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Lau Laboratory
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Matt Labenski
Current Position:
Research Scientist I, Analytical Pharmacology Group, Avila Therapeutics, Waltham, MA
Education:
- Ph.D. Pharm/Tox University of Arizona, Tucson, AZ 2003-2008
- B.S. Toxicology Northeastern University, Boston, MA 2001
Achievements:
- 1st Place in the Graduate Student Best Paper Competition sponsored by the Divison of Toxicology, American Society of Pharmacology and Experimental Therapeutics, FASEB 2007
Professional Experience:
- Research Assistant, University of Arizona, Tucson, AZ 2003-2008
- Research Associate, PRAECIS Pharmaceuticals Inc., Waltham, MA 2001-2003
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Research
Project:
Hydroquinone is a nephrocarcinogen in male Fischer rats
and a potential human carcinogen. It is a metabolite of benzene, used
by the chemical industry as an oxidizer, and is found in cigarette smoke.
Metabolites of hydroquinone include multiple glutathione additions of
up to 4 with 3 being the most toxic to the kidney and are selective for
the proximal tubular epithelium. Hydroquinone and its metabolites are
all capable of redox cycling and adducting macromolecules within the
cell. My project used proteomics to try and determine what proteins Hydroquinone
and its metabolites are adducting in cells and in vivo. By using mass
spectrometric techniques it is possible to not only identify proteins
being adducted, but to also map the adduction site to the specific amino
acid. Once these proteins are identified it will be important to determine
the structural and functional consequences of these adductions. We utilized both a protein model to determine the structural consequence
and activity assays to see if the protein is still functional.
Another aspect of my project was to examine gene dysregulation in the kidney
using microarray analysis after chronic treatment of rats with 2,3,5-tris-(glutathion-S-yl)hydroquinone
(TGHQ), the most nephrotoxic metabolite of Hydroquinone. This project is meant
to further explore the TGHQ mediated gene changes taking place that result
in renal cell carcinomas (RCC) in rat. Affymetrix microarray technology will
be used to determine the gene dysregulation. |
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, in press, 2011, Toxicol. Sci.
- 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.
- Labenski, M.T., Fisher, A.A., Lo, H.H., Monks, T.J. and Lau, S.S. Protein electrophile-binding motifs: lysine rich proteins are preferential targets of quinones. Drug Metab. and Disp., 37: 1211-1218, 2009.
- 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.
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Past and present staff
Present
Graduate Students
Ryan Canatsey | Owen Kinsky | Chris Kuhlman | Nick Mastrandrea | Jessica Sapiro | Kevin Xu
Present Postdoctoral Fellow
Tim Radabaugh
Research Associate
Alfred Gallegos
Clinical Faculty Mentee
Hussein Yassine
Current Undergraduate Students
Wesley Cai, Itzel Rojas, Audrey Shi, Kim Tham
Recent Past Staff
Martina Bowen | Jennifer Cohen | Ashley
Fisher | Chris Hattan | Mike Kimzey | Matt Labenski | Jean Lord-Garcia
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