This is the first book to collect and summarize in one publication the efforts to use kinases or phosphatases for drug development against parasite infections. The editors and contributors comprise the Who's Who in the field, and they are comprehensive in covering every aspect of the topic, from basic research findings to translational approaches in drug development. The result will be welcomed by everyone in academia and industry participating in the global effort to finally combat the major diseases caused by eukaryotic parasites. This is volume one of a two-volume treatise, the second being exclusively dedicated to efforts to combat malaria using the same approach.
List of Contributors XV
Part One Bioinformatics 1
1 Computational Analysis of Apicomplexan Kinomes 3
Eric Talevich, Natarajan Kannan, and Diego Miranda-Saavedra
2 Phosphatomes of Unicellular Eukaryotic Parasites 37
Alexandra V. Andreeva and Mikhail A. Kutuzov
Part Two Functional Analysis of Parasite Kinomes and Phosphatomes 61
3 Trypanosomatid Phosphoproteomics 63
Michael D. Urbaniak
4 Trypanosomatid Cell Division Kinases 79
Corinna Benz, Elizabeth Thomas, and Tansy C. Hammarton
5 Kinetoplastid AGC Kinases 99
Sabine Bachmaier and Michael Boshart
6 Plasmodium eIF2a Kinases 123
Daniel E. Goldberg, Min Zhang, and Victor Nussenzweig
7 Protein Kinases of the Parasitic Protist Entamoeba histolytica 131
Somlata, Mrigya Babuta, Sudha Bhattacharya, and Alok Bhattachary
8 Protein Phosphatases in Trypanosome Growth and Development 155
Balazs Szoor and Keith R. Matthews
Part Three Role of Host Cell Kinomes and Phosphatomes in Parasitic Infections 179
9 Hijacking of Host Cell Signaling by Theileria 181
Kerry Woods, Conrad von Schubert, and Dirk Dobbelaere
10 The Role of Host- and Parasite-Encoded Kinases in Toxoplasma–Host Interactions 199
Ira J. Blader, Gustavo Arrizabalaga, and William J. Sullivan Jr
11 Macrophage Kinases in Leishmaniasis 217
Mahesh Kumar Padwal, Uddipan Sarma, Raki Sudan, and Bhaskar Saha
Part Four Drug Discovery 235
12 Selective Inhibition of Parasite Protein Kinases 237
Jennifer D. Artz, Amy K. Wernimont, Linda. Y. Lin, Merhnaz Amani, Mirela Neculai, Tanya Hills, and Raymond Hui
13 Kinase Inhibitors Among Hits from Malaria Cellular Screens 261
James R. Brown, David Drewry, Francisco-Javier Gamo, and Jose F. Garcia-Bustos
14 Calcium-Dependent Protein Kinases of Apicomplexan Parasites as Drug Targets 293
Kayode K. Ojo, Ethan A. Merritt, Dustin J. Maly, and Wesley C. Van Voorhis
15 Protein Kinases as Suitable Targets for Combating Eimeria spp. 317
Richard J. Marh€ofer, Jeremy C. Mottram, and Paul M. Selzer
16 Receptor Tyrosine Kinase Signaling and Drug Targeting in Schistosomes 337
Colette Dissous, Mathieu Vanderstraete, Svenja Beckmann, Nadege Gouignard, Silke Leutner, Christin Buro, and Christoph G. Grevelding
17 Protein Kinases as Drug Targets in the Treatment of Alveolar Echinococcosis 357
18 Collaborative Drug Design of Plasmodium Kinase Inhibitors 375
Barry Hardy, Roman Affentranger, Alessandro Contini, Hugo Gutierrez de Teran, Jeff Spitzner, Ruben Papoian, William L. Seibel, Sandra Nelson, Jeffrey Wiseman, Sharon D. Bryant, Isabelle Lucet, and Christian Doerig
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Christian Doerig obtained his PhD in molecular virology at the Swiss Institute for Experimental Cancer Research in Lausanne, Switzerland. After a post-doctoral training on herpes simplex virus in the USA, he turned his attention to malaria and pioneered the study of protein phosphorylation in Plasmodium. He is Directeur de Recherches at the French biomedical research agency Inserm and established the first Inserm units in the UK at the Wellcome Trust Centre for Molecular Parasitology, University of Glasgow and subsequently in Switzerland at the Inserm-EPFL joint laboratory, Ecole Polytechnique Federale de Lausanne. In 2011, he joined Monash University in Melbourne, AUS, as Head of the Department of Microbiology, focusing on kinomics, cell proliferation, and development of malaria parasites.
Gerald Späth studied biology at the Johannes Gutenberg University, Mainz, Germany. He carried out his PhD thesis at the Institut Pasteur and joined Washington University Medical School in Saint Louis, USA, to carry out his post-doctoral training on the analysis of Leishmania virulence genes. He obtained his first faculty appointment in 2001 at the NYU Medical School, New York, USA, and created his research unit in 2005 at the Institut Pasteur in Paris, France, where he applies phospho-proteomics approaches to define Leishmania-specific signaling pathways as novel drug targets. Gerald Spath is currently Associate Professor at the Institut Pasteur, where he coordinates the Leishmania research of the Institut Pasteur International Network.
Martin Wiese studied biology, microbiology, biochemistry and parasitology at the Universities of Karlsruhe and Tubingen, Germany. He obtained his PhD for his studies on Leishmania at the Max-Planck Institute for Biology, laying the foundation for his studies on mitogen-activated protein kinases of Leishmania. In 2001 he became independent research group leader at the Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany. Since 2007 he is a John Anderson Research Senior Lecturer at the University of Strathclyde, Glasgow, UK. His research is focused on parasite protein kinases as drug targets and the identification of signaling pathways in Leishmania using phosphoproteomics, molecular parasitology and protein biochemistry.
Paul M. Selzer studied biology, parasitology, and biochemistry at the University of Tubingen, Germany, where he also received his PhD in biochemistry. He spent three years at the Molecular Design Institute and the Parasitology and Tropical Disease Research Laboratory at the University of California, San Francisco. During his career he has worked as a researcher and scientific manager for several pharmaceutical companies, and is currently Director, Molecular Discovery Sciences at MSD Animal Health Innovation GmbH, Germany. He is also a visiting professor and teacher at the Biochemistry Institute of the University of Tubingen, and an honorary professor of the Department of Infection, Immunity, and Inflammation at the University of Glasgow, UK.