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Lau Laboratory
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Chris Kuhlman
Education:
- Doctoral Candidate Pharmacology and Toxicology University of Arizona 2008-Present
- B.S. Chemistry University of California, Los Angeles 2006
Achievements:
- Caldwell Health Sciences Award 2011
- 3rd place Graduate Student Best Paper Competition, ASPET 2011
- ASPET Graduate Student Travel Award 2011
- SOT Graduate Student Travel Award 2011
- SOT Mechanisms Specialty Section Carl C. Smith Award Honorable Mention 2011
- NIEHS Toxicology and Toxicogenomics Training Program Predoctoral Trainee 2010-present
Professional Experience:
- Research and Development Chemist, Bachem California, Inc. 2008 - 2007
- Chemist I, Bachem California, Inc. 2007 - 2006
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Research Project:
Occupational exposure to the aromatic hydrocarbon benzene has been associated with bone marrow toxicity and increased incidence of acute myelogenous leukemia. Benzene is a common industrial solvent isolated from petroleum and used in the manufacture of a variety of consumer goods including plastic containers, toys, adhesives, dyes, solvents, and cleaning products. Despite extensive research, the exact molecular mechanisms responsible for the myelotoxic effects of benzene have yet to be fully elucidated. It has been established that benzene requires metabolism to induce its effects. Hepatic Cytochrome P450 enzymes convert benzene to various phenolic metabolites, including phenol (PHE), hydroquinone (HQ), catechol, and 1,2,4-benzenetriol. Though the majority of these phenolic metabolites are excreted in urine as glucuronide and sulfate conjugates, studies have demonstrated that the co-administration of PHE and HQ can produce myelotoxicity in rats similar to that observed following benzene exposure.
Bone marrow is an organ roughly equivalent in size to the liver. It contains approximately 90% of the body’s granulocytic leukocytes, white blood cells that among other substances release significant amounts of myeloperoxidase. Benzene induced bone marrow suppression has been suggested to result from myeloperoxidase mediated oxidation of HQ, leading to reactive intermediates 1,4-benzosemiquinone and 1,4-benzoquinone. These metabolites may either directly arylate tissue macromolecules and/or redox cycle with the concomitant formation of reactive oxygen species (ROS). Furthermore, 1,4-benzoquinone can undergo nucleophilic addition with glutathione (GSH), leading to the formation of various GSH conjugates whose redox properties indicate they are more chemically reactive than hydroquinone. In a study performed in Dr. Lau’s laboratory, these GS-HQ conjugates were identified in rat bone marrow following co-administration of hydroquinone and phenol.
Christopher’s project utilizes the immense proteomic tools available at the University of Arizona’s Proteomics Consortium to search for specific bone marrow proteins that may be targeted by reactive benzene metabolites. Such information could provide clues to the development of benzene-induced leukemia as well as potential biomarkers for early detection of toxicity. |
Publications:
- Lau, S.S., Kuhlman, C., Shawn B. Bratton S.B. and Monks, T.J. Role of Hydroquinone-Thiol Conjugates in Benzene-Mediated Toxicity. Chemico-Biol Int., 184: 212-217, 2010.
Abstracts:
- Phenol/Hydroquinone Reduces Lymphocyte Counts and Produces Quinol-Thioether- and 4-Hydroxy-2-nonenal-Modified Proteins: Implications for Benzene-Mediated Hematotoxicity. Kuhlman, C., Petersen, D.R., Monks, T.J., and Lau, S.S. The FASEB Journal, 25:620.13, 2011. (Third place in 2011 Graduate Student Best Paper Competition sponsored by the Divison of Toxicology, American Society of Pharmacology and Experimental Therapeutics, FASEB).
- Instability of Quinone Electrophile Adducts on Cysteine Residues: A Basis for the Preferential Detection of Covalent Modification of Lysines and Arginines. Kuhlman, C.L., Labenski, M.L., Fisher, A.A., Olenyuk, B.Z., Monks, T.J., and Lau, S.S. Toxicologist, 105, 341, 2011. (Awarded Honorable Mentions of Carl C. Smith Mechanisms Graduate Student Award of SOT).
- Hydroquinone-Thiol Conjugates and Benzene-Mediated Hematotoxicity. Kuhlman, C., Petersen, D.R., Bratton, S.B., Butterworth, M., Monks, T.J., and Lau, S.S. VIII International Symposium on Biological Reactive Intermediates Abstract Proceeding, Barcelona, Spain July 15-18, 2010.
- Hydroquinone-thiol conjugates and benzene-mediated hematotoxicity. Kuhlman, C., Petersen, D.R., Bratton, S.B., Butterworth, M., Monks, T.J. and Lau, S.S. Toxicologist, 104, 780, 2010.
- Biological activity of hydroquione thiol conjugates. Lau, S.S., Kuhlman, C., Fisher A. and Monks, T.J. Benzene 2009: Health Effects and Mechansims of Bone Marrow Toxicity, Munich, Germany, 2009.
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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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