Smythe, Carl, Professor

Professor Carl Smythe

School of Biosciences

Chair in Cell Biology

Director of the Mass Spectrometry Centre

c.g.w.smythe@sheffield.ac.uk
+44 114 222 4643

E03a Florey Building, Firth Court

Full contact details

Professor Carl Smythe
School of Biosciences
E03a Florey Building
Firth Court
Western Bank
��«Ӱҵ
S10 2TN

Profile

2002 – present: Professor of Cell Biology, School of Biosciences, University of ��«Ӱҵ
2004 – 2006: Head of Department, Department of Biomedical Science, University of ��«Ӱҵ
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

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

Show: Featured publications All publications

Featured publications

Journal articles

Gotham VJB, Hobbs MC, Burgin R, Turton D, Smythe C & Coldham I (2016) . Org. Biomol. Chem., 14(5), 1559-1563.
Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin ARMR, Amin A, Aquilano K, Arbiser J, Arreola A, Arzumanyan A , Ashraf SS et al (2015) . Seminars in Cancer Biology, 35, S276-S304.
Ramu V, Gill M, Jarman P, Turton D, Thomas J, Das A & Smythe CG (2015) . Chemistry - A European Journal, 21(25), 9185-9197.
Baggaley E, Gill MR, Green NH, Turton D, Sazanovich IV, Botchway SW, Smythe C, Haycock JW, Weinstein JA & Thomas JA (2014) . Angew Chem Int Ed Engl, 53(13), 3367-3371.
Gill MR, Garcia-Lara J, Foster SJ, Smythe C, Battaglia G & Thomas JA (2009) . NAT CHEM, 1(8), 662-667.
Müller B, Blackburn J, Feijoo C, Zhao X & Smythe C (2007) . Journal of Cell Biology, 179(7), 1385-1398.
Bolderson E, Scorah J, Helleday T, Smythe C & Meuth M (2004) . Hum Mol Genet, 13(23), 2937-2945.
Feijoo C, Hall-Jackson C, Wu R, Jenkins D, Leitch J, Gilbert DM & Smythe C (2001) . JOURNAL OF CELL BIOLOGY, 154(5), 913-923.
Novodvorsky P, Watson O, Gray C, Wilkinson RN, Reeve S, Smythe C, Beniston R, Plant K, Maguire R, M. K. Rothman A , Elworthy S et al () . PLoS ONE, 10(10).

All publications

Journal articles

Rattajak P, Aroonkesorn A, Smythe C, Wititsuwannakul R & Pitakpornpreecha T (2023) . Heliyon, 9(11), e22365-e22365.
Acuña MI, Rubio AR, Martínez-Alonso M, Busto N, Rodríguez AM, Davila-Ferreira N, Smythe C, Espino G, García B & Domínguez F (2023) . Cancers, 15(1).
Chimplee S, Smythe C, Tipmanee V, Sukrong S & Kanokwiroon K (2022) . PeerJ, 10, e13508.
Gill MR, Jarman PJ, Hearnden V, Fairbanks SD, Bassetto M, Maib H, Palmer J, Ayscough KR, Thomas JA & Smythe C (2022) . Angew Chem Weinheim Bergstr Ger, 134(27), e202117449.
Gill MR, Jarman PJ, Hearnden V, Bassetto M, fairbanks SD, Palmer J, Ayscough KF, Thomas JA & Smythe C (2022) . Angewandte Chemie International Edition, 61(27).
Yodthong T, Kedjarune-Leggat U, Smythe C, Sukprasirt P, Aroonkesorn A, Wititsuwannakul R & Pitakpornpreecha T (2020) . Biomolecules, 10(2).
Saeed H, Sreedharan S, Jarman PJ, Archer SA, Fairbanks SD, Foxon SP, Auty AJ, Chekulaev D, Keane T, Meijer AJHM , Weinstein JA et al (2019) . Journal of the American Chemical Society.
Smitten KL, Southam HM, de la Serna JB, Gill MR, Jarman PJ, Smythe CGW, Poole RK & Thomas JA (2019) . ACS Nano, 13(5), 5133-5146.
Jarman P, Noakes F, Fairbanks S, Smitten K, Griffiths I, Saeed H, Thomas J & Smythe CG (2019) . Journal of the American Chemical Society, 141(7), 2925-2937.
Singh H, Sreedharan S, Tiwari K, Green N, Smythe C, Pramanik SK, Thomas JA & Das A (2018) . Chemical Communications.
Yodthong T, Kedjarune-Leggat U, Smythe C, Wititsuwannakul R & Pitakpornpreecha T (2018) . Molecules, 23(12).
Singh H, Sreedharan S, Tiwari R, Walther C, Smythe C, Pramanik SK, Thomas JA & Das A (2018) . Crystal Growth and Design, 18(11), 7199-7206.
Pramanik SK, Sreedharan S, Singh H, Khan M, Tiwari K, Shiras A, Smythe CGW, Thomas JA & Das A (2018) . Bioconjugate Chemistry.
Anila HA, Sreedharan S, Ali F, Smythe CG, Thomas JA & Das A (2018) . Chemical Communications, 54(30), 3735-3738.
Sreedharan S, Sinopoli A, Jarman PJ, Robinson D, Clemmet C, Scattergood PA, Rice CR, Smythe CGW, Thomas JA & Elliott PIP (2018) . Dalton Transactions, 47(14), 4931-4940.
Ali F, Aute S, Sreedharan S, Anila HA, Saeed HK, Smythe CG, Thomas JA & Das A (2018) . Chemical Communications, 54(15), 1849-1852.
Ali F, Sreedharan S, Ashoka AH, Saeed HK, Smythe CGW, Thomas JA & Das A (2017) . Analytical Chemistry, 89(22), 12087-12093.
Gill MR, Jarman PJ, Swagata H, Walker MG, Saeed HK, Thomas JA, Smythe CGW, Ramadan K & Vallis K (2017) . Chemical Science, 9, 841-849.
Sreedharan S, Gill M, Garcia E, Saeed HK, Robinson D, Byrne A, Cadby AJ, Keyes TE, Smythe CGW, Pellett P , Bernardino de la Serna J et al (2017) . Journal of the American Chemical Society, 139(44), 15907-15913.
Pramanik SK, Sreedharan S, Singh H, Green NH, Smythe C, Thomas J & Das A (2017) . Chemical Communications, 53, 12672-12675.
Saeed H, Jarman P, Archer S, Sreedharan S, Saeed I, Mckenzie L, Weinstein J, Buurma N, Smythe C & Thomas JA (2017) . Angewandte Chemie International Edition, 129(41), 12802-128007.
Walker M, Jarman P, Gill M, Tian X, Ahmad H, Reddy P, McKenzie L, Weinstein J, Meijer A, Battaglia G , Smythe C et al (2016) . Chemistry - A European Journal, 22(17), 5996-6000.
Gotham VJB, Hobbs MC, Burgin R, Turton D, Smythe C & Coldham I (2016) . Org. Biomol. Chem., 14(5), 1559-1563.
Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin ARMR, Amin A, Aquilano K, Arbiser J, Arreola A, Arzumanyan A , Ashraf SS et al (2015) . Seminars in Cancer Biology, 35, S276-S304.
Wragg A, Gill MR, McKenzie L, Glover C, Mowll R, Weinstein JA, Su X, Smythe C & Thomas JA (2015) . Chemistry - A European Journal, 21(33), 11865-11871.
Ramu V, Gill M, Jarman P, Turton D, Thomas J, Das A & Smythe CG (2015) . Chemistry - A European Journal, 21(25), 9185-9197.
Wragg A, Gill MR, Turton D, Adams H, Roseveare TM, Smythe C, Su X & Thomas JA (2014) . Chemistry - A European Journal, 20(43), 14004-14011.
Baggaley E, Gill MR, Green NH, Turton D, Sazanovich IV, Botchway SW, Smythe C, Haycock JW, Weinstein JA & Thomas JA (2014) . Angew Chem Int Ed Engl, 53(13), 3367-3371.
Gill M, Cecchin D, Walker MG, Mulla RS, Battaglia G, Smythe CG & Thomas JA (2013) . Chemical Science.
Gill MR, Derrat H, Smythe CGW, Battaglia G & Thomas JA (2011) . Chembiochem, 12(6), 877-880.
Bishop A, Lane R, Beniston R, Chapa-y-Lazo B, Smythe C & Sudbery P (2010) . EMBO J, 29(17), 2930-2942.
Gill MR, Garcia-Lara J, Foster SJ, Smythe C, Battaglia G & Thomas JA (2009) . NAT CHEM, 1(8), 662-667.
Müller B, Blackburn J, Feijoo C, Zhao X & Smythe C (2008) . Journal of Cell Biology, 180(4), 843-843.
Salpingidou G, Rzepecki R, Kiseleva E, Lyon C, Lane B, Fusiek K, Golebiewska A, Drummond S, Allen T, Ellis JA , Smythe C et al (2008) . Journal of Cell Science, 121(5), 706-716.
Müller B, Blackburn J, Feijoo C, Zhao X & Smythe C (2007) . Journal of Cell Biology, 179(7), 1385-1398.
Bolderson E, Scorah J, Helleday T, Smythe C & Meuth M (2004) . Hum Mol Genet, 13(23), 2937-2945.
Jackson AP, Flett A, Smythe C, Hufton L, Wettey FR & Smythe E (2003) . J Cell Biol, 163(2), 231-236.
Sapkota GP, Deak M, Kieloch A, Morrice N, Goodarzi AA, Smythe C, Shiloh Y, Lees-Miller SP & Alessi DR (2002) . Biochemical Journal, 368(2), 507-516.
Way G, Morrice N, Smythe C & O'Sullivan AJ (2002) . MOLECULAR BIOLOGY OF THE CELL, 13(9), 3344-3354.
Feijoo C, Hall-Jackson C, Wu R, Jenkins D, Leitch J, Gilbert DM & Smythe C (2001) . JOURNAL OF CELL BIOLOGY, 154(5), 913-923.
Adams RR, Wheatleya SP, Gouldsworthy AM, Kandels-Lewis SE, Carmena M, Smythe C, Gerloff DL & Earnshaw WC (2000) . Current Biology, 10(17), 1075-1078.
Muller B, Link J & Smythe C (2000) . JOURNAL OF BIOLOGICAL CHEMISTRY, 275(32), 24284-24293.
Hall-Jackson CA, Cross DAE, Morrice N & Smythe C (1999) . ONCOGENE, 18(48), 6707-6713.
Hall-Jackson CA, Cross DAE, Jenkins DM & Smythe C (1999) . Biochemical Society Transactions, 27(3), A97-A97.
Drummond S, Ferrigno P, Lyon C, Murphy J, Goldberg M, Allen T, Smythe C & Hutchison CJ (1999) . JOURNAL OF CELL BIOLOGY, 144(2), 225-240.
Cross DAE & Smythe C (1998) . EXPERIMENTAL CELL RESEARCH, 241(1), 12-22.
Drummond S, Smythe C & Hutchison C (1997) 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.
Ball KL, Lain S, Fahraeus R, Smythe C & Lane DP (1997) . CURRENT BIOLOGY, 7(1), 71-80.
Jones C & Smythe C (1996) Activation of the Xenopus cyclin degradation machinery by full-length cyclin A. JOURNAL OF CELL SCIENCE, 109, 1071-1079.
King AG, Ozanne BW, Smythe C & Ashworth A (1995) Isolation and characterisation of a uniquely regulated threonine, tyrosine phosphatase (TYP 1) which inactivates ERK2 and p54(jnk). ONCOGENE, 11(12), 2553-2563.
LEWIS T, GROOM LA, SNEDDON AA, SMYTHE C & KEYSE SM (1995) 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.
HUTCHISON CJ, JENKINS HE, SMYTHE C & WHITFIELD WGF (1995) THE ROLE OF B-TYPE LAMINS IN THE ASSEMBLY OF A REPLICATION COMPETENT NUCLEUS. JOURNAL OF CELLULAR BIOCHEMISTRY, 123-123.
FERRIGNO P & SMYTHE C (1994) IDENTIFICATION OF NOVEL REGULATORY EVENTS IN NUCLEAR-ENVELOPE REASSEMBLY USING XENOPUS EGG EXTRACTS. JOURNAL OF CELLULAR BIOCHEMISTRY, 94-94.
LYON CE, HUTCHISON CJ, SMYTHE C, ALLEN TD & LANE EB (1994) MONOCLONAL-ANTIBODIES TO STRUCTURAL ELEMENTS OF AMPHIBIAN NUCLEAR ENVELOPES. JOURNAL OF CELLULAR BIOCHEMISTRY, 90-90.
ALESSI DR, SMYTHE C & KEYSE SM (1993) 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.
Kornbluth S, Smythe C & Newport JW (1992) . Molecular and Cellular Biology, 12(7), 3216-3223.
SMYTHE C & NEWPORT JW (1992) . CELL, 68(4), 787-797.
Smythe C & Newport JW (1991) , 449-468.
SMYTHE C & COHEN P (1991) . EUROPEAN JOURNAL OF BIOCHEMISTRY, 200(3), 625-631.
PFALLER R, SMYTHE C & NEWPORT JW (1991) . CELL, 65(2), 209-217.
HUBBARD MJ, DENT P, SMYTHE C & COHEN P (1990) . EUROPEAN JOURNAL OF BIOCHEMISTRY, 189(2), 243-249.
SMYTHE C, WATT P & COHEN P (1990) . EUROPEAN JOURNAL OF BIOCHEMISTRY, 189(1), 199-204.
SMYTHE C, VILLARPALASI C & COHEN P (1989) . EUROPEAN JOURNAL OF BIOCHEMISTRY, 183(1), 205-209.
PITCHER J, SMYTHE C & COHEN P (1988) . EUROPEAN JOURNAL OF BIOCHEMISTRY, 176(2), 391-395.
SMYTHE C, CAUDWELL FB, FERGUSON M & COHEN P (1988) . EMBO JOURNAL, 7(9), 2681-2686.
PITCHER J, SMYTHE C, CAMPBELL DG & COHEN P (1987) . EUROPEAN JOURNAL OF BIOCHEMISTRY, 169(3), 497-502.
Zhao A, Maple L, Jiang J, Myers KN, Jones CG, Gagg H, McGarrity-Cottrell C, Rominiyi O, Collis SJ, Wells G , Rahman M et al () . Cell Death & Disease, 15(12).
Rattajak P, Aroonkesorn A, Smythe C, Wititsuwannakul R & Pitakpornpreecha T () . Molecules, 29(9), 2113-2113.
Noakes FF, Smitten KL, Maple LEC, Bernardino de la Serna J, Robertson CC, Pritchard D, Fairbanks SD, Weinstein JA, Smythe CGW & Thomas JA () . Journal of the American Chemical Society.
Saeed HK, Jarman PJ, Sreedharan S, Mowll R, Auty AJ, Chauvet AAP, Smythe CGW, de la Serna JB & Thomas JA () . Chemistry – A European Journal.
Dröge F, Noakes FF, Archer SA, Sreedharan S, Raza A, Robertson CC, MacNeil S, Haycock JW, Carson H, Meijer AJHM , Smythe CGW et al () . Journal of the American Chemical Society.
Wragg A, Gill MR, Hill CJ, Su X, Meijer AJHM, Smythe C & Thomas JA () . Chem. Commun., 50(93), 14494-14497.
Dasso M, Smythe C, Milarski K, Kornbluth S & Newport JW () , 161-186.
Novodvorsky P, Watson O, Gray C, Wilkinson RN, Reeve S, Smythe C, Beniston R, Plant K, Maguire R, M. K. Rothman A , Elworthy S et al () . PLoS ONE, 10(10).

Chapters

Smythe C & Cohen P (1991) , EJB Reviews 1991 (pp. 149-155). Springer Berlin Heidelberg

Conference proceedings papers

Panomwan P & Smythe C (2015) Analysis of the Mechanism of DNA Damage and Replication Arrest-induced Histone mRNA DecayPornpen Panomwan*and Carl Smythe. FASEB JOURNAL, Vol. 29
Panomwan P & Smythe C (2014) Analysis of the mechanism of DNA damage and replication arrest-induced histone mRNA decay. FEBS JOURNAL, Vol. 281 (pp 65-65)
Gill MR, Thomas JA & Smythe C (2011) Ruthenium(II) polypyridyl complexes: In cellulo DNA binding and cytotoxicity. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 241
Mijiler B, Blackburn J, Feijoo C, Zhao X & Smythe C (2007) Are multiple checkpoint mediators involved in a checkpoint linking histone gene expression with DNA replication?. BIOCHEMICAL SOCIETY TRANSACTIONS, Vol. 35 (pp 1369-1371)
Beniston RG & Smythe CGW (2006) . BREAST CANCER RESEARCH, Vol. 8 (pp S5-S6)
Rzepecki R, Smythe C & Hutchison CJ (2002) The role of mitotic vesicles in the nuclear assembly. CELLULAR & MOLECULAR BIOLOGY LETTERS, Vol. 7(2) (pp 299-299)
Smythe C, Jenkins HE & Hutchison CJ (2000) . EMBO JOURNAL, Vol. 19(15) (pp 3918-3931)

Research group

Key collaborators

Prof Iain Coldham, Dept of Chemistry, University of ��«Ӱҵ
Dr James Thomas, Dept of Chemistry, University of ��«Ӱҵ
Dr Sarah Danson, Dept of Oncology, University of ��«Ӱҵ
Dr Ferdinando Di Cunto, Department of Genetics, Biology& Biochemistry, University of Torino.

Grants

Cystic Fibrosis Trust
Yorkshire Cancer Research
Royal Thai Higher Education Commission
Malaysia Trust Council (Majlis Amanah Rakyat)

Teaching activities

Undergraduate and postgraduate taught modules

Undergraduate:

BMS109-106 Pathobiology
BMS379 Cancer Biology (Co-ordinator)

Masters (MSc):

BMS6057 Cancer Biology (Co-ordinator)