Research Assistant Professor
Phone: (612) 624-5172
B.S. Chemistry, St. Cloud State University
M.S. Biological Chemistry, University of Michigan
Ph.D. Biological Chemistry, University of Michigan
HIV lethal mutagenesis; HIV quasispecies
The high mutation rate of HIV allows for the development of drug resistance and the ability of the virus to escape immune detection. However, many mutations produced during the error-prone replication are detrimental to the virus and lead to the production of non-infectious virus. The error rate of HIV-1 is high enough to ensure enough diversity for the virus to replicate under adverse conditions such as the presence of antiviral compounds or immune surveillance, yet low enough that the virus does not accumulate enough mutations to render the virus non-infectious. It has been predicted that increasing the mutation rate above a certain threshold, known as the error threshold, would extinguish viral infectivity. As a result, drugs that increase the mutation frequency of HIV-1 past the error threshold may be a viable antiretroviral therapy. To test this, I am investigating the effects of two FDA-approved drugs (decitabine and gemcitabine) on their ability to eliminate HIV infectivity by elevating the HIV mutation rate. These studies represent a collaboration with Louis Mansky and Steven Patterson. Presently, I am extending my studies into mouse model and working on methods to deliver these drugs in a pill form. I am interested in the clinical translation of this novel combination therapy.
My graduate work at the University of Michigan focused on post-translational processing and trafficking of the Luteinizing Hormone Receptor, a GPCR critical for reproduction. While in Michigan, both course and volunteer work sparked my interest in virology with a specific focus on HIV.
In my free time, I enjoy outdoor activities and am an avid reader.
Selected Recent Publications
Greggs, W.M., Clouser, C.L., Patterson, S.E., and L.M. Mansky. 2011. Broadening the use of antiretroviral therapy: the case for feline leukemia virus. Therapeutics and Clinical Risk Management Epub ahead of print
Clouser, C.L., Holtz, C.M., Mullet, M., Crankshaw, D.L., Briggs, J.E., Chauhan, J., VanHoutan, I.M., Patterson, S.E., and L.M. Mansky. 2010. Analysis of the ex vivo and in vivo antiretroviral activity of gemcitabine. PLoS One 6:e15840.
Ni, Z., Knorr, D.A., Clouser, C.L., Hexum, M.K., Southern, P., Mansky, L.M., Park, I.-H., and D.S. Kaufman. 2010. Human pluripotent stem cells produce natural killer cells that mediate anti-HIV-1 activity utilizing diverse cellular mechanisms. Journal of Virology 84: Epub ahead of print
Clouser, C.L., Patterson, S.E., and L.M. Mansky. 2010. Exploiting drug repositioning for the discovery of a novel HIV combination therapy. Journal of Virology 84:9301-9309.
Dapp, M.D., Clouser, C.L., Patterson, S.E. and L.M. Mansky. 2009. 5-Azacytidine can induce lethal mutagenesis in human immunodeficiency virus type 1. Journal of Virology 83:11950-58.
My Research in the News
KARE 11 TV
U of M Academic Health Center