Dr. Shane R. Cunha
The University of Texas Health Science Center at Houston
Department of Integrative Biology and Pharmacology
- Protein targeting
- Membrane excitability
- Excitation/contraction coupling in cardiomyocytes
- Cardiac arrhythmia (long QT syndrome, Brugada syndrome)
Mechanisms of membrane formation and cellular excitability:
Ankyrins are a family of adaptor proteins that tether membrane-associated proteins to the underlying cytoskeleton in a variety of cell types. In excitable cells, ankyrins facilitate the targeting and retention of ion channels and transporters to electrogenic domains such as the nodes of Ranvier in neurons and transverse-tubules in ventricular cardiomyocytes. The association of ankyrin dysfunction with human diseases such as hereditary spherocytosis, cardiac arrhythmias, and epilepsy highlights the clinical relevance of ankyrins for normal human physiology.
Our lab is interested in the molecular mechanisms of ankyrin function in cardiomyocyte structure and membrane excitability using the mammalian heart as our model system. We employ a variety of techniques in molecular and cellular biology, biochemistry, and cell imaging in addition to using mouse models of cardiac arrhythmia and primary cultures of cardiac cells.
Cunha SR, Mohler PJ (2009) Ankyrin protein networks in membrane formation and stabilization. J Cell Mol Med 13(11-12): 4364-76.
Cunha SR, Mohler PJ (2008) Obscurin targets ankyrin-B and protein phosphatase 2A to the cardiac M-line. J Biol Chem 283(46): 31968-80.
Le Scouarnec S, Bhasin N, Vieyres C, Hund TJ, Cunha SR, Koval O, Marionneau C, Chen B, Wu Y, Demolombe S, Song LS, Le Marec H, Probst V, Schott JJ, Anderson ME, and Mohler PJ (2008) Dysfunction in ankyrin-B-dependent ion channel and transporter targeting causes human sinus node disease. Proc Natl Acad Sci, USA 105(40): 15617-22.
Cunha SR, Le Scouarnec S, Schott JJ, Mohler PJ (2008) Exon organization and novel alternative splicing of the human ANK2 gene: implications for cardiac function and human cardiac disease. J Mol Cell Cardiol 45(6): 724-34.
Cunha SR, Bhasin N, and Mohler PJ (2006) Targeting and stability of Na/Ca exchanger 1 in cardiomyocytes requires direct interaction with the membrane adaptor ankyrin-B. J Biol Chem 282(7): 4875-83.