Dr Judy Coulson

Introduction
Biography
Key Publications
Recent Publications
Contact Details

My lab is interested in understanding gene expression and signaling pathways germane to cancer.

I work closely with Sylvie Urbé, Ian Prior and Michael Clague, and together we run our labs as a collaborative environment that fosters joint research projects. This is escalating our interest in the role of reversible ubiquitination at the interface between signaling and transcription.

Work in my lab historically focused on two families of transcription factors, the transcriptional repressor REST/NRSF and bHLH factors including USF-2, which are aberrantly expressed in small cell lung cancer (SCLC). In addition to delineating their contribution to the expression of individual genes, we investigated the genome-wide REST-regulome in lung cancer. From this work we identified the SCG3 transcript as a biomarker of prognostic and predictive significance that can be used to detect circulating SCLC cells in peripheral blood (Moss et al, 2009). Most recently, Monica Faronato, a post-doc in my lab, has been screening for deubiquitinating enzymes (DUBs) that regulate REST stability and investigating how these may modulate REST function in lung cancer. One important contribution to the REST literature was our identification of an alternative REST splice variant in SCLC, which encodes an isoform lacking a key repression domain (Coulson et al, 2000). This interest in alternative isoforms was recently reignited by the DUBs (Thorne et al, 2011) and ras (a nascent collaboration with Ian Prior’s lab).

Intriguingly, some cancer-associated signaling pathways are also invoked by exercising or atrophying muscle. In particular the PI3K pathway, inhibition of which culminates in gene expression regulated by the FOXO family of transcription factors. Three current postgraduate students are focused on this pathway. Andrew Fisher (co-supervised with Jonathan Jarvis) is investigating FOXO-dependent transcription and the atrophy transcriptome in muscle. Joseph Sacco (a clinical fellow co-supervised with Michael Clague) is elucidating the role of DUBs in regulating the PI3K-FOXO axis in lung and other cancer cells. In 2010, the first basic science CRUK PhD studentship administered by the Liverpool Cancer Research UK Centre was jointly awarded to Mike Clague, Sylvie Urbé and myself; Yvonne Tang is screening for synthetic lethal interactions between DUBs and the PI3K pathway.

Research is funded by North West Cancer Research Fund, Clatterbridge Cancer Research, BBSRC, Cancer Research UK, and The Wellcome Trust.

Education
2003 PGcert L&T in HE, University of Liverpool
1994 PhD, University of London
1990 BSc, University of Salford

Appointments
2004 Senior Lecturer, Physiology, University of Liverpool
2001 Lecturer, Physiology & HACB, University of Liverpool
1999 Post-doctoral Fellow & PI, CRC unit, University of Nottingham
1995 Post-doctoral Associate, CRC unit, University of Nottingham
1994 Post-doctoral Associate, Pharmaceutical Sciences, Aston University

Honours and Awards
2003 British Association for Cancer Research / AstraZeneca Young Scientist of the Year

Moss AC, Jacobson GM, Walker LE, Blake NW, Marshall E, Coulson JM. (2009) SCG3 transcript in peripheral blood is a prognostic biomarker for REST deficient small cell lung cancer. Clin. Cancer Res. 15(1):274-283.

Coulson JM (2005) Transcriptional regulation: cancer, neurons and the REST. Current Biology 15(17): R665-8.

J. M. Coulson, J. L. Edgson, P. J. Woll, & J. P. Quinn. (2000) A splice variant of the NRSF repressor is expressed in small cell lung cancer: a potential role in de-repression of neuroendocrine genes and a useful clinical marker. Cancer Research 60 (7): 1840-1844.

S. I. Ahmed, J. Thompson, J. M. Coulson & P. J. Woll. (2000) Studies on the expression of endothelin, its receptor subtypes and converting enzymes in lung cancer and normal lung. Am. J. Respir. Cell Mol. Biol. 22: 422-431.

J. M. Coulson, C. E. Fiskerstrand, P. J. Woll & J. P. Quinn. (1999) Arginine vasopressin promoter regulation is mediated by a neuron restrictive silencer element in small cell lung cancer. Cancer Research 59 (20): 5128-5132.

J. M. Coulson, D. R. Poyner, A. Chantry, W. J. Irwin & S. Akhtar (1996) A non-antisense sequence-selective effect of a phosphorothioate oligodeoxynucleotide directed against the epidermal growth factor receptor in A431 Cells. Molecular Pharmacology 50(2): 314-325.

I. M. Khan & J. M. Coulson (1993) A novel method to stabilise antisense oligonucleotides against exonuclease degradation. Nucleic Acids Research 21(12): 2957-2958.

Thorne C, Eccles RL, Coulson JM, Urbe S, Clague M. (2011) Isoform specific localisation of the deubiquitinase USP33 to the Golgi Apparatus. Traffic (in press).

Faronato M, Urbé S, Coulson JM . (2010) USP15 (ubiquitin specific peptidase 15). Atlas Genet Cytogenet Oncol Haematol. http://AtlasGeneticsOncology.org/Genes/USP15ID44585ch12q14.html

Faronato M, Coulson JM. (2010) REST (RE1-silencing transcription factor). Atlas Genet Cytogenet Oncol Haematol. http://AtlasGeneticsOncology.org/Genes/RESTID44266ch4q12.html

Sacco JJ, Coulson JM, Clague MJ, Urbé S. (2010) Emerging roles of deubiquitinases in cancer-associated pathways. IUBMB Life 62(2):140-157.

Moss AC, Jacobson GM, Walker LE, Blake NW, Marshall E, Coulson JM. (2009) SCG3 transcript in peripheral blood is a prognostic biomarker for REST deficient small cell lung cancer. Clin. Cancer Res. 15(1):274-283.

Gao J, Coulson JM, Whitehouse A, Blake N. (2009) Reduction in RNA levels rather than retardation of translation is responsible for the inhibition of MHC class I antigen presentation by the glutamic Acid-rich repeat of HVS orf73. J. Virol. 83(1):273-82.

Clague MJ, Coulson JM & Urbé S (2008) Deciphering Histone H2A deubiquitination. Genome Research 9(1):202.
Moore LM, Fisher AG, Coulson JM, Salmons S, Jarvis JC. (2008) Real-time PCR to follow the transcriptional response of muscle to training. Artificial Organs 32(8):630-633.

Aladin F, Lautscham G, Humphries E, Coulson JM, Blake N. (2007) Targeting tumour cells with defects in the MHC Class I antigen processing pathway with CD8+ T cells specific for hydrophobic TAP- and Tapasin-independent peptides: the requirement for directed access into the ER. Cancer Immunol Immunother 56(8):1143-52.

Spencer EM, Chandler KE, Haddley K, Howard MR, Hughes D, Belyaev ND, Coulson JM, Stewart JP, Buckley NJ, Kipar A, Walker MC, Quinn JP (2006) Regulation and role of REST and REST4 variants in modulation of gene expression in in vivo and in vitro in epilepsy models. Neurobiol Disease 24(1): 41-52.

Morii H, Yamada T, Nakano I, Coulson JM, Mori N (2006) Site-specific phosphorylation of SCG10 in neuronal plasticity: role of Ser73 phosphorylation by N-methyl D-aspartic acid receptor activation in rat hippocampus. Neurosci Lett 396(3): 241-6.

Ocejo-Garcia M, Baokbah TAS, Ashurst HL, Cowlishaw D, Soomro I, Coulson JM & Woll PJ (2005) Roles for USF-2 in lung cancer proliferation and bronchial carcinogenesis. J Pathol 206: 151-159.

Coulson JM (2005) Transcriptional regulation: cancer, neurons and the REST. Current Biology 15(17): R665-8.

T. J. Viney, W. Gierasch, T. W. Schmidt, A. W. Sattar, R. E. Yaggie, J. P. Quinn, J. M. Coulson & A. F. Russo. (2004) Regulation of the Cell-Specific Calcitonin/CGRP Enhancer by USF and the Foxa2 Forkhead Protein. J Biol Chem. 279 49948-49955.

S. Khan, J. M. Coulson & P. J. Woll. (2004) Genetic abnormalities in plasma DNA of patients with lung cancer and other respiratory diseases. Int J Cancer 110(6):891-5.

D. K. Petkova, C. Clelland, J. Ronan, L. Pang, J. M. Coulson, S. Lewis & A. J. Knox. (2004) Overexpression of cyclooxygenase-2 in non-small cell lung cancer. Resp Med 98(2): 164-172.

J. M. Coulson, J. L. Edgson, Z. V. Marshall-Jones, R. J. Mulgrew, J. P. Quinn & P. J. Woll. (2003) Upstream Stimulatory Factor Activates the Vasopressin Promoter via Multiple Motifs, Including a Non-canonical E-box. Biochem J 369(3): 549-561.

M. T. Ghorbel, J. M. Coulson & D. Murphy. (2003) Cross talk between hypoxic and circadian pathways: co-operative roles for hypoxia-inducible factor-1 alpha and CLOCK in transcriptional activation of the vasopressin gene. Mol Cell Neurosci 22(3): 396-404.

J. M. Coulson, M. Ocejo-Garcia & P.J. Woll. (2003) The Neuroendocrine Phenotype of Small Cell Lung Cancer. Methods Mol Med. 74: 61-73.

J. M. Coulson, S.I. Ahmed, J.P. Quinn & P.J. Woll. (2003) Detection of small cell lung cancer by RT-PCR for neuropeptides, neuropeptide receptors, or a splice variant of the neuron restrictive silencer factor. Methods Mol Med. 75: 335-52.

J. M. Coulson. (2002) Positive and negative regulators of the vasopressin gene promoter in small cell lung cancer. Prog Brain Res. 139: 329-43.

J. P. Quinn, Z. V. Marshall-Jones , V. J. Bubb & J. M. Coulson. (2002) Neuron restrictive silencer factor as a modulator of neuropeptide gene expression. Regulatory Peptides 108 (2-3): 135-141.

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