PhD Krister Wennerberg and PhD Denis Kainov selected FIMM-EMBL Group Leaders

Krister Wennerberg received his undergraduate degree from Uppsala University in Sweden and went on to his graduate studies at the same university, in Staffan Johansson's group where he studied b1 integrins and the cytoplasmic domain of the b1 subunit.

After obtaining his Ph.D. he began his postdoc joint between the laboratories of Keith Burridge and Channing Der at the University of North Carolina in 2000. As a postdoc, he worked on the regulation of small G-proteins and developed activity-based functional proteomics approaches to study these events. In 2004, he took a research and development scientist position at Cytoskeleton, Inc a small biotech company in Denver, CO, USA followed in 2006 by a group leader position at the Drug Discovery Division of Southern Research Institute, a research institute in Birmingham, AL, USA.

At Southern Research, Krister has been managing an internal drug discovery program and leading an assay development group and has in the process been involved in most aspects of early drug discovery, from target identification and -validation to assay development, high throughput screening, hit-to-lead and lead optimization. His own research at Southern Research has been focused on 1) targeting novel mitotic and cytokinetic proteins such as small G-protein regulators and kinesins by the development of specific small molecule inhibitors and 2) using activity-based profiling technologies for putative druggable classes of targets such as adenine and guanine nucleotide-binding and - hydrolyzing proteins to probe biology and identify novel molecular drug targets.

At FIMM, the Wennerberg lab will continue the two chemical biology research paths started at Southern Research; exploring mitotic biology and cancer through the development and use of novel small molecule mitotic inhibitors and using activity-based profiling to discover novel putative drug targets in cancer and other diseases. In both research paths, the long-term goals are to gain fundamental understanding of the biological systems studied as well as initiating full drug discovery efforts against some of the molecular targets.

Selected publications:

Swenson-Fields KI, Sandquist JC, Rossol-Allison J, Blat IC, Wennerberg K, Burridge K, Means AR. 2008. MLK3 limits activated Galphaq signaling to Rho by binding to p63RhoGEF. Mol. Cell. 32:43-56.

Dubash AD, Wennerberg K, García-Mata R, Menold MM, Arthur WT, Burridge K. 2007. A novel role for Lsc/p115 RhoGEF and LARG in regulating RhoA activity downstream of adhesion to fibronectin. J. Cell Sci. 120:3989-3998.

Wennerberg K, Forget MA, Ellerbroek SM, Arthur WT, Burridge K, Settleman J, Der CJ, Hansen SH. 2003. Rnd proteins function as RhoA antagonists by activating p190 RhoGAP. Curr. Biol. 2003 13:1106-1115.

Arthur WT, Ellerbroek SM, Der CJ, Burridge K, Wennerberg K. 2002. XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC. J. Biol. Chem. 277:42964-42972.

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The scientific career of Denis Kainov started in 2001 in the Institute of Protein Research, Moscow, Russia, where he studied regulation of gene expression under supervision of Prof. Nick Matvienko. In 2001 he joined Professor Dennis Bamford team at the Institute of Biotechnology, University of Helsinki, Finland, where he studied how RNA viruses from the Cystoviridae family assemble nucleocapsid particles from protein constituents and RNA genomic segments.

Denis Kainov obtained his PhD in 2005. In the same year (2005) he received EMBO long-term postdoctoral fellowship and joined the laboratory of Prof. Jean-Marc Egly in the IGBMC, Strasbourg, France. His research was focused on small protein, mutations in which cause group A Trichotyodystrophy. Denis Kainov characterized this protein and its partners using biochemical and structural biology approaches providing valuable insights into molecular mechanisms of this disease.

In 2007 Denis Kainov started a second postdoctoral project in the Institute of Immunology in Luxembourg. He developed a new strategy to treat influenza infection. Denis Kainov will continue developing strategies to treat viral infection by joining the Medical Systems Biology research area of FIMM. He will establish a new research group on Medical Systems Virology with immediate translational opportunities.

The goals of the group are: 1) to provide a comprehensive molecular portrait of virus-host cell interactions using virus reverse genetics, proteomics, high-throughput siRNA and compound screening techniques; 2) to identify determinants of viral transmissibility using viral and human genomics.

Selected publications:

Kainov DE, Vitorino M, Cavarelli J, Poterszman A, Egly JM. (2008) Structural basis for group A trichothiodystrophy. Nat. Struct. Mol. Biol. 15: 980 - 984

Kainov DE, Mancini E, Lisal J, Grimes JM, Bamford D, Stuart DI, and Tuma R. (2008) Structural Basis of Mechano-Chemical Coupling in a Hexameric Molecular Motor. J. Biol. Chem. 283: 3607-3617

Lisal J, Lam TT, Kainov DE, Emmett MR, Marshall AG, Tuma R. (2005) Functional visualization of viral molecular motor by hydrogen-deuterium exchange reveals transient states. Nat. Struct. Mol. Biol. 12: 460-466.

Mancini EJ, Kainov DE, Grimes JM, Tuma R, Bamford DH, Stuart D.I. (2004) Atomic snapshots of an RNA packaging motor reveal conformational changes linking ATP hydrolysis to RNA translocation. Cell. 118: 743-755