An increasing number of diseases are associated with misfolding of proteins , which can lead to the acummulation in vital organs of amorphous protein aggregates or ordered amyloid fibrils. These diseases include conditions such as Alzheimer's, Huntington's, Parkinson's and transmissible spongiform encephalopathies (TSEs). TSEs, such as mad cow disease in cattle, scrapie in sheep, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS) and fatal familial insomnia (FFI) in humans, are associated with the conversion of a cellular plasma membrane glycoprotein, the prion protein , to an altered form that is suggested to be both the infectious agent and the cause of rapid neurodegeneration . Structural studies have established that prion conversion from the cellular healthy conformation to the disease-associated form involves a major refolding of the prion protein that results in amorphous aggregates or ordered amyloid fibrils.
In my research group we are interested in understanding the molecular mechanism of prion conversion, studying the folding and structure of prions both in solution and in association with lipid membranes , the aggregation and fibrillization of prions, and the mechanisms of neurodegeneration and neuronal death.
Research Themes: Molecular and Cell Systems
DPhil Oxford University 1993
- Kaufmann, Timothy J., Harrison, Paul Michael, Richardson, Magnus J. E., Pinheiro, Teresa J. T., Wall, Mark J., 2016. Intracellular soluble a-synuclein oligomers reduce pyramidal cell excitability. The Journal of Physiology, 594 (10), pp. 2751-2772
- Monteiro, João P., Martins, André F., Nunes, Cláudia, Morais, Catarina M., Lúcio, Marlene, Reis, Salette, Pinheiro, Teresa J. T., Geraldes, Carlos F. G. C., Oliveira, Paulo J., Jurado, Amália S., 2013. A biophysical approach to menadione membrane interactions: Relevance for menadione-induced mitochondria dysfunction and related deleterious/therapeutic effects. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1828 (8), pp. 1899-1908
- Lu, Jin, Stewart, Alan J, Sleep, Darrell, Sadler, P. J., Pinheiro, Teresa J. T., Blindauer, Claudia A., 2012. A molecular mechanism for modulating plasma Zn speciation by fatty acids. Journal of the American Chemical Society, Vol.134 (No.3), pp. 1454-1457
- Lu, Jin, Stewart, Alan J., Sadler, P. J., Pinheiro, Teresa J. T., Blindauer, Claudia A., 2012. Allosteric inhibition of cobalt binding to albumin by fatty acids : implications for the detection of myocardial ischemia. Journal of Medicinal Chemistry, Vol.55 (No.9), pp. 4425-4430
- Hill, Andrew Francis, Graham, James F., Kurian, Dominic, Agarwal, Sonya, Toovey, Lorna, Hunt, Lawrence, Kirby, Louise, Pinheiro, Teresa J. T., Banner, Steven J., Gill, Andrew C., 2011. Na+/K+-ATPase Is Present in Scrapie-Associated Fibrils, Modulates PrP Misfolding In Vitro and Links PrP Function and Dysfunction. PLoS One, Vol.6 (No.11)
- Monteiro, João P., Martins, André F., Lúcio, Marlene, Reis, Salette, Pinheiro, Teresa J. T., Geraldes, Carlos F. G. C., Oliveira, Paulo J., Jurado, Amália S., 2011. Nimesulide interaction with membrane model systems : are membrane physical effects involved in nimesulide mitochondrial toxicity?. Toxicology in Vitro, Vol.25 (No.6), pp. 1215-1223
- Sanghera, Narinder, Correia, Bruno E. F. S, Correia, Joana R. S., Ludwig, Christian, Agarwal, Sonya, Nakamura, Hironori K., Kuwata, Kazuo, Samain, Eric, Gill, Andrew C., Bonev, Boyan B., Pinheiro, Teresa J. T., 2011. Deciphering the molecular details for the binding of the prion protein to main ganglioside GM1 of neuronal membranes. Chemistry & Biology, Vol.18 (No.11), pp. 1422-1431
- Grabenauer, Megan, Wyttenbach, Thomas, Sanghera, Narinder, Slade, Susan E., Pinheiro, Teresa J. T., Scrivens, James H., Bowers, Michael T., 2010. Conformational stability of Syrian hamster prion protein PrP(90-231). Journal of the American Chemical Society, Vol.132 (No.26), pp. 8816-8818
- Gill, Andrew C., Agarwal, Sonya, Pinheiro, Teresa J. T., Graham, James F., 2010. Structural requirements for efficient prion protein conversion : cofactors may promote a conversion-competent structure for PrPC. Prion, 4 (4), pp. 235-243
- Robinson, Philip J., Pinheiro, Teresa J. T., 2010. Phospholipid composition of membranes directs prions down alternative aggregation pathways. Biophysical Journal, Vol.98 (No.8), pp. 1520-1528
- Graham, James F., Agarwal, Sonya, Kurian, Dominic, Kirby, Louise, Pinheiro, Teresa J. T., Gill, Andrew C., 2010. Low density subcellular fractions enhance disease-specific prion protein misfolding. Journal of Biological Chemistry, Vol.285 (No.13), pp. 9868-9880
- Mayerhofer, Peter U., Cook, Jonathan P., Wahlman, Judit, Pinheiro, Teresa J. T., Moore, Katherine A. H., Lord, Mike, Johnson, Arthur E., Roberts, L. M. (Lynne M.), 2009. Ricin A chain insertion into endoplasmic reticulum membranes is triggered by a temperature increase to 37 degrees C. Journal of Biological Chemistry, Vol.284 (No.15), pp. 10232-10242
- Sanghera, Narinder, Swann, Marcus J., Ronan, Gerry, Pinheiro, Teresa J. T., 2009. Insight into early events in the aggregation of the prion protein on lipid membranes. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol.1788 (No.10), pp. 2245-2251
- Jenkins, David C., Pearson, David S., Harvey, Andrew, Sylvester, Ian D., Geeves, Michael A., Pinheiro, Teresa J. T., 2009. Rapid folding of the prion protein captured by pressure-jump. European Biophysics Journal, Vol.38 (No.5), pp. 625-635
- Robinson, Philip J., Pinheiro, Teresa J. T., 2009. The unfolding of the prion protein sheds light on the mechanisms of prion susceptibility and species barrier. Biochemistry, Vol.48 (No.36), pp. 8551-8558
- Hicks, Matthew R., Rullay, Atvinder K., Pedrido, Rosa, Crout, D. H. G., Pinheiro, Teresa J. T., 2008. Efficient synthesis of methanesulphonate-derived lipid chains for attachment of proteins to lipid membranes. Synthetic Communications, 38 (21), pp. 3726-3750
- Jenkins, David C., Sylvester, Ian D., Pinheiro, Teresa J. T., 2008. The elusive intermediate on the folding pathway of the prion protein. FEBS Journal, Vol.275 (No.6), pp. 1323-1335
- Lu, Jin, Stewart, Alan J., Sadler, P. J., Pinheiro, Teresa J. T., Blindauer, Claudia A., 2008. Albumin as a zinc carrier : properties of its high-affinity zinc-binding site. Biochemical Society Transactions, Vol.36 (No.6), pp. 1317-1321
- Cowan, Richard H., Davies, Rick A., Pinheiro, Teresa J. T., 2008. A screening system for the identification of refolding conditions for a model protein kinase, p38 alpha. Analytical Biochemistry, Vol.376 (No.1), pp. 25-38
- Sanghera, Narinder, Wall, Mark J., Venien-Bryan, Catherine, Pinheiro, Teresa J. T., 2008. Globular and pre-fibrillar prion aggregates are toxic to neuronal cells and perturb their electrophysiology. Biochimica et Biophysica Acta - Proteins and Proteomics, Vol.1784 (No.6), pp. 873-881
- Dear, Denise V., Young, Duncan S., Kazlauskaite, Jurate, Meersman, Filip, Oxley, David, Webster, Judith, Pinheiro, Teresa J. T., Gill, Andrew C., Bronstein, Igor, Lowe, Christopher R., 2007. Effects of post-translational modifications on prion protein aggregation and the propagation of scrapie-like characteristics in vitro. Biochimica et Biophysica Acta - Proteins and Proteomics, Vol.1774 (No.7), pp. 792-802
- Critchley, Peter, Kazlauskaite, Jurate, Eason, Robert, Pinheiro, Teresa J. T., 2002. Binding of prion proteins to lipid membranes. Biochemical and Biophysical Research Communications, 313 (3), pp. 559-567
- Sanghera, Narinder, Pinheiro, Teresa J. T., 2000. Unfolding and refolding of cytochrome c driven by the interaction with lipid micelles. Protein Science, Vol.9 (No.6), pp. 1194-1202
- Hilton, Gillian R., Thalassinos, Konstantinos, Grabenauer, Megan, Sanghera, Narinder, Slade, Susan E., Wyttenbach, Thomas, Robinson, Philip J., Pinheiro, Teresa J. T., Bowers, Michael T., Scrivens, James H., 2010. Structural analysis of prion proteins by means of drift cell and traveling wave ion mobility mass spectrometry. Asilomar Conference on Ion Spectroscopy, Pacific Grove, CA, October 16-20, 2009, Published in Journal of The American Society for Mass Spectrometry, pp. 845-854
- Pinheiro, Teresa J. T., 2006. The role of rafts in the fibrillization and aggregation of prions. COST Meeting on Protein - Lipid Interactions, Dubrovnik, Croatia, Oct 06-08, 2005, Published in Chemistry and Physics of Lipids, pp. 66-71
- Robinson, Philip J., Pinheiro, Teresa J. T., 2010. Growth of prion plaques and spongiform aggregates on lipid membranes. Prion, Landes Bioscience, pp. 178-179
Title | Funder | Award start | Award end |
---|---|---|---|
Selection of nucleic acid aptamers against defined oligomeric states of PrP and -synuclein. | University of Sheffield | 01 Aug 2012 | 31 Mar 2013 |
PCB Network (via Leeds) Smart nanoparticle sensors for detection & quantitation of prions and amyloid components | EPSRC | 14 Feb 2012 | 30 Apr 2012 |
Developing of a Microsecond Mixing Instrument for the Detection of Folding intermediates - Precursors of Amyloid Formation in Neurodegeneration | EPSRC | 01 Sep 2008 | 31 Aug 2011 |
CASE Agreement: Richard Cowan: Folding of Protein Kinases | AstraZeneca | 01 Oct 2005 | 30 Sep 2009 |
A Conformational Biosensor for Diagnosis of Prion Diseases. | BBSRC | 15 May 2006 | 14 May 2007 |
Structure, Stability & Molecular Interactions In Biological Systems | BBSRC | 01 Sep 2005 | 31 May 2006 |
Assisted protein folding: membrane protein translocation and assembly: Research Fship | Royal Society | 01 Oct 1995 | 30 Sep 2003 |
Assisted protein folding: membrane protein translocation and assembly: Research Fship | Royal Society | 01 Oct 1995 | 30 Sep 2003 |