Trosolwg
Research overview
My main lines of research are:
- To exploit the use of transgenic mouse models to determine the critical molecular events which contribute to the initiation and progression of tumourigenesis (primarily within the intestine and liver)
- To investigate the importance of the genes Cbx3 and HMGB1 in intestinal homeostasis and tumourigenesis
- To determine the epigenetic consequences of altered gestational diet, and ascertain the significance of these on lifetime tumour risk
- To investigate the alternative roles of APC (Adenomatous polyposis coli) which contribute to tumourigenesis but are independent to APC's role regulating Wnt signalling
Bywgraffiad
I have worked as a postdoctoral research associate within the group of Prof. Alan Clarke in Cardiff school of Biosciences since Oct 2002. My research utilises a number of clinically relevant, transgenic mouse models of cancer (principally intestinal and liver cancer) with the aim of clarifying or establishing some of the critical molecular events that contribute to the initiation, establishment and progression of cancer.
Prior to moving to Cardiff, I worked within the group of Prof Wolf Reik at the Babraham Institute, Cambridge, under whose supervision I also completed a PhD (awarded in Sept 2000). Here my research focused on understanding the epigenetic regulation of the imprinted locus on mouse distal chromosome 7 (a chromosome region involved in foetal overgrowth and cancer susceptibility) and I characterised the molecular basis of, and consequential imprinted phenotype of, the novel radiation-induced mouse mutation Minute (Mnt).
Preceding this I graduated from the University of Bath with a BSc honours degree in Applied Biology in 1996. During my degree course I completed a year's research in The Institute of Medical Genetics, Cardiff, where I characterised the inheritance of multiple genetic markers within families of Rett syndrome patients (a childhood neurodevelopmental disorder) and refined the genetic map of this disease.
My objective now is to develop my own research group using the expertise I have obtained from working at Cambridge and Cardiff.
Ymrwymiadau siarad cyhoeddus
- 6th Mammalian Genetics, Development and Disease Meeting, University of Bath, Friday 6th July 2012
- "Hunk/Mak-v is a negative regulator of intestinal cell proliferation"
- NCRI (national cancer research Institute) cancer conference 6-9 Nov 2011, BT Convention Centre, Liverpool, UK
- "The impact of APC2 on somatic stem cells and tumourigenesis"
- Karen Reed, Carl Daly, Paul Shaw, Alan Clarke
- Warwick 2008 Genes and Cancer Meeting, December 8-10, 2008
- "Beta-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of Apc loss in the liver"
- Karen R Reed*, Dimitris Athineos*, Valerie S Meniel*, Julie A Wilkins, Rachel A Ridgway, Zoé D. Burke, Vanesa Muncan, Alan R Clarke, Owen J Sansom
- NCRI (national cancer research Institute) cancer conference 8-11Oct 2006, The ICC, Birmingham, UK
- A BACR/Gordon Hamilton-fairly young investigator award "P53 status does not affect the early phenotype seen following the conditional loss of APC."
- Reed KR, Sansom OJ, Meniel V, Marsh V, Clarke AR
- Warwick 2004 Genes and Cancer Meeting, December 13-15, 2004
- "PPARd deficiency does not modify APC mediated tumourigenesis"
- Karen R. Reed, Anthony J. Hayes, Owen J. Sansom, Hannah Brinkman, Jeffrey Peters, Alan R. Clarke
- Imprinting and growth congress 2002. 11-13 April 2002, London
- "The Minute mutation and a comparative genomics approach for the isolation of enhancers controlling Igf2 expression."
- Davies K, Smith P, dean, W, Bowden L, Sasaki H, Cattanach B, Reik W.
- The International Genomic Imprinting Meeting 24-26 Aug 1999, Dublin
- ORAL Presentation: "The radiation-induced mouse mutation minute (Mnt) affects the mesoderm enhancer for IGF2 and methylation of H19."
- Davies K, Bowden L, Rasberry C, Cattanach B, Reik W.
Cyhoeddiadau
2020
- Queiroz, C. J. et al. 2020. NAP1L1: a novel human colorectal cancer biomarker derived from animal models of Apc inactivation. Frontiers in Oncology 10, article number: 1565. (10.3389/fonc.2020.01565)
2019
- Mohamed, N., Hay, T., Reed, K. R., Smalley, M. J. and Clarke, A. R. 2019. APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression. BMC Cancer 19, article number: 677. (10.1186/s12885-019-5867-y)
2018
- Young, M., Daly, C., Taylor, E., James, R., Clarke, A. and Reed, K. 2018. Subtle deregulation of the Wnt-signalling pathway through loss of Apc2 reduces the fitness of intestinal stem cells. Stem Cells 36(1), pp. 114-122. (10.1002/stem.2712)
- Burke, Z. D., Reed, K. R., Yeh, S., Meniel, V. S., Sansom, O. J., Clarke, A. R. and Tosh, D. 2018. Spatiotemporal regulation of liver development by the Wnt/β- catenin pathway. Scientific Reports 8, article number: 2735. (10.1038/s41598-018-20888-y)
- Burke, Z. D., Reed, K. R., Yeh, S., Meniel, V., Sansom, O. J., Clarke, A. R. and Tosh, D. 2018. Spatiotemporal regulation of liver development by the Wnt/β-catenin pathway. Scientific Reports 8(1) (10.1038/s41598-018-20888-y)
2017
- Daly, C. S. et al. 2017. Functional redundancy between Apc and Apc2 regulates tissue homeostasis and prevents tumorigenesis in murine mammary epithelium. Oncogene 36(13) (10.1038/onc.2016.342)
2016
- Young, M. and Reed, K. R. 2016. Organoids as a model for colorectal cancer. Current Colorectal Cancer Reports 12(5), pp. 281-287. (10.1007/s11888-016-0335-4)
- Reed, K. R. et al. 2016. Secreted HMGB1 from Wnt activated intestinal cells is required to maintain a crypt progenitor phenotype. Oncotarget 7(32), pp. 51665-51673. (10.18632/oncotarget.10076)
2015
- Huels, D. J. et al. 2015. E-cadherin can limit the transforming properties of activating β‐catenin mutations. EMBO Journal 34(18), pp. 2321-2333. (10.15252/embj.201591739)
- Reed, K. R. et al. 2015. Correction for Reed et al., B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver. Proceedings of the National Academy of Sciences of the United States of America 112(10), pp. E1168. (10.1073/pnas.1502294112)
- Reed, K. R. et al. 2015. Hunk/Mak-v is a negative regulator of intestinal cell proliferation. BMC Cancer 15, article number: 110. (10.1186/s12885-015-1087-2)
2013
- Hammoudi, A. et al. 2013. Proteomic profiling of a mouse model of acute intestinal Apc deletion leads to identification of potential novel biomarkers of human colorectal cancer (CRC). Biochemical and Biophysical Research Communications 440(3), pp. 364-370. (10.1016/j.bbrc.2013.08.076)
2012
- Feng, G. J. et al. 2012. Conditional disruption of Axin1 leads to development of liver tumors in mice. Gastroenterology 143(6), pp. 1650-1659. (10.1053/j.gastro.2012.08.047)
- Reed, K. R., Tunster, S. J., Young, M., Carrico, A. S., John, R. M. and Clarke, A. R. 2012. Entopic overexpression of Ascl2 does not accelerate tumourigenesis in ApcMin mice. Gut 61(10), pp. 1435-1438. (10.1136/gutjnl-2011-300842)
2011
- Kant, P. et al. 2011. Rectal epithelial cell mitosis and expression of macrophage migration inhibitory factor are increased 3 years after Roux-en-Y gastric bypass (RYGB) for morbid obesity: implications for long-term neoplastic risk following RYGB. Gut 60(7), pp. 893-901. (10.1136/gut.2010.230755)
2010
- Cole, A. M. et al. 2010. Cyclin D2-cyclin-dependent kinase 4/6 is required for efficient proliferation and tumorigenesis following Apc loss. Cancer Research 70(20), pp. 8149-8158. (10.1158/0008-5472.CAN-10-0315)
2009
- Burke, Z. D., Reed, K. R., Phesse, T., Sansom, O. J., Clarke, A. R. and Tosh, D. 2009. Liver zonation occurs through a β-catenin–dependent, c-Myc–independent mechanism. Gastroenterology 136(7), pp. 2316-2324. (10.1053/j.gastro.2009.02.063)
2008
- Reed, K. R. et al. 2008. B-catenin deficiency, but not Myc deletion, suppresses the immediate phenotypes of APC loss in the liver. Proceedings of the National Academy of Sciences of the United States of America 105(48), pp. 18919-18923. (10.1073/pnas.0805778105)
- Reed, K. R., Meniel, V., Marsh Durban, V., Cole, A., Sansom, O. J. and Clarke, A. R. 2008. A limited role for p53 in modulating the immediate phenotype of Apc loss in the intestine. BMC Cancer 8, article number: 162. (10.1186/1471-2407-8-162)
- Phesse, T., Parry, L., Reed, K. R., Ewan, K. B. R., Dale, T. C., Sansom, O. J. and Clarke, A. R. 2008. Deficiency of Mbd2 attenuates Wnt induced tumourigenesis via deregulation of a novel Wnt inhibitor, Lect.2. Molecular and Cellular Biology 28(19), pp. 6094-6103. (10.1128/MCB.00539-08)
2007
- Sansom, O. J. et al. 2007. Myc deletion rescues Apc deficiency in the small intestine. Nature 446(7136), pp. 676-679. (10.1038/nature05674)
2006
- Reed, K. R., Sansom, O. J., Hayes, A. J., Gescher, A. J., Peters, J. M. and Clarke, A. R. 2006. PPARδ status and mismatch repair mediated neoplasia in the mouse intestine. BMC Cancer 6(113) (10.1186/1471-2407-6-113)
2005
- Sansom, O. J., Griffiths, D. F. R., Reed, K. R., Winton, D. J. and Clarke, A. R. 2005. Apc deficiency predisposes to renal carcinoma in the mouse. Oncogene 24, pp. 8205-8210. (10.1038/sj.onc.1208956)
- Sansom, O. J., Reed, K. R., van de Wetering, M., Muncan, V., Winton, D. J., Clevers, H. and Clarke, A. R. 2005. Cyclin D1 is not an immediate target of β-Catenin following Apc loss in the intestine. Journal of Biological Chemistry 280(31), pp. 28463-28467. (10.1074/jbc.M500191200)
2004
- Sansom, O. J. et al. 2004. Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes and Development 18(12), pp. 1385-1390. (10.1101/gad.287404)
- Reed, K. R., Sansom, O. J., Hayes, A. J., Gescher, A. J., Winton, D. J., Peters, J. M. and Clarke, A. R. 2004. PPARδ status and Apc-mediated tumourigenesis in the mouse intestine. Oncogene 23(55), pp. 8992-8996. (10.1038/sj.onc.1208143)
Addysgu
Student supervision
- Charmmy Ka Ian Lio 1st year PhD student - Tenovus Funded
- Madeleine Young 2st year PhD student
- Carl Daly PhD student
- I mentored Dr Paul Shaw during his PhD (graduated 2010)
I have organised and supervised projects for the summer students:
- Ben Hopkins (voluntary) 2012
- Adam Lynch (voluntary) 2011
- James Lamb (Nuffield Foundation Bursary A level student) 2011
- James Moggridge (Nuffield Foundation Bursary A level student) 2011
- Ben Hopkins (Nuffield Foundation Bursary A level student) 2010
- James Platt (Nuffield Foundation Undergraduate Bursary student) 2008
I have organised and supervised projects for the following final year undergraduate students:
- Rhys Donovan, Rezwana Chowdhury and Swawiza Gohobur 2012 (Engagement project students)
- Natalie Izod 2012 (lab project - co-supervised with Miss M Young)
- Scott Hart 2011
- Nesibe-princess Gemici 2010
- Adam Carrico 2009
- Gokcen Ilktac 2008
- David Hunt 2007
- Ryan Russell 2006
- Bethan Medina 2005
Mouse models of human diseases facilitate an understanding of the mechanisms that contribute to the initiation, establishment and progression of diseases such as cancer in human.
I am interested in transcriptional regulation and my research aim is to identify genes and pathways that are critical in the initiation and progression of cancer. To date, my research has utilised multiple clinically relevant, transgenic mouse models of intestinal cancer, to a) understand the transcriptional changes that occur following the loss of the tumour suppressor gene APC and b) investigate the importance of some of these changes in the aetiology of intestinal cancer. I have begun to develop my own research programme looking to identify clinically relevant biomarkers and drug targets for colorectal cancer, and examining the importance of candidate genes (Cbx3 and Hmgb1) in intestinal homeostasis and neoplasia.
The (APC) tumour suppressor protein is well characterised as a key regulator of Wnt signalling, and elevation of the levels of b-catenin is a known consequence of loss of APC function. Mutations in the APC gene are associated with both familial and sporadic colon cancer pathogenesis and links with other cancers including hepatocellular carcinoma and renal cancer are reported.
The conditional deletion of Apc in the adult intestine or liver quickly results in the neoplasm. Transcriptome analysis using affymetrix microarrays has identified a number of transcripts that are differentially regulated following the conditional loss of Apc in this system and the data generated has been used to establish some of the critical molecular events that contribute to the initiation and progression of tumourigenesis (e.g. Sansom et al 2004+2007, Reed et al 2004, 2006+2008).
Outreach activities
The list of my outreach activities, including some blogs about my experiences can be found on my STEMnet pages : http://networking.stemnet.org.uk/users/100224
My first involvement in public engagement was through the Beacons for Wales Researchers in Residence scheme, but I have since participated in several activities; Some (e.g, the Beacons for Wales $1000 genome project in Park Prison, Bridgend or the "Learn about Life" events in Cardiff School of Biosciences) have been pre-organised by others, while other activities I have initiated and organised myself (e.g. school visits to Goytre Fawr Primary school and Archdeacon John Lewis Primary school). I have developed a highly successful interactive activity demonstrating how the polymerase chain reaction works which I have run as a 3 hour workshop for visiting pre-GCSE pupils who were participating in a Hands-On Science Summer Residential course.
Awards and funding obtained
- CUROP summer studentship 2013
- Cardiff University Community Engagement Small Award 2012
- Tenovus PhD studentship to support Charmmy Ka Ian Lio 2011
- The Biochemical Society Scientific Outreach Grant, 2011
- The Nuffield Foundation Science Bursary, 2011
- The Royal Society Partnership grant, 2010
- The Nuffield Foundation Science Bursary, 2010
- The Nuffield Foundation Undergraduate Research Bursary, 2008
- BACR meeting bursary, 2008
- BACR Hamilton-Fairley Young Investigator Award, 2006
Collaborators
- Dr Owen Sansom, Cancer Research UK Beatson Laboratories, Glasgow
- Dr David Tosh and Dr Zoe Burke, Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath
- Dr John Jenkins, Gastroenterology Research Unit, The University of Liverpool
- Dr David Bell, School of Biology, University of Nottingham
- Dr Ros John, Cardiff School of Biosciences
- Dr Vladimir Buchman, Cardiff School of Biosciences
