The Thiele laboratory investigates two areas of biology. In one area, we study how Heat Shock Transcription Factor 1 (HSF1) senses the presence of misfolded proteins and other cellular stresses and activates the expression of genes that prevent protein aggregation and maintain cell function and viability. We use genetics, chemical and structural biology, cell biology, mouse models of human disease to solve fundamentally important questions on the role of HSF1 in health and disease. In another area we investigate how organisms acquire and detoxify copper and how these processes are accomplished and regulated by membrane transporters, signaling molecules, transcription factors and novel mechanisms. Our studies focus on the fungal pathogen Cryptococcus neoformans, on mouse models for mammalian copper metabolism, and at the host-pathogen interface in fungal pathogenesis.
Jaeger, A.M., Pemble IV, C.W., Sistonen, L. and Thiele, D.J. (2016) Structures of HSF2 reveal mechanisms for differential regulation of human heat-shock factors. Nature Structural & Molecular Biology 23: 147-154.
García-Santamarina, S. and Thiele, D.J. (2015) Copper at the Fungal Pathogen-Host Axis. Journal of Biological Chemistry 290:18945-18953.
Neef, D.W., Jaeger, A., Gomez-Pastor, R., Willmund, F., Frydman, J. and Thiele, D.J. (2014) A direct regulatory interaction between the cytosolic chaperone complex (TRiC/CCT) and the cytosolic stress-responsive transcription factor HSF1. Cell Reports 6:955-966.
Festa, R.A., Helsel, M.E., Franz, K.J. and Thiele, D.J. (2014) Exploiting Innate Immune Cell Activation of a Copper-Dependent Antimicrobial Agent during Infection. Cell Chemistry & Biology. 21: 977-987.
Öhrvik, H., Nose, Y. Wood, L.K., Kim, B.-E., Gleber, S.C., Ralle, M. and Thiele, D.J. (2013) Ctr2 regulates biogenesis of a cleaved form of the mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain. Proc. Natl. Acad. Sci. USA 110: 4279-4288.
Ding, C., Festa, R.A., Chen, Y.-L., Espart, A., Palacios, O., Espin, J., Capdevilla, M., Atrian, S. Heitman, J. and Thiele, D.J. (2013) Cryptococcus neoformans copper detoxification machinery is a critical fungal virulence factor. Cell Host & Microbe 13: 265-276.
Neef, D.W., Jaeger, A.M. and Thiele, D.J. (2011) HSF1 as a therapeutic target in neurodegenerative disease. Nature Reviews Drug Discovery 10: 930-944.