Our research interests focus on two main areas. In one, we investigate the mechanisms by which cells acquire, distribute, utilize and regulate the essential trace elements copper (Cu) and iron (Fe). These metal ions play important roles in neuropeptide maturation, energy generation, chromatin remodeling, signaling, protection from free radicals and other functions in growth, development and fungal infection. Another focus is on understanding how the Heat Shock Transcription Factor (HSF) functions to activate the expression of stress genes, encoding protein chaperones. Understanding the mechanisms by which HSF is activated has important implications in the treatment of diseases associated with protein misfolding. Our studies make use of model systems that include the baker's yeast, Saccharomyces cerevisiae, the opportunistic pathogenic yeast, Candida glabrata, fruit flies, cultured cells and mice.
Puig, S., Vergara, S.V. and Thiele, D.J. (2008) Cooperation of two mRNA-Binding Proteins Drives Metabolic Adaptation to Iron Deficiency. Cell Metabolism 7: 555-564.
Kim, B-E., Nevitt, T. and Thiele, D.J. (2008) Mechanisms for Copper Acquisition, Distribution and Regulation. Nature Chemical Biology 4:176-185.
Rees, E.M. and Thiele, D.J. (2007) Identification of a vacuole-associated metalloreductase and its role in CTR2-mediated intracellular copper mobilization. J. Biol. Chem. 282: 21629-21638.
Turski, M. L. and Thiele, D. J. (2007) Drosophila Ctr1A functions as a copper transporter essential for development. J. Biol. Chem. 282: 24017-24026.
Nose, Y., Kim, B., Thiele, D.J. (2006) Ctr1 Drives Intestinal Copper Absorption and is Essential for Growth, Iron Metabolism and Neonatal Cardiac Function. Cell Metabolism 4: 1-10.
Selvaraj, A., Balamurugan, K., Yepiskoposyan, H., Zhou, H., Egli, D., Georgiev, O., Thiele, D. J. and Schaffner, W. (2005). Metal-responsive transcription factor (MTF-1) handles both extremes, copper load and copper starvation, by activating different genes. Genes and Development 19: 891-896.
Hahn, J.-S., Neef, D. and Thiele, D. J. (2006) A Stress Regulatory Network for Coordinated Activation of Proteasome Expression Mediated by Heat Shock Transcription Factor. Molecular Microbiology 60: 240-251.
Park, K.-W., Hahn, J.S., Fan, Q., Thiele, D.J. and Li, L. (2006) De Novo Appearance and "Strain" Formation of Yeast Prion [PSI+] Are Regulated By the Heat Shock Transcription Factor. Genetics 173: 35-47.
Anckar, J., Hietakangas, V., Denessiouk, K., Thiele, D.J., Johnson, M.S. and Lea Sistonen, L. (2006) Inhibition of DNA binding by differential sumoylation of heat shock factors. Molecular and Cellular Biology 26: 955-964.
Puig, S., Askeland, E. and Thiele, D.J. (2005) Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation. Cell 120: 99-110.