Dept. of Microbiology and
The principal goal of my research program is to elucidate the molecular mechanisms by which negative-sense RNA viruses infect cells and express their genetic information. Towards this goal, we have four integrated areas of research emphasis, which are:
1) To determine the mechanisms by which the RNA synthesis machinery functions;
To pursue these objectives my group takes a multidisciplinary approach employing molecular genetics, biochemistry, cell biology, high-resolution microscopy, structural biology, tissue culture and mouse infection models. The primary focus of investigation is a prototype of the nonsegmented negative-strand RNA viruses, vesicular stomatitis virus (VSV), reflecting the advanced state of our knowledge of the biology of this virus. To complement our VSV studies, we have extended our research into pathogenic human viruses including Rabies, Ebola, Marburg and Machupo virus.
Cureton DK, Massol RH, Saffrian S, Kirchhausen TL, Whelan SPJ. Vesicular stomatitis virus enters cells through vesicles incompletely coated with clathrin that depend upon actin for internalization. PLoS Pathog. 2009. 5:e1000394.
Heinrich B, Cureton DK, Rahmeh A, Whelan SP. Protein expression redirects vesicular stomatitis virus RNA synthesis to cytoplasmic inclusions. PLoS Pathog. 2010 6(6):e1000958.
Rahmeh AA, Schenk AD, Danek EI, Kranzusch PJ, Liang B, Walz T and Whelan SPJ. Molecular architecture of the vesicular stomatitis virus RNA polymerase. Proc. Natl. Acad. Sci. (USA) 2010. 107(46):20075-80. Epub 2010 Nov 1.
Kranzusch PJ, Schenk AD, Rahmeh AA, Radoshitzky SR, Bavari S, Walz T, and Whelan SPJ. Assembly of a functional Machupo virus polymerase complex. Proc. Natl. Acad. Sci. (USA) 2010. 107(46):20069-74. Epub 2010 Oct 26.
Carette JE*, Raaben M*, Wong AC*, Herbert AS, Obernosterer G, Mulherkar NG, Kuehne AI, Griffin AM, Ruthel G, Dal Cin P, Dye JM§, Whelan SP§, Chandran K§ and Brummelkamp T§ Ebola virus entry requires the cholesterol transporter NPC1. Nature 2011 Aug 24. doi: 10.1038/nature10348 (§ denotes co-corresponding author)
Kranzusch PJ, Whelan SPJ. Arenavirus Z protein controls viral RNA synthesis by locking a polymerase-promoter complex. Proc Natl Acad Sci USA 2011 Nov 21 (Epub ahead of print).