Millson, Stefan - University of Lincoln

个人简介

I joined the University of Lincoln in 2014, and I am a Lecture in the School of Life Sciences. Before coming to Lincoln I was a postdoctoral researcher at the University of Sheffield, University College London and the holder of a Bogue fellowship at the Howard Hughes Medical Institute. The main focus of my research has been molecular genetic analysis of Heat Shock Protein 90 (Hsp90), a promiscuous molecular chaperone that is currently a promising cancer drug target since it is needed for the activation of many of the proteins that drive cancer progression. I setup the UK’s first high throughput yeast two-hybrid protein interaction screening facility (Millson et al. 2003) and then used this to perform the first genomic yeast two hybrid screen for Hsp90 interactions, based on identifying the subset of interactions that are reinforced by a mutation that arrest the Hsp90 chaperone cycle (Millson et al. 2005). I then went on to study whether Hsp90-dependent processes are affected by placing different isoforms of Hsp90 in yeast cells (Millson et al. 2007), as well as the different ligand binding discriminations of Hsp90 client proteins (Millson et al. 2008). Subsequently I initiated a project designed to see how readily drug resistance could arise by mutation to very highly conserved drug binding site on Hsp90 – acquired drug resistance being such a major problem in chemotherapy treatment. It focussed on the Hsp90 proteins of microbes that produce the Hsp90-targetting antibiotics radicicol and geldanamycin, since we suspected that these might have evolved a natural resistance to cancer drugs designed on the basis of the interactions made by these antibiotics within the ADP/ATP binding site of Hsp90(Prodromou et al. 2009; Millson et al. 2010; Millson et al. 2011). My latest research (Millson et al. 2014) has addressed the TORC1 regulation of heat shock transcription factor (Hsf1), specifically whether rapamycin - selective TORC1 inhibitor approved for certain treatments – is capable of counteracting the Hsf1 activation that occurs upon inhibition of Hsp90. This Hsf1 activation, causing an induction of anti-apoptotic (“prosurvival”) heat shock proteins, often compromises the effectiveness of the Hsp90 inhibitor drugs in cancer treatment. I am also involved in collaborative research on Hsp90 system co-chaperones and on the myosin folding chaperone UNC45. Subject Specialism Use of yeast as a model system to study molecular chaperone “drivers” of cancer. Qualifications PhD. Molecular Genetics — University of Greenwich, 2001 MSc. Molecular Biology — University of Greenwich, 1998 BSc (Hons). Biochemistry — Liverpool John Moores University, 1994 Professional Affiliations Institute of Biomedical Sciences — Fellow

研究领域

Cancer research Molecular Genetics Moleular chaperones Protein folding Yeast

近期论文

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Willhoft, Oliver and Kerr, Richard and Patel, Dipali and Zhang, Wenjuan and Al-Jassar, Caezar and Daviter, Tina and Millson, Stefan H. and Thalassinos, Konstantinos and Vaughan, Cara K. (2017) The crystal structure of the Sgt1-Skp1 complex: the link between Hsp90 and both SCF E3 ubiquitin ligases and kinetochores. Scientific Reports, 7. pp. 41626. ISSN: 2045-2322 Gomez-Escalante, Susana and Piper, Peter W. and Millson, Stefan H. (2017) Mutation of the Ser18 phosphorylation site on the sole Saccharomyces cerevisiae UCS protein, She4, can compromise high-temperature survival. Cell Stress and Chaperones, 22 (1). pp. 135-141. ISSN: 1355-8145 Millson, Stefan and van Oosten-Hawle, Patricija and Alkuriji, Mohammed A. and Truman, Andrew and Siderius, Marco and Piper, Peter W. (2014) Cdc37 engages in stable, S14A mutation-reinforced association with the most atypical member of the yeast kinome, Cdk-activating kinase (Cak1). Cell Stress and Chaperones, 19 (5). pp. 695-703. ISSN: 1355-8145 Millson, S. H. and Piper, P. W. (2014) Insights from yeast into whether the inhibition of heat shock transcription factor (Hsf1) by rapamycin can prevent the Hsf1 activation that results from treatment with an Hsp90 inhibitor. Oncotarget, 5 (13). pp. 5054-5064. ISSN: 1949-2553 Piper, Peter and Millson, Stefan (2012) Spotlight on the microbes that produce heat shock protein 90-targeting antibiotics. Open Biology, 2 (DEC). ISSN: 2046-2441 Millson, S. H. and Chuang, C.-H. and Roe, S. M. and Polier, S. and Solovieva, S. and Pearl, L. H. and Sim, T.-S. and Prodromou, C. (2011) Features of the Streptomyces hygroscopicus HtpG reveal how partial geldanamycin resistance can arise with mutation to the ATP binding pocket of a eukaryotic Hsp90. FASEB Journal, 25 (11). pp. 3828-3837. ISSN: 0892-6638 Piper, P. W. and Millson, S. H. (2011) Mechanisms of resistance to Hsp90 inhibitor drugs: a complex mosaic emerges. Pharmaceuticals, 4 (11). pp. 1400-1422. ISSN: 1424-8247 Millson, Stefan H. and Prodromou, Chrisostomos and Piper, Peter W. (2010) A simple yeast-based system for analyzing inhibitor resistance in the human cancer drug targets Hsp90α/β. Biochemical Pharmacology, 79. pp. 1581-1588. ISSN: 0006-2952 Li, Xingmin and Millson, Stefan and Coker, Raymond and Evans, Ivor (2009) A sensitive bioassay for the mycotoxin aflatoxin B 1, which also responds to the mycotoxins aflatoxin G 1 and T-2 toxin, using engineered baker's yeast. Journal of Microbiological Methods, 77 (9). pp. 285-291. ISSN: 0167-7012 Millson, Stefan H. and Nuttall, James M. and Mollapour, Mehdi and Piper, Peter W. (2009) The Hsp90/Cdc37p chaperone system is a determinant of molybdate resistance in Saccharomyces cerevisiae. Yeast, 26 (6). pp. 339-347. ISSN: 0749-503X Prodromou, Chrisostomos and Nuttall, James M. and Millson, Stefan H. and Roe, S. Mark and Sim, Tiow-Suan and Tan, Doreen and Workman, Paul and Pearl, Laurence H. and Piper, Peter W. (2009) Structural basis of the radicicol resistance displayed by a fungal Hsp90. Acs Chemical Biology, 4 (4). pp. 289-297. ISSN: 1554-8929 Millson, Stefan H. and Evans, Ivor Howell (2007) Multiple dextranases from the yeast Lipomyces starkeyi. Antonie Van Leeuwenhoek International Journal of General and Molecular Microbiology, 92. pp. 399-404. ISSN: 0003-6072 Truman, A. W. and Millson, S. H. and Nuttall, J. M. and Mollapour, M. and Prodromou, C. and Piper, P. W. (2007) In the yeast heat shock response, Hsf1 directed induction of Hsp90 facilitates the activation of the Slt2 (Mpk1) mitogen-activated protein kinase required for cell integrity. Eukaryotic Cell, 6 (4). pp. 744-752. ISSN: 1535-9778 Truman, Andrew W. and Millson, Stefan H. and Nuttall, James M. and Mollapour, Mehdi and Prodromou, Chrisostomos and Piper, Peter W. (2007) In the yeast heat shock response, Hsf1-directed induction of Hsp90 facilitates the activation of the Slt2 (Mpk1) mitogen-activated protein kinase required for cell integrity. Eukaryotic Cell, 6 (4). pp. 744-752. ISSN: 1535-9778 Li, Xingmin and Millson, Stefan H. and Coker, Raymond D. and Evans, Ivor H. (2006) Cloning and expression of Penicillium minioluteum dextranase in Saccharomyces cerevisiae and its exploitation as a reporter in the detection of mycotoxins. Biotechnology Letters, 28. pp. 1955-1964. ISSN: 0141-5492 Truman, Andrew W. and Millson, Stefan H. and Nuttall, James M. and King, Victoria and Mollapour, Mehdi and Prodromou, Chrisostomos and Pearl, Laurence H. and Piper, Peter W. (2006) Expressed in the yeast saccharomyces cerevisiae, human ERK5 Is a client of the Hsp90 chaperone that complements loss of the Slt2p (Mpk1p) cell Integrity stress-activated protein kinase. Eukaryotic Cell, 5 (11). pp. 1914-1924. ISSN: 1535-9778 Phelan, John P. and Millson, Stefan H. and Parker, Peter J. and Piper, Peter W. and Cooke, Frank T. (2006) Fab1p and AP1 are required for trafficking of endogenously ubiquitylated cargoes to the vacuole lumen in S. cerevisiae. Journal of Cell Science, 119. pp. 4225-4234. ISSN: 0021-9533 Mollapour, Mehdi and Phelan, Oohn P. and Millson, Stefan H. and Piper, Peter W. and Cooke, Frank T. (2006) Weak acid and alkali stress regulate phosphatidylinositol bisphosphate synthesis in Saccharomyces cerevisiae. Biochemical Journal, 395 (1). pp. 73-80. ISSN: 0264-6021 Millson, Stefan H. and Truman, Andrew W. and King, Victoria and Prodromou, Chrisostomos and Pearl, Laurence H. and Piper, Peter W. (2005) A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpk1p). Eukaryotic Cell, 4 (5). pp. 849-860. ISSN: 1535-9778 Hu, Bin and Liao, Chunyan and Millson, Stefan H. and Mollapour, Mehdi and Prodromou, Chrisostomos and Pearl, Laurence H. and Piper, Peter W. and Panaretou, Barry (2005) Qri2/Nse4, a component of the essential Smc5/6 DNA repair complex: Nse4, an essential cell cycle protein. Molecular Microbiology, 55 (6). pp. 1735-1750. ISSN: 0950-382X Millson, Stefan H. and Truman, Andrew W. and King, Victoria and Prodromou, Crisostomos and Pearl, Lawrence H. and Piper, Peter W. (2005) A two-hybrid screen of the yeast proteome for Hsp90 interactors uncovers a novel Hsp90 chaperone requirement in the activity of a stress-activated mitogen-activated protein kinase, Slt2p (Mpk1p). Eukaryotic Cell, 4 (5). pp. 849-860. ISSN: 1535-9778 Piper, Peter W. and Millson, Stefan H. and Mollapour, Mehdi and Panaretou, Barry and Siligardi, Giuliano and Pearl, Laurence H. and Prodromou, Chrisostomos (2003) Sensitivity to Hsp90-targeting drugs can arise with mutation to the Hsp90 chaperone, cochaperones and plasma membrane ATP binding cassette transporters of yeast. European Journal of Biochemistry, 270 (23). pp. 4689-4695. ISSN: 0014-2956 Millson, S. H. and Truman, A. W. and Piper, P. W. (2003) Vectors for N- or C-terminal positioning of the yeast Gal4p DNA binding or activator domains. BioTechniques, 35 (1). pp. 60-64. ISSN: 0736-6205 Piper, P. W. and Panaretou, B. and Millson, S. H. and Trumana, A. and Mollapour, M. and Pearl, L. H. and Prodromou, C. (2003) Yeast is selectively hypersensitised to heat shock protein 90 (Hsp90)-targetting drugs with heterologous expression of the human Hsp90Î², a property that can be exploited in screens for new Hsp90 chaperone inhibitors. Gene, 302 (1-2). pp. 165-170. ISSN: 0378-1119 Piper, Peter W. and Panaretou, Barry and Millson, Stefan H. and Trumana, Andrew and Mollapour, Mehdi and Pearl, Laurence H. and Prodromou, Chrisostomos (2003) Yeast is selectively hypersensitised to heat shock protein 90 (Hsp90)-targetting drugs with heterologous expression of the human Hsp90β, a property that can be exploited in screens for new Hsp90 chaperone inhibitors. Gene, 302 (1-2). pp. 165-170. ISSN: 0378-1119