Liviu M. Mirica, Ph.D.

Assistant Professor
Chemistry

Biochemistry, Biophysics, and Structural Biology Program

  • 935-3464

  • 1134

  • 425 McMillen Chemistry Labs

  • mirica@wustl.edu

  • http://www.chemistry.wustl.edu/faculty/mirica

  • Alzheimer’s disease, bioinorganic chemistry, drug design, enzymology, histone modification, redox processes

  • Development of specific inhibitors of histone demethylases; design of therapeutic and imaging chemical agents for Alzheimer's disease

Research Abstract:

Our research interests are focused on using chemical synthesis to develop specific inhibitors of histone demethylases and to design therapeutic and imaging chemical agents for Alzeimer’s disease. By nature, this work is highly interdisciplinary, benefiting from input from biochemists and inorganic chemists, organic and medicinal chemists. A collaborative approach will help attack the problems from multiple angles and thus allow for a detailed understanding of the underlying chemical and biochemical processes. The proposed studies are expected to attract graduate students with different research interests and to provide them with a broad knowledge base.

Histone Demethylases. Non-heme iron enzymes catalyze a wide range of oxidation and oxygenation reactions that have environmental, pharmaceutical, and medical significance. These enzymes, although exhibit a similar overall fold, exhibit different substrate specificity. This project aims to design and synthesize specific inhibitors of non-heme iron enzymes by taking advantage of the enzyme’s substrate specificity. Of particular interest are histone demethylases, a new class of enzymes that play an important role in regulating transcription and epigenetic inheritance. The developed inhibitors could be used as tools for studying the role of histone demethylases in cell function and development. Insights into the specificity of these enzymes will provide opportunities to advance therapeutics related to stem cell technology and cancer treatment.
Amyloid b Peptides in Alzheimer’s Disease. Alzheimer’s Disease (AD) is the most common neurodegenerative disease. Presently around five million people are diagnosed with AD in the US and the number is expected to reach fourteen million by 2050. The brains of patients with AD are characterized by the deposition of amyloid b (Ab) peptide plaques, which accumulate unusually high concentrations of copper, iron, and zinc. We are interested in the interaction of transition metal ions with Ab peptides and the role of metal ions in amyloid plaque and reactive oxygen species (ROS) formation. Additionally, a novel bifunctional strategy will be used to develop inhibitors of Ab peptide aggregation and imaging agents for Ab aggregates, which could provide improved strategies for the prevention, diagnosis, and treatment of AD.

Selected Publications:

Mirica LM, McCusker KP, Munos JW, Liu HW, Klinman JP. Probing the Nature of Reactive Fe/O2 Intermediates in Non-Heme Iron Enzymes through 18O Kinetic Isotope Effects. J. Am. Chem. Soc. 2008 130: 8122.

Mirica LM, Klinman JP. The Nature of O2 Activation by the Ethylene-Forming Enzyme ACC Oxidase. Proc. Natl. Acad. Sci. U. S. A. 2008 105:1814.

Mirica LM, Rudd DJ, Vance M, Solomon EI, Hedman B, Hodgson KO, Stack TDP. mu-eta2:eta2-peroxodicopper(II) complex with a secondary diamine ligand: a functional model of tyrosinase. J. Am. Chem. Soc. 2006 128:2654.

Mirica LM, Vance M, Rudd DJ, Hedman B, Hodgson KO, Solomon, EI, Stack TDP. Tyrosinase Reactivity in a Model Complex: an Alternative Hydroxylation Mechanism. Science 2005 308:1890.

Mirica LM, Vance M, Rudd DJ, Hedman B, Hodgson KO, Solomon EI, Stack TDP. A Stabilized m-h2:h2-Peroxodicopper(II) Complex with a Secondary Diamine Ligand and Its Tyrosinase-like Reactivity. J. Am. Chem. Soc. 2002 124:9332.

Last Updated: 8/4/2011 11:04:25 AM

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