Professor Carl Smythe
School of Biosciences
Chair in Cell Biology
Director of the Mass Spectrometry Centre
+44 114 222 4643
Full contact details
School of Biosciences
E03a Florey Building
Firth Court
Western Bank
91Ö±²¥
S10 2TN
- Profile
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- 2002 – present: Professor of Cell Biology, School of Biosciences, University of 91Ö±²¥
- 2004 – 2006: Head of Department, Department of Biomedical Science, University of 91Ö±²¥
- 1992 – 2002: Principal Investigator at MRC Protein Phosphorylation Unit, University of Dundee
- 1989 – 1992: American Cancer Society Senior Research Fellow, University of California, San Diego
- 1985 – 1989: British Diabetic Association postdoctoral research assistant at MRC Protein Phosphorylation Group at University of Dundee
- 1981 – 1985: PhD Department of Biochemistry, Trinity College, University of Dublin
- Research interests
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Chromosome integrity
Chromosomes in eukaryotes control their environment to ensure that genomic integrity is maximised. We are interested in understanding mechanisms of genomic integrity operating at the molecular and cellular level, and determining the consequences when they fail.
Cellular surveillance systems and their role in healthy aging
Research in our laboratory uses molecular cell biology approaches to understand quality control or surveillance mechanisms that operate in cells to ensure fidelity of function, the consequences when they fail, and how they may be exploited to ameliorate disease.
Examples include the replication checkpoint, which operates to ensure that cells experiencing replication stress, can evoke appropriate DNA damage responses, reschedule cell cycle events, or initiate apoptosis, and quality control systems regulating processes involving RNA homeostasis, such as nonsense-mediated decay (NMD), histone mRNA decay (HD), and telomere stability.
We utilise a variety of disease cell models in mechanistic studies and utilise whole genome and new chemical entity (NCE) screening together with mass spectrometry and imaging techniques, coupled with in vitro assays, to synergistically probe both biological and NCE function.
Our chemical biology work focuses on exploring the use of ruthenium co-ordination complexes to explore novel chemical space affecting pathways of interest, as well as novel indole polycyclic derivatives that block NMD.
Our focus is to identify potential new therapeutic targets in relevant disease models, and our work on the replication checkpoint has identified a number of proteins and /or pathways which are of interest.
Future directions
A key focus concerns the functional characterisation of the DNA /RNA helicase Upf1 which acts pleiotropically to regulate NMD, HD and telomere integrity. We have identified a novel NMD inhibitor which, importantly, does not affect histone mRNA regulation or telomere integrity.
We aim to utilise our expertise in genomic integrity and mass spectrometry to identify the target of this inhibitor as a potential therapeutic strategy for the treatment of nonsense mutation-associated disease.
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- . Org. Biomol. Chem., 14(5), 1559-1563.
- . Seminars in Cancer Biology, 35, S276-S304.
- . Chemistry - A European Journal, 21(25), 9185-9197.
- . Angew Chem Int Ed Engl, 53(13), 3367-3371.
- . NAT CHEM, 1(8), 662-667.
- . Journal of Cell Biology, 179(7), 1385-1398.
- . Hum Mol Genet, 13(23), 2937-2945.
- . JOURNAL OF CELL BIOLOGY, 154(5), 913-923.
- . PLoS ONE, 10(10).
All publications
Journal articles
- . Heliyon, 9(11), e22365-e22365.
- . Cancers, 15(1).
- . PeerJ, 10, e13508.
- . Angew Chem Weinheim Bergstr Ger, 134(27), e202117449.
- . Angewandte Chemie International Edition, 61(27).
- . Biomolecules, 10(2).
- . Journal of the American Chemical Society.
- . ACS Nano, 13(5), 5133-5146.
- . Journal of the American Chemical Society, 141(7), 2925-2937.
- . Chemical Communications.
- . Molecules, 23(12).
- . Crystal Growth and Design, 18(11), 7199-7206.
- . Bioconjugate Chemistry.
- . Chemical Communications, 54(30), 3735-3738.
- . Dalton Transactions, 47(14), 4931-4940.
- . Chemical Communications, 54(15), 1849-1852.
- . Analytical Chemistry, 89(22), 12087-12093.
- . Chemical Science, 9, 841-849.
- . Journal of the American Chemical Society, 139(44), 15907-15913.
- . Chemical Communications, 53, 12672-12675.
- . Angewandte Chemie International Edition, 129(41), 12802-128007.
- . Chemistry - A European Journal, 22(17), 5996-6000.
- . Org. Biomol. Chem., 14(5), 1559-1563.
- . Seminars in Cancer Biology, 35, S276-S304.
- . Chemistry - A European Journal, 21(33), 11865-11871.
- . Chemistry - A European Journal, 21(25), 9185-9197.
- . Chemistry - A European Journal, 20(43), 14004-14011.
- . Angew Chem Int Ed Engl, 53(13), 3367-3371.
- . Chemical Science.
- . Chembiochem, 12(6), 877-880.
- . EMBO J, 29(17), 2930-2942.
- . NAT CHEM, 1(8), 662-667.
- . Journal of Cell Biology, 180(4), 843-843.
- . Journal of Cell Science, 121(5), 706-716.
- . Journal of Cell Biology, 179(7), 1385-1398.
- . Hum Mol Genet, 13(23), 2937-2945.
- . J Cell Biol, 163(2), 231-236.
- . Biochemical Journal, 368(2), 507-516.
- . MOLECULAR BIOLOGY OF THE CELL, 13(9), 3344-3354.
- . JOURNAL OF CELL BIOLOGY, 154(5), 913-923.
- . Current Biology, 10(17), 1075-1078.
- . JOURNAL OF BIOLOGICAL CHEMISTRY, 275(32), 24284-24293.
- . ONCOGENE, 18(48), 6707-6713.
- . Biochemical Society Transactions, 27(3), A97-A97.
- . JOURNAL OF CELL BIOLOGY, 144(2), 225-240.
- . EXPERIMENTAL CELL RESEARCH, 241(1), 12-22.
- NEP-B78 is a novel integral nuclear membrane protein involved in nuclear envelope precursor vesicle targeting to chromatin.. MOLECULAR BIOLOGY OF THE CELL, 8, 608-608.
- . CURRENT BIOLOGY, 7(1), 71-80.
- Activation of the Xenopus cyclin degradation machinery by full-length cyclin A. JOURNAL OF CELL SCIENCE, 109, 1071-1079.
- Isolation and characterisation of a uniquely regulated threonine, tyrosine phosphatase (TYP 1) which inactivates ERK2 and p54(jnk). ONCOGENE, 11(12), 2553-2563.
- XCL100, AN INDUCIBLE NUCLEAR MAP KINASE PHOSPHATASE FROM XENOPUS-LAEVIS - ITS ROLE IN MAP KINASE INACTIVATION IN DIFFERENTIATED CELLS AND ITS EXPRESSION DURING EARLY DEVELOPMENT. JOURNAL OF CELL SCIENCE, 108, 2885-2896.
- THE ROLE OF B-TYPE LAMINS IN THE ASSEMBLY OF A REPLICATION COMPETENT NUCLEUS. JOURNAL OF CELLULAR BIOCHEMISTRY, 123-123.
- IDENTIFICATION OF NOVEL REGULATORY EVENTS IN NUCLEAR-ENVELOPE REASSEMBLY USING XENOPUS EGG EXTRACTS. JOURNAL OF CELLULAR BIOCHEMISTRY, 94-94.
- MONOCLONAL-ANTIBODIES TO STRUCTURAL ELEMENTS OF AMPHIBIAN NUCLEAR ENVELOPES. JOURNAL OF CELLULAR BIOCHEMISTRY, 90-90.
- THE HUMAN CL100 GENE ENCODES A TYR/THR-PROTEIN PHOSPHATASE WHICH POTENTLY AND SPECIFICALLY INACTIVATES MAP KINASE AND SUPPRESSES ITS ACTIVATION BY ONCOGENIC RAS IN XENOPUS-OOCYTE EXTRACTS. ONCOGENE, 8(7), 2015-2020.
- . Molecular and Cellular Biology, 12(7), 3216-3223.
- . CELL, 68(4), 787-797.
- , 449-468.
- . EUROPEAN JOURNAL OF BIOCHEMISTRY, 200(3), 625-631.
- . CELL, 65(2), 209-217.
- . EUROPEAN JOURNAL OF BIOCHEMISTRY, 189(2), 243-249.
- . EUROPEAN JOURNAL OF BIOCHEMISTRY, 189(1), 199-204.
- . EUROPEAN JOURNAL OF BIOCHEMISTRY, 183(1), 205-209.
- . EUROPEAN JOURNAL OF BIOCHEMISTRY, 176(2), 391-395.
- . EMBO JOURNAL, 7(9), 2681-2686.
- . EUROPEAN JOURNAL OF BIOCHEMISTRY, 169(3), 497-502.
- . Cell Death & Disease, 15(12).
- . Molecules, 29(9), 2113-2113.
- . Journal of the American Chemical Society.
- . Chemistry – A European Journal.
- . Journal of the American Chemical Society.
- . Chem. Commun., 50(93), 14494-14497.
- , 161-186.
- . PLoS ONE, 10(10).
Chapters
Conference proceedings papers
- Analysis of the Mechanism of DNA Damage and Replication Arrest-induced Histone mRNA DecayPornpen Panomwan*and Carl Smythe. FASEB JOURNAL, Vol. 29
- Analysis of the mechanism of DNA damage and replication arrest-induced histone mRNA decay. FEBS JOURNAL, Vol. 281 (pp 65-65)
- Ruthenium(II) polypyridyl complexes: In cellulo DNA binding and cytotoxicity. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 241
- Are multiple checkpoint mediators involved in a checkpoint linking histone gene expression with DNA replication?. BIOCHEMICAL SOCIETY TRANSACTIONS, Vol. 35 (pp 1369-1371)
- . BREAST CANCER RESEARCH, Vol. 8 (pp S5-S6)
- The role of mitotic vesicles in the nuclear assembly. CELLULAR & MOLECULAR BIOLOGY LETTERS, Vol. 7(2) (pp 299-299)
- . EMBO JOURNAL, Vol. 19(15) (pp 3918-3931)
- Research group
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Key collaborators
- Prof Iain Coldham, Dept of Chemistry, University of 91Ö±²¥
- Dr James Thomas, Dept of Chemistry, University of 91Ö±²¥
- Dr Sarah Danson, Dept of Oncology, University of 91Ö±²¥
- Dr Ferdinando Di Cunto, Department of Genetics, Biology& Biochemistry, University of Torino.
- Grants
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- Cystic Fibrosis Trust
- Yorkshire Cancer Research
- Royal Thai Higher Education Commission
- Malaysia Trust Council (Majlis Amanah Rakyat)
- Teaching activities
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Undergraduate and postgraduate taught modules
Undergraduate:
- BMS109-106 Pathobiology
- BMS379 Cancer Biology (Co-ordinator)
Masters (MSc):
- BMS6057 Cancer Biology (Co-ordinator)