vector systems. As the work proceeds, we will test specific hypotheses in humans.
Third, the laboratory is studying the cellular and molecular biology of a new class of nonvoltage-gated Na+ channels that includes the amiloride-sensitive Na+ channel (ENaC), and the degenerins from C. elegans. The work is focused on understanding how the various subunits come together to form a channel as well as the conductive and regulatory functions of the channels. We are developing model systems in Drosophila and mice to understand better the physiology of the channels. The laboratory is also studying how dysfunction of these channels causes diseases such as hypertension and neurodegeneration.