We study different aspects of the biology of voltage-gated potassium channels, from the molecular mechanisms of channel gating to their potential use in cancer therapy. Our approaches include biochemical, biophysical, cell biological techniques and animal models. Most relevant to IonTraC, we design engineered proteins to delete tumor cells based on the specific expression of ion channels on their surface.
Figure: KV10.1 potassium channels are implicated in a variety of cellular processes including cell proliferation and tumour progression. Their expression in over 70% of human tumours makes them an attractive diagnostic and therapeutic target. Although their physiological role in the central nervous system is not yet fully understood, advances in their precise cell localization will contribute to the understanding of their interactions and function.
The KV10.1 channel has two different populations in a 3:2 ratio, one associated to and another excluded from Detergent Resistant Membranes (DRMs). This distribution of KV10.1 in isolated PM is cholesterol- and cytoskeleton-dependent since alteration of those factors changes the relationship to 1:4. (http://www.sciencedirect.com/science/article/pii/S0005273613004045)
F. Hartung, W. Stühmer, L. A. Pardo Tumor cell-selective apoptosis induction through targeting of KV10.1 via bifunctional TRAIL antibody. Mol Cancer 10, 109 (2011).
S. Herrmann, M. Ninkovic, T. Kohl, E. Lörinczi, L. A. Pardo, Cortactin controls surface expression of the voltage-gated potassium channel KV10.1. J Biol Chem 287, 44151-44163 (2012).
A. Barrantes-Freer, E. Kim, J. Bielanska, A. Giese, L. S. Mortensen, W. J. Schulz-Schaeffer, C. Stadelmann, W. Bruck, L. A. Pardo, Human glioma-initiating cells show a distinct immature phenotype resembling but not identical to NG2 glia. J Neuropathol Exp Neurol 72, 307-324 (2013).
A. M. Jimenez-Garduno, M. Mitkovski, I. K. Alexopoulos, A. Sanchez, W. Stuhmer, L. A. Pardo, A. Ortega, KV10.1 K(+)-channel plasma membrane discrete domain partitioning and its functional correlation in neurons. Biochim Biophys Acta 1838, 921-931 (2014).
L. A. Pardo, W. Stühmer, The roles of K+ channels in cancer. Nat Rev Cancer 14, 39-48 (2014).
D. Urrego, A. P. Tomczak, F. Zahed, W. Stuhmer, L. A. Pardo, Potassium channels in cell cycle and cell proliferation. Philos Trans R Soc Lond B Biol Sci 369, 20130094 (2014).