Education & Training
- Postdoctoral Fellow
- University of Iowa, 2010
- Postdoctoral Fellow
- Vanderbilt University, 2006
- Northwestern University, 2002
Areas of Interests
- Research Interest
- Mechanisms of membrane formation and cellular excitability
Mechanisms of membrane formation and cellular excitability
Specialized membrane domains are distinct regions within the plasma membrane that have unique functions. These functions may include regulating the movement of select ions across the plasma membrane or facilitating membrane adherence to neighboring structures. The function of a membrane domain is determined by its protein and lipid content. Many cellular processes influence the protein content of a membrane domain including intracellular transport, protein targeting and retention, endocytosis and recycling, and protein stability/degradation. Cytosolic adaptor proteins facilitate the progression of membrane-associated proteins through these cellular processes.
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.
- Wu HC, Yamankurt G, Luo J, Subramaniam J, Hashmi SS, Hu H, Cunha SR. (2015). Identification and characterization of two ankyrin-B isoforms in mammalian heart. Cardiovasc Res., Sep 1;107(4):466-77. doi: 10.1093/cvr/cvv184. PMID:26109584.
- Yamankurt G, Wu HC, McCarthy M, Cunha SR. (2015). Exon organization and novel alternative splicing of Ank3 in mouse heart. PLoS One., May 29;10(5):e0128177. doi: 10, 1371/journal.pone.0128177. eCollection 2015. PMID: 26024478.
- Yamankurt G, Nguyen FT, Mohler PJ, Cunha SR. (2012). Ankyrin-based trafficking and scaffolding of membrane proteins: Implications for plasma membrane stability, formation, and specialization. J Proteomics Bioinform., S4:002.
- Hund TJ, Cunha SR, Mohler PJ. (2011). Principles of Cellular Architecture and Physiology with applications in electrophysiology. Electrophysiological Disorders of the Heart (eds. S Saksena and AJ Camm), Elsevier, Inc.
- Cunha SR, Hund TJ, Hashemi S, Voigt N, Li N, Wright P, Koval O, Li J, Gudmundsson H, Gumina RJ, Karck M, Schott JJ, Probst V, Le Marec H, Anderson ME, Dobrev D, Wehrens XH, Mohler PJ. (2011). Defects in ankyrin-based membrane protein targeting pathways underlie atrial fibrillation. Circ., Epub (Aug 22)
- Cunha SR, Mohler PJ. (2011). Ankyrin-based cellular pathways for cardiac ion channel and transporter targeting and regulation. Semin Cell Dev Biol., 22(2): 166-70.
- Gao Z, Chen B, Joiner ML, Wu Y, Guan X, Koval OM, Chaudhary AK, Cunha SR, Mohler PJ, Martins JB, Song LS, Anderson ME. (2010). I(f) and SR Ca(2+) release both contribute to pacemaker activity in canine sinoatrial node cells. J Mol Cell Cardiol., 49, 33-40.
- Gudmundsson H, Hund TJ, Wright PJ, Kline CF, Snyder JS, Qian L, Koval OM, Cunha SR, George M, Rainey MA, Kashef FE, Dun W, Boyden PA, Anderson ME, Band H, Mohler PJ. (2010). EH domain proteins regulate cardiac membrane protein targeting. Circ Res., 107(1): 84-95.
- Cunha SR, Mohler PJ. (2009). Ankyrin protein networks in membrane formation and stabilization. J Cell Mol Med., 13(11-12): 4364-76.
- Kline CF, Kurata HT, Hund TJ, Cunha SR, Koval OM, Wright PJ, Christensen M, Anderson ME, Nichols CG, Mohler PJ. (2009). Dual role of K ATP channel C-terminal motif in membrane targeting and metabolic regulation. Proc Natl Acad Sci USA, 106(39): 16669-74.
- Cunha SR, Mohler PJ. (2008). Cardiac Cytoskeleton and Arrhythmia: An Unexpected Role for Protein 4.1R in Cardiac Excitability. Circ Res., 103(8): 779-81.
- Sedlacek K, Stark K, Cunha SR, Pfeufer A, Weber S, Berger I, Wichmann HE, Mohler PJ, Hengstenberg C, Jeron A. (2008). Common genetic variants in ANK2 influence QT interval- results from the KORA study. Circ Cardiovasc Genet., 1: 93-99.
- 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.
- Kline CF, Cunha SR, Lowe JS, Hund TJ, Mohler PJ. (2008). Revisiting ankyrin-InsP(3) receptor interactions: Ankyrin-B associates with the cytoplasmic N-terminus of the InsP(3) receptor. J Cell Biochem., 104(4): 1244-53.
- 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.
- Cunha SR and Mohler PJ. (2006). Cardiac ankyrins: essential components for development and maintenance of excitable membrane domains in heart. Cardiovasc Res., 71: 22-29.