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Lau Laboratory
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Christopher M. Hattan Ph.D.
Education:
- Ph.D. Medicinal Chemistry The University of Iowa 2008
- M.S. Physical Chemistry Illinois State University 2003
- B.S. Chemistry Illinois State University 2000
Achievements:
- NIEHS Human Genes and the Environment Research (HuGER) Training Program Postdoctoral Trainee 2009-2011
- NIEHS Toxicology and Toxicogenomics Training Program Postdoctoral Trainee 2008-2009
- University of Iowa College of Pharmacy Dissertation Fellowship
Professional Experience:
- Graduate Research Assistant, Division of Medicinal and Natural Products Chemistry, The University of Iowa 2004-2008
- Graduate Teaching Student, Illinois State University 2000-2003
- Intern, Caterpillar, Inc. 1998-2000
- Curriculum Vitae
Mentee:
Itzel Rojas |
Research Projects:
MALDI Imaging
Cancers utilize signaling pathways which often cross-talk. This enables them to evade the effects of new therapeutic agents to a particular target. One such cancer is prostate cancer. The key to customized treatments for prostate cancer is to establish diagnostic technologies that not only recognize specific proteins, but major protein pathways critical to disease progression. Biomarkers linked to prostate cancer progression and outcome have been described but not validated as clinical targets. Our consortium brings together expertise from various scientific disciplines including a state of the art mass spectrometer, innovations in cancer diagnostics, and MALDI imaging.
Utilizing LNCaP cells, a human prostate cancer cell line, a model eukaryotic initiation factor 4E binding protein 1 (4EBP1), a protein involved in the PI3K/AKT and mTOR signaling pathways, was selected as a potential biomarker. 4EBP1 was known to be phosphorylated during prostate cancer progression. An immunoprecipitation of 4EBP1, was analyzed by MALDI and western blotting to demonstrate phosphorylation. Comparison of untreated and drug-treated LNCaP cells yields information about levels of 4EBP1 phosphorylation. SDS-PAGE allowed for the separation 4EBP1 from other LNCaP proteins so trypsin digestion could be carried out for LC-MS/MS analysis. MALDI Imaging and immunohistochemical staining on prostate cancer tissue allowed for establishing protein localization in tissue at the subcellular level.
MALDI MS of 4EBP1 and phosphorylated Isoforms
Mitochondrial Targeted Prodrugs
Mitochondria are the major cellular source of reactive oxygen species and also play a central role in the life and death of cells; hence, there is considerable contemporary interest in targeting antioxidant compounds to mitochondria. A strategy to exploit the high negative internal potential of mitochondria allows targeting of lipophilic cationic antioxidants and the unique mitochondrial expression of enzymes to catalyze the release of drugs from prodrugs. Recently reported is the successful mitochondrial targeting of alkanoic- and alkenoic-acid-based prodrugs of phenolic and thiol antioxidants; these compounds are biotransformed by the fatty acid β-oxidation pathway to release antioxidant methyl-substituted phenols or methimazole. 3-(2,6-Dimethylphenoxy)propanoic acid and 3-(2,6-dimethylphenoxy)acrylic acid as well as 3- and 5-(1-methyl-1H-imidazol-2-ylthio)alkanoic acids conferred significant cytoprotection against hypoxia-reoxygenation injury in isolated rat cardiomyocytes. These studies also showed that the medium-chain acyl-CoA dehydrogenase apparently imposes significant structural limitations on substrates. To bypass this limitation, (E)-3-(2,6-dimethylphenoxy)acrylic acid, which was predicted to be a substrate for enoyl-CoA hydratase after conversion to its CoA thioester, was prepared and tested and was found to undergo a much higher rate of biotransformation than the alkanoic acid-based analog. We this in mind we are exploring the synthesis and in vitro study of 3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid.
Methimazole and Prodrugs (A) with Synthesis of 3-(1-methyl-1H-imidazol-2ylthio)acrylic Acid (B)
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Publications:
- Hattan, C.M., Shojaie, J., Lau, S.S. and Anders, M.W. Synthesis of 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic acid and (E)-3-(1-Methyl-1H-imidazol-2-ylthio)acrylic acid, in press, 2011, Synth. Commun.
Abstracts:
- MS-Based Tissue and Drug Imaging to Monitor 4EBP1 Phosphorylation Status and Drug-Induced Dephosphorylation in Prostate Cancer. Mastrandrea, N.J., Hattan, C., Gard, J.M.C., Nagle, T.J. Monks, T.J. and Lau, S.S. The FASEB Journal, 25:620.2, 2011.
- MALDI Imaging of Prostate Cancer Tissue Toward Validation of Biomarker Identification. Hattan, C., Mastandrea, N.J., Gard, J.M.M.C., Nagle, R., Monks, T.J., and Lau, S.S. Toxicologist, 105, 845, 2011.
- MALDI imaging of prostate cancer tissue toward validation of biomarker identification. Hattan, C., Leinweber, B., Nagle R., Gard, J., Pestano, G., Miller, P., Froehlich, J., Shi, G., Kruppa, G., Tsaprailis, G. and Lau, S.S. J. Am. Soc. Mass. Spec., Poster number WPG179, 20(5S), S94, 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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