Paul Shore is working on the regulation of gene expression in metastatic breast cancer. Our goal is to prevent metastatic breast cancer by understanding the molecular basis for the development of specific metastatic phenotypes. Work focuses on the molecular mechanisms that determine changes in gene expression, which subsequently enable disseminated breast cancer cells to colonise specific tissues.

Senior Lecturer

The University of Manchester
Michael Smith Building
Oxford Road
Manchester
M13 9PT

Tel: +44 (0)161 275 5978
Email: paul.shore@manchester.ac.uk
Web: http://paulshorelab.org

1985 - 1993 BSc and PhD, Biochemistry, University of Sheffield, UK

1993 - 1996 Postdoc, University of Newcastle, UK

1996 - Short Term EMBO Fellowship, Max-Planck Institute, Freiburg, Germany

1996 - 1999 Wellcome Trust International Prize Research Fellowship, WEHI, Australia

2000 - 2004 Wellcome Trust Career Development Fellowship, University of Manchester

2004 - 2009 Lecturer/Senior Lecturer, University of Manchester

Cytoskeletal Filamin A Differentially Modulates RNA Polymerase III Gene Transcription in Transformed Cell Lines.

Wang J, Zhao S, Wei Y, Zhou Y, Shore P, Deng W.

J Biol Chem. 2016. 291(48):25239-25246.

Runx2 is a novel regulator of mammary epithelial cell fate in development and breast cancer.

Owens TW, Rogers RL, Best S, Ledger A, Mooney AM, Ferguson A, Shore P, Swarbrick A, Ormandy CJ, Simpson PT, Carroll JS, Visvader JE, Naylor MJ.

Cancer Res. 2014 Jul 23. pii: canres.0053.2014.

Repression of Transcription by WT1-BASP1 Requires the Myristoylation of BASP1 and the PIP2-Dependent Recruitment of Histone Deacetylase.

Toska E, Campbell HA, Shandilya J, Goodfellow SJ, Shore P, Medler KF, Roberts SG. (In-press).

Cell Reports, 2(3), 462.

Cytoskeletal protein filamin A is a nucleolar protein that suppresses ribosomal RNA gene transcription.

Wensheng Deng, Cesar Lopez-Camacho, Jen-Yang Tang, Daniel Mendoza-Villanueva, Apolinar Maya-Mendoza, Dean A. Jackson, and Paul Shore. (2012).

Proceedings of the National Academy of Sciences of the United States of America, 109(5), 1524. eScholarID:153106 | DOI:10.1073/pnas.1107879109

Metastatic breast cancer cells inhibit osteoblast differentiation through the Runx2/CBFß-dependent expression of the Wnt antagonist, sclerostin.

Mendoza-Villanueva, D., Zeef, L. & Shore, P (2011).

Breast cancer research : BCR, 13(5), R106. eScholarID:134983 | PMID:22032690 | DOI:10.1186/bcr3048

Inhibition of Notch1 signaling by Runx2 during osteoblast differentiation.

Ann, E., Kim, H., Choi, Y., Kim, M., Mo, J., Jung, J., Yoon, J., Kim, S., Moon, J., Seo, M., Hong, J., Jang, W., Shore, P., Komori, T., Koh, J. & Park, H (2011).

J Bone Miner Res, 26(2), 317-30. eScholarID:117090 | PMID:20740684 | DOI:10.1002/jbmr.227

The Runx transcriptional co-activator, CBFbeta, is essential for invasion of breast cancer cells.

Mendoza-Villanueva D, Deng W, Lopez-Camacho C, Shore P. (2010).

Molecular Cancer, 9(171), eScholarID:117083 | DOI:10.1186/1476-4598-9-171

Our goal is to prevent metastatic breast cancer by understanding the molecular basis for the development of specific metastatic phenotypes. Our work focuses on the molecular mechanisms that determine changes in gene expression, which subsequently enable disseminated breast cancer cells to colonise specific tissues. Breast cancers frequently metastasise to the skeleton where they cause osteolytic bone destruction. Effective treatment of bone metastasis remains a considerable clinical challenge. In the UK 12,000 patients that die from breast cancer annually have bone metastasis. How breast cancer spreads so readily to the skeleton is not fully understood, and there are currently no treatments that specifically prevent breast cancers from spreading to bone. There is therefore an urgent need to identify the key molecules involved in breast cancer bone metastasis in order to develop successful therapies for these patients.

Breast cancers preferentially spread to bone. Bone metastases cause extreme bone pain, fractures, nerve compression, and hypercalcaemia; the average survival time for patients is approximately two years. The development of therapies to combat bone metastasis largely depends on identifying new molecular targets for pharmacological intervention. What causes breast and prostate cancer cells to preferentially colonise the bone is largely unknown. However, work in my laboratory on the transcription factor Runx2 has revealed a fundamental molecular link between breast and bone-specific gene expression. Evidence is now accumulating that Runx2 controls metastatic cell invasion and contributes to tumour growth and osteolytic disease. Our ongoing research is focussed on identifying Runx2-regulated genes in metastatic cancer cells that contribute to invasion and early colonization phases of the bone microenvironment.

For further information see our lab website: http://paulshorelab.org

Missense mutations that cause Van der Woude syndrome and popliteal pterygium syndrome affect the DNA-binding and transcriptional activation functions of IRF6.

Little HJ, Rorick NK, Su LI, Baldock C, Malhotra S, Jowitt T, Gakhar L, Subramanian R, Schutte BC, Dixon MJ, Shore P. (2009).

Human Molecular Genetics, 18(3), 535-545. eScholarID:1c8078 | DOI:10.1093/hmg/ddn381

Irf6 is a key determinant of the keratinocyte proliferation-differentiation switch.

Richardson RJ, Dixon J, Malhotra S, Hardman MJ, Knowles L, Boot-Handford RP, Shore P, Whitmarsh A, Dixon MJ. (2006).

Nature Genetics, 38(11), 1329-1334. eScholarID:68278 | DOI:10.1038/ng1894

A role for Runx2 in normal mammary gland and breast cancer bone metastasis.

Shore P. (2005).

Journal of cellular biochemistry, 96(3), 484-9. eScholarID:1c5347 | PMID:16052475 | DOI:10.1002/jcb.20557

Oct-1 counteracts autoinhibition of Runx2 DNA binding to form a novel Runx2/Oct-1 complex on the promoter of the mammary gland-specific gene beta-casein.

Inman CK, Li N, Shore P. (2005).

Molecular and cellular biology, 25(8), 3182-93. eScholarID:1c5346 | PMID:15798204 | DOI:10.1128/MCB.25.8.3182-3193.2005

The osteoblast transcription factor Runx2 is expressed in mammary epithelial cells and mediates osteopontin expression.

Inman CK, Shore P. (2003).

J Biol Chem, 278(49), 48684-9. eScholarID:1c1912 | PMID:14506237 | DOI:10.1074/jbc.M308001200

Transcriptional regulation of the human MIP-1alpha promoter by RUNX1 and MOZ.

Bristow CA, Shore P. (2003).

Nucleic acids research, 31(11), 2735-44. eScholarID:1c1913 | PMID:12771199 | DOI:10.1093/nar/gkg401

Oct-2 regulates CD36 gene expression via a consensus octamer, which excludes the co-activator OBF-1.

Shore P, Dietrich W, Corcoran LM. (2002).

Nucleic acids research, 30(8), 1767-73. eScholarID:1c1914 | PMID:11937630 | DOI:10.1093/nar/30.8.1767

Gene structure alternative splicing, and chromosomal localization of pro-apoptotic Bcl-2 relative Bim.

Bouillet P, Zhang LC, Huang DC, Webb GC, Bottema CD, Shore P, Eyre HJ, Sutherland GR, Adams JM. (2001).

Mammalian genome : official journal of the International Mammalian Genome Society, 12(2), 163-8. eScholarID:1c3435 | PMID:11210187 | DOI:10.1007/s003350010242

Shore P. and Sharrocks A.D. (2000). Regulation of Transcription by Extracellular Signals. In J. Locker (Ed.), Transcription Factors. (pp. 10). Bios Scientific Ltd. eScholarID:3c250

Transcription Factors in B-Cell Development and Function.

Corcoran, LM and SHORE P. (2000).

The Immunologist, 8, 11-13. eScholarID:1c6589

The mechanism of phosphorylation-inducible activation of the ETS-domain transcription factor Elk-1.

Yang SH, Shore P, Willingham N, Lakey JH, Sharrocks AD. (1999).

The EMBO journal, 18(20), 5666-74. eScholarID:1c3436 | PMID:10523309 | DOI:10.1093/emboj/18.20.5666

DNA binding by MADS-box transcription factors: a molecular mechanism for differential DNA bending.

West AG, Shore P, Sharrocks AD. (1997).

Molecular and cellular biology, 17(5), 2876-87. eScholarID:1c3437 | PMID:9111360

Determinants of DNA-binding specificity of ETS-domain transcription factors.

Shore P, Whitmarsh AJ, Bhaskaran R, Davis RJ, Waltho JP, Sharrocks AD. (1996).

Molecular and cellular biology, 16(7), 3338-49. eScholarID:1c3438 | PMID:8668149

The ETS-domain transcription factors Elk-1 and SAP-1 exhibit differential DNA binding specificities.

Shore P, Sharrocks AD. (1995).

Nucleic acids research, 23(22), 4698-706. eScholarID:1c3439 | PMID:8524663 | DOI:10.1093/nar/23.22.4698

Integration of MAP kinase signal transduction pathways at the serum response element.

Whitmarsh AJ, Shore P, Sharrocks AD, Davis RJ. (1995).

Science, 269(5222), 403-7. eScholarID:1c3440 | PMID:7618106 | DOI:10.1126/science.7618106

DNA bending in the ternary nucleoprotein complex at the c-fos promoter.

Sharrocks AD, Shore P. (1995).

Nucleic acids research, 23(13), 2442-9. eScholarID:1c3441 | PMID:7630721 | DOI:10.1093/nar/23.13.2442

The MADS-box family of transcription factors.

Shore P, Sharrocks AD. (1995).

European journal of biochemistry / FEBS, 229(1), 1-13.

Characterization of the Elk-1 ETS DNA-binding domain.

Shore P, Bisset L, Lakey J, Waltho JP, Virden R, Sharrocks AD. (1995).

Journal of Biological Chemistry, 270(11), 5805-11. eScholarID:1c3443 | PMID:7890710

The transcription factors Elk-1 and serum response factor interact by direct protein-protein contacts mediated by a short region of Elk-1.

Shore P, Sharrocks AD. (1994).

Molecular and cellular biology, 14(5), 3283-91. eScholarID:1c3444 | PMID:8164681

The DNA recognition subunit of a DNA methyltransferase is predominantly a molten globule in the absence of DNA.

Hornby DP, Whitmarsh A, Pinarbasi H, Kelly SM, Price NC, Shore P, Baldwin GS, Waltho J. (1994).

FEBS letters, 355(1), 57-60. eScholarID:1c5753 | PMID:7957963 | DOI:10.1016/0014-5793(94)01171-0