Rapid movements of molecules across biological membranes are critical for many fundamental processes such as muscle contraction, neural conduction, and epithelial ion transport. An understanding of the molecular biology of many of the transport proteins involved in these processes is beginning to emerge. It is also becoming clear that mutations in genes encoding proteins that alter membrane transport are associated with inherited disorders such as cystic fibrosis and polycystic kidney disease. We use a combination of cell and molecular approaches to study the structure, function, regulation, development, and molecular biology of ion channels and the role of transport proteins in the disease process. Areas of current interest include:
- Expression and structure/function studies of CI-and water channels;
- Identification of the specific defect in CI- channel regulation in patients with Cystic Fibrosis, the most common autosomal recessive disease in North America;
- Genetic therapies for the correction of defective ion transport in CF cells and patients.
- Understanding the molecular defect in polycystic kidney disease a common autosomal dominant disorder.
- Devuyst O, Guggino WB. Chloride channels in the kidney: lessons learned from knockout animals. Am J Physiol Renal Physiol 2002 Dec;283(6):F1176-91.
- Wang SX, Ikeda M, Guggino WB. The cytoplasmic tail of large conductance, voltage- and Ca2+-activated K+ (MaxiK) channel is necessary for its cell surface expression. J Biol Chem 2002 Nov 15; [epub ahead of print].
- Beck SE, Laube BL, Barberena CI, Fischer AC, Adams RJ, Chesnut K, Flotte TR, Guggino WB. Deposition and expression of aerosolized rAAV vectors in the lungs of Rhesus macaques. Mol Ther 2002 Oct;6(4):546-54.
- Ikeda M, Beitz E, Kozono D, Guggino WB, Agre P, Yasui M. Characterization of aquaporin-6 as a nitrate channel in mammalian cells. Requirement of pore-lining residue threonine 63. J Biol Chem 2002 Oct 18;277(42):39873-9.
- Guggino WB. Cystic fibrosis salt/fluid controversy: in the thick of it. Nat Med. 2001 Aug;7(8):888-9.
- Hanaoka K, Qian F, Boletta A, Bhunia AK, Piontek K, Tsiokas L, Sukhatme VP, Guggino WB, Germino GG. Co-assembly of polycystin-1 and -2 produces unique cation-permeable currents. Nature. 2000 Dec 21-28;408(6815):990-4.
- Wang S, Yue H, Derin RB, Guggino WB, Li M. Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity. Cell. 2000 Sep 29;103(1):169-79.