Ashley Fisher

Current Position:

Senior Scientist, Preclinical Development at SIGA Technologies, Inc., Corvailis, OR

Education:

• Ph.D. Pharm/Tox University of Arizona, Tucson, AZ 2004-2009
• B.A. Chemistry The College of Wooster, Wooster, OH 2001

Achievements:

• NIEHS Toxicology and Toxicogenomics Training Program Predoctoral Trainee 2007-2008
• 2nd place poster presentation, regional MWSOT 2005
• Honorable mention best student presentation at annual SOT Carl C. Smith Graduate Student Award for Meritorious Research in Mechanisms of Toxicology 2006 and 2008 
• 2^nd and 3^rd Place in the Graduate Student Best Paper Competition sponsored by the Divison of Toxicology, American Society of Pharmacology and Experimental Therapeutics, FASEB, respectively 2006 and 2007

Professional Experience:

• Research Assistant, University of Arizona, Tucson, AZ 2003-2009
• Research Assistant, Northwestern Medical School, Chicago, IL 2002-2003
• Laboratory Assistant, Unilever Inc., Rolling Meadows, IL 2001-2002

Research Project:

Hydroquinone (HQ) is a toxicant that is the product of benzene metabolism, and HQ metabolism leads to several more toxic compounds including benzoquinone (BQ) and the glutathione conjugates of HQ (HQGSH). Mass spectrometry techniques are utilized to identify the adducted proteins as well as determine the specific adduction site. Following the identification of these proteins, the structural and functional consequences of the adductions need to be assessed.

Because only macromolecules with accessible nucleophilic groups will become adducted, a common binding motif may exist within the adducted proteins. In efforts concentrated on determining the existence of this “electrophile binding motif”, we propose to utilize molecular modeling as a way of viewing the residues within the proteins. The program used to facilitate this modeling approach is called Insight II. This program is designed to display, build, manipulate, simulate, and analyze molecular structures, as well as calculate the properties of these structures. The ability to visualize the molecules allows for immediate assessment of a particular structure, such as viewing the solvent-exposed residues as well as highlighting particular amino acids. A protein structure that has been assessed in this manner is cytochrome c with adductions including BQ and HQGSH. The biological consequences of these protein adductions will also be assessed using activity assays.

Publications:

• Fisher, A.A., Labenski, M.T., Malladi, S., Chapman, J.D., Bratton, S.B., Monks, T.J. and Lau, S.S. The frequency of 1,4-benzoquinone-lysine adducts in cytochrome c correlate with defects in apoptosome activation. Toxicol. Sci. 122(1): 64-72, 2011.
• Fisher, A.A., Labenski, M.T., Monks, T.J., and Lau, S.S. Mass spectrometry-based methods to identify chemical modifications on proteins. I. Utilization of MALDI-TOF to determine chemical-protein adduct formation in vitro. In: Gautier, J.-C. (ed.). Drug Safety Evaluation Series - Methods of Molecular Medicine. Humana Press 2010; 303-16.
• Fisher, A.A., Labenski, M.T., Monks, T.J, and Lau, S.S. Mass spectrometry-based methods to identify chemical modifications on proteins: II. Utilization of LC-MS/MS analyses to identify site-specific chemical protein adducts in vitro. In: Gautier, J.-C. (ed.). Drug Safety Evaluation Series - Methods in Molecular Medicine. Humana Press 2010; 317-26.
• Labenski, M.T., Fisher, A.A., Monks, T.J., and Lau, S.S. Mass spectrometry-based methods to identify chemical modifications on proteins. III. One dimensional western blotting coupled to LC-MS/MS analysis to identify chemical-adducted proteins in urine. In: Gautier, J.-C. (ed.). Drug Safety Evaluation Series - Methods of Molecular Medicine. Humana Press 2010; 327-38.
• Labenski, M.T., Fisher, A.A., Monks, T.J., and Lau, S.S. Mass spectrometry-based methods to identify chemical modifications on proteins. IV. Identification of chemical-adducted proteins in urine by multi-dimensional protein identification technology (LC/LC-MS/MS). In: Gautier, J.-C. (ed.). Drug Safety Evaluation Series - Methods of Molecular Medicine. Humana Press 2010; 339-50.
• Fisher, A.A., Labenski, M.T., Gokhale, V., Bowen, M.E., Milleron, R.S., Bratton, S.B., Monks, T. J. and Lau, S.S. Quinone electrophiles selectively adduct “electrophile binding motifs” within cytochrome c. Biochemistry, 46:11090-11100, 2007.