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Dr Virgilio L Lew and Dr Teresa Tiffert

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Tel: +44 (0)1223 333830, Fax: +44 (0)1223 333840, E-mail: vll1@cam.ac.uk

Research interests
Recent advances in biochemistry, biophysics and molecular biology have provided a wealth of information about the molecular components responsible for complex cellular functions and responses. A major pursuit in our laboratory is the understanding of how these components interact together in intact cells to ensure their osmotic stability in physiological, pathophysiological and experimental conditions. We pioneered the development and application of integrated mathematical models of epithelial cell function, and of cell volume, pH and ion content regulation in red cells, reticulocytes, and more recently, of the homeostasis of malaria-infected red cells. These homeostatic models delivered many novel and unexpected predictions, largely confirmed experimentally, which have helped solve outstanding issues on epithelial and erythroid cell function, and on the pathophysiology of sickle cell anaemia. Recent interests include the processes of pre-invasion and egress of falciparum merozoites in human red blood cells, mechanisms of spontaneous membrane vesiculation and fusion, and modelling of guard cell homeostasis and stomatal dynamics (in collaboration with colleagues from theLaboratory of Plant Physiology and Biophysics, University of Glasgow).

Selected recent publications
Lew, V.L., Tiffert, T. and Ginsburg, H. (2003). Excess hemoglobin digestion and the osmotic stability of Plasmodium falciparum-infected red blood cells. Blood, 101, 4189-4194

Lew, V. L., Daw, N., Perdomo, D., Etzion, Z, Bookchin, R. M. and Tiffert, T. (2003). Distribution of plasma membrane Ca2+ pump activity in normal human red blood cells. Blood, 102, 4206-4213.

Lew, V.L. (2004). A choline "vacuum cleaner". Blood, 104, 3006-3007

Lew, V.L. and Bookchin, R.B. (2005). Ion transport pathology in the mechanism of sickle cell dehydration. Physiol. Rev. 85, 179-200

Tiffert, T., Lew, V.L., Ginsburg, H., Krugliak, M., Croisille, L., and Mohandas, N. (2005). The hydration state of human red blood cells and their susceptibility to invasion by Plasmodium falciparum. Blood, 105, 4853-4860.

Tiffert, T., Daw, N., Etzion, Z., Bookchin, R.M., and Lew, V.L. (2007). Age decline in the activity of the Ca2+ -sensitive K+ channel of human red blood cells. J. Gen. Physiol., 129, 429-436.

Lew, V.L., Daw, N., Etzion, Z., Tiffert, T., Muoma, A., Vanagas, L., Bookchin, R.M. (2007). Effects of age-dependent membrane transport changes on the homeostasis of senescent human red blood cells. Blood, 110, 1334-1342.

Lew, V.L., and Tiffert, T. (2007). Is invasion efficiency in malaria controlled by pre-invasion events? Trends in Parasitology, 23, 491-494.

Esposito, A., Tiffert, T., Mauritz, J.M., Schlachter, S., Bannister, L.H., Kaminski, C.F. and Lew, V.L. (2008). FRET imaging of Hemoglobin Concentration in Plasmodium falciparum-infected red cells. PLoS One, 3, e3780

Bookchin, R.M., Etzion, Z., Lew, V.L., and Tiffert, T. (2009). Preserved function of the plasma membrane calcium pump of red blood cells from diabetic subjects with high levels of glycated haemoglobin. Cell Calcium, 45, 260–263

Mauritz, J.M.A., Esposito, A., Ginsburg, H., Kaminski, C.F., Tiffert, T. and Lew, V.L. (2009). The homeostasis of Plasmodium falciparum-infected red blood cells. PLoS Computational Biology, 5, e1000339

Alessandro Esposito, Jean-Baptiste Choimet, Jeremy N. Skepper, Jakob M. A. Mauritz, Virgilio L. Lew, Clemens F. Kaminski, and Teresa Tiffert. 2010. Quantitative imaging of human red blood cells infected with Plasmodium falciparum. Biophys. Journal, 99, 1-8

Doron Kabaso, Roie Shlomovitz, Thorsten Auth, Virgilio L. Lew and Nir S. Gov. 2010. Curling and local shape changes of red blood cell membranes driven by cytoskeletal reorganization. Biophys. Journal, 99, 808-816

Swietach, P., T. Tiffert, J.M.A. Mauritz, R. Seear, A. Esposito, C.F. Kaminski, V.L. Lew and R.D. Vaughan-Jones. 2010. Hydrogen ion dynamics in human red blood cells. J. Physiol., 588, 4995–5014

Mauritz, J.M.A., R. Seear, A. Esposito, C.F. Kaminski, J.N. Skepper, A. Warley, V.L. Lew and T. Tiffert. 2011. X-ray microanalysis investigation of the stage-related changes in Na, K and hemoglobin concentration in Plasmodium falciparum-infected red blood cells. Biophys. J., 100, 1438-1445

Lew, V.L. 2011. Malaria: surprising mechanism of merozoite egress revealed. Current Biology, 21, R314-R316.