Liviu Mirica, PhD

Associate Professor of Chemistry

Development of therapeutic and imaging chemical agents for Alzheimer’s disease; Design of specific inhibitors of histone demethylases Read More

Email: mirica@wustl.edu
Lab Phone: (314) 935-4991
Website: Mirica Lab
Lab Location: McMillen Chemistry Labs 425
Keywords: Alzheimer’s disease, bioinorganic chemistry, drug design, enzymology, histone modification, redox processes

Development of therapeutic and imaging chemical agents for Alzheimer’s disease; Design of specific inhibitors of histone demethylases

Our research interests are focused on using chemical synthesis to develop therapeutic and imaging chemical agents for Alzeimer’s disease and to design specific inhibitors of histone demethylases. 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.

Amyloid b Peptides in Alzheimer’s Disease. Alzheimer’s Disease (AD) is the most common neurodegenerative disease. The brains of patients with AD are characterized by the deposition of amyloid beta (Abeta) peptide plaques, which also accumulate unusually high concentrations of copper, iron, and zinc. We are interested in the interaction of transition metal ions with the Abeta peptides and the role of metal ions in amyloid plaque and reactive oxygen species (ROS) formation. Additionally, a novel bifunctional strategy is employed to develop both chemical agents that control Abeta aggregation, as well as imaging agents for various Abeta aggregates, including soluble Abeta oligomers. These novel compounds could lead to improved strategies for the prevention, treatment, and early diagnosis of AD.

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.”


Updated September 2015

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