I have worked on research projects characterising DNA variants in cancers and I now run a research group focused on identifying functional and regulatory DNA and RNA variants that may affect risk of breast cancer and other cancers with putative shared aetiology. We collaborate with Dr Francesco Crea's group within the Open University, identifying long non-coding RNAs (lncRNA) variants putatively underlying risk of prostate and other cancers. I also collaborate with Professor Angela Cox (University of Sheffield) on the Identification of regulatory DNA variants in apoptosis genes associated with breast cancer risk (Yorkshire Cancer Research) and Professor Nicola J Camp (University of Utah, USA). My first post-doctoral position was in Professor Angela Cox's group where we were the first to identify that the Caspase 8 gene (Casp8) was associated with risk of breast cancer and subsequently identify CASP8 and other apoptosis DNA variants (Yorkshire Cancer Research, Cancer Research UK, Breast Cancer Campaign, and the Wellcome Trust). Whilst doing my PhD (The role of p14ARF in familial and sporadic melanoma, funded by Imperial Cancer Research now called Cancer Research UK) in Professor D Timothy Bishop and Professor Julia Newton-Bishops's group with Professor Margaret A Knowles (University of Leeds) I was the first to: comprehensively screen for deletions on chromosome 9p in melanoma families and in sporadic melanomas (at a time when it was difficult for detect deletions and loss of heterozygosity, LOH); to identify p14ARF [CDKN2A-ARF gene (exon 1β)] as a tumour suppressor gene; identify the MTAP to KIAA1 gene region as important in melanoma aetiology and a candidate locus for the location of a tumour suppressor gene; and contributed to being the first to identify that introns are important in disease with the detection of a splicing variant (IVS2-105) in melanoma families.
Tools: genetic (e.g. high throughput PCR, allelic discrimination, sequencing, MLPA, qPCR), molecular (e.g. cell culture, flow cytometry), and data mining using publically available online databases e.g. dbSNP, Ensembl, UCSC, GEO etc. Mainly gene expression tools.
Key words: cancer, breast cancer, genetics, molecular science, epidemiology, bioinformatics, data mining, DNA variants, RNA variants, DNA characterisation, RNA expression, protein expression.
The European Association for Cancer Research (EACR), Nottingham, UK (from 2018)
The British Association for Cancer Research (BACR), Leeds, UK (from 2018)
The Genetics Society, London, UK (from 2017)
Participated with the Breast Cancer Association Consortium (BCAC, UK), North of England Genetic Epidemiology Group (NEGEG, UK), and the Melanoma Genetics Consortium (GenoMEL, UK)
Two research poster prizes 2009, Yorkshire Cancer Research Annual Science Meeting (Harrogate)
Research Team of the Year 2008, Awarded by Baroness Fookes of Plymouth DBE DL, patron of the Breast Cancer Campaign (House of Lords)
Sarah Jane Cross memorial prize, University of Wales, Aberystwyth 1997
Academic excellence letter, Biological Sciences, University of Wales, Aberystwyth 1997
Pucci, P., Venalainen, E., Alborelli, I., Quagliata, L., Mather, R., Rigas, S., Romero, I., Wang, Y., Crea, F. (2019). HORAS5 promotes cabazitaxel resistance in castration resistant prostate cancer via a BCL2A1-dependent survival mechanism. Annals of Oncology, 30(5)
Silvestri, R., Pucci, P., Venalainen, E., Matheou, C., Mather, R., Chandler, S., Aceto, R., Rigas, S., Wang, Y., Rietdorf, K., Bootman, M., Crea, F. (2019). T-type calcium channels drive the proliferation of androgen-receptor negative prostate cancer cells. The Prostate, 79(13) pp. 1580–1586
Paolicchi, E., Fornaro. L., Landi. S., Rigas. S., Crea. F., (2017). EZH2 Single Nucleotide Variants (SNVs): Diagnostic and Prognostic Role in 10 Solid Tumor Types. Epigenomes, 1(3): 18
Camp, N. J., Lin, W-Y., Bigelow, A., Burghel, G., Mosbruger, T., Parry, M., Waller, R., Rigas, S., Tai, P-Y., Berrett, K-C., Rajamanickam, V., Cosby, R., Brock, I., Jones, B., Connley, D., Sargent, R., Wang, G., Factor, R., Bernard, P., Cannon-Albright, L-A., Knight, S., Abo, R., Werner, T., Reed, M. WR., Gertz, J., Cox, A., (2016) Discordant Haplotype Sequencing Identifies Functional Variants at the 2q33 Breast Cancer Risk Locus. Cancer Research 76(7):1916-25
Camp NJ, Parry M, Knight S, Abo R, Elliott G, Rigas SH, Balasubramanian SP, Reed MWR, McBurney H, Latif A, Newman WG, Cannon-Albright LA, Evans DG, Cox A (2012) Fine-Mapping CASP8 Risk Variants in Breast Cancer. Cancer Epidemiology Biomarkers & Prevention 21: 176-181
Shephard ND, Abo R, Rigas SH, Frank B, Lin WY, Brock IW, Shippen A, Balasubramanian SP, Reed MWR, Bartram CR, Meindl A, Schmutzler RK, Engel C, Burwinkel B, Cannon-Albright LA, Allen-Brady K, Camp NJ, Cox A (2009) A Breast Cancer Risk Haplotype in the Caspase-8 Gene. Cancer Research 69: 2724-2728
Freedberg DE, Rigas SH, Russak J, Gai W, Kaplow M, Osman I, Turner F, Randerson-Moor JA, Houghton A, Busam K, Bishop DT, Bastian BC, Newton-Bishop JA, Polsky D (2008) Frequent p16-independent inactivation of p14(ARF) in human melanoma. Journal of the National Cancer Institute 100: 784-795
Frank B, Rigas SH, Bermejo JL, Wiestler M, Wagner K, Hemminki K, Reed MW, Sutter C, Wappenschmidt B, Balasubramanian SP, Meindl A, Kiechle M, Bugert P, Schmutzler RK, Bartram CR, Justenhoven C, Ko YD, Bruning T, Brauch H, Hamann U, Pharoah PPD, Dunning AM, Pooley KA, Easton DF, Cox A, Burwinkel B (2008) The CASP8-652 6N del promoter polymorphism and breast cancer risk: a multicenter study. Breast Cancer Research and Treatment 111: 139-144
Mistry SH, Taylor C, Randerson-Moor JA, Harland M, Turner F, Barrett JH, Whitaker L, Jenkins RB, Knowles MA, Bishop JAN, Bishop DT (2005) Prevalence of 9p21 deletions in UK melanoma families. Genes Chromosomes & Cancer 44: 292-300
Harland M, Mistry S, Bishop DT, Bishop JAN (2001) A deep intronic mutation in CDKN2A is associated with disease in a subset of melanoma pedigrees. Human Molecular Genetics 10: 2679-2686
PGC HEP, Postgraduate Certificate in Higher Education Practice, University of Bradford, 2016
PhD. School of Medicine, University of Leeds (Leeds Institute of Cancer and Pathology, Section of Epidemiology and Biostatisics), St James' Hospital, 2004
The role of p14ARF in familial and sporadic melanoma
BSc. (HONS) 1st, Genetics, Aberystwyth University, Wales, 2000
Familial hypercholesterolaemia, causitive role in atherosclerosis, other risk factors, and treatment
Stephen Chandler (PhD student)
Perla Pucci (PhD student)
Priyadarsini Nambiar (research fellow)
PhD student: Stephen Chandler
Title: Identification of functional variants in breast and other cancers with putative shared aetiology.
Funding: The Open University
The role or function of DNA and RNA variants associated with cancers, as identified in genome wide association studies (GWAS) and candidate gene approaches, are largely unknown. There is evidence that they may be involved in the regulation of gene expression e.g. as expression quantitative trait locus (eQTL) or splicing quantitative trait locus (sQTL) variants, or involved in certain cellular pathways such as: apoptosis, signal transduction, angiogenesis, cell motility, communication and development, DNA repair and replication, metabolism, and endocrine or nervous system development. There are also multiple genes that are associated with breast, ovarian and prostate cancers which suggests there may be a shared aetiology. Most of the low-penetrance genes that are underlying these 'shared' cancers are largely unknown. This project aims to identify the candidate functional variants, and their putative role across 'shared cancers'.
See Stephen's description of his project at: http://www.open.edu/openlearn/science-maths-technology/biology/big-data-and-bioinformatics-powerful-tools-decoding-dna
Winner of the 3 Minute Thesis (3MT) OU Student Conference 2019
PhD student: Perla Pucci
Title: Epigenetics and non-coding RNAs as novel therapeutic targets for incurable neuroendocrine prostate cancer.
Funding: The Open University
Highly commendable award in the 3 Minute Thesis (3MT) OU Student Conference 2019
OU Undergraduate projects (voluntary research)
Title: Identification of lncRNAs that drive liver cancer development and metastases using the cBioPortal database and R programming.
Title: Identification of variants in Neuromyelitis optica spectrum disorder (NMOSD), Neuromyelitis optica (NMO) and related disorders.
Identification of regulatory DNA variants in apoptosis genes associated with breast cancer risk, Yorkshire Cancer Research, pump prime award, co-applicant 80%, 2012-13
The role of apoptosis genes in breast cancer susceptibility, Wellcome Trust Value in People award, principal investigator, 2009.
I have taught on Undergraduate and Graduate degree programmes in the Medical School of Sheffield University, and in Clinical Sciences at the University of Bradford; designing and delivering active learning into the curriculums. I now use active learning strategies in the design and production of eLearning modules at the Open University:
SK299 Human biology (level 2, 60 credits)
SDK100 Science and health (level 1, 60 credits)
PGC HEP, Postgraduate Certificate in Higher Education Practice, University of Bradford, 2016
Fellow of the Higher education Academy (FHEA) from 2016
Associate Fellow of the Higher Education (AFHEA) from 2013
In collaboration with Professor Angela Cox (Breast Cancer Consortium, UK) we are currently aiming to work towards developing personalised screening tools (blood tests) and therapies, including identifying novel target therapies; by characterising DNA and RNA variants and identifying novel putative variants that are functional in the risk of breast cancer and other cancers with shared aetiology.
Professor Angela Cox, University of Sheffield, UK
LncRNA HORAS5 Promotes Taxane Resistance in Castration-Resistant Prostate Cancer via a BCL2A1-dependent Mechanism (2020)
Pucci, Perla; Venalainen, Erik; Alborelli, Ilaria; Quagliata, Luca; Hawkes, Cheryl; Mather, Rebecca; Romero, Ignacio A; Rigas, Sushila; Wang, Yuzhuo and Crea, Francesco
Epigenomics ((In Press))
HORAS5 promotes cabazitaxel resistance in castration resistant prostate cancer via a BCL2A1-dependent survival mechanism (2019-10-01)
Pucci, P.; Venalainen, E.; Alborelli, I.; Quagliata, L.; Mather, R.; Rigas, S.; Romero, I.; Wang, Y. and Crea, F.
Annals of Oncology, 30(5) (v798)
T-type calcium channels drive the proliferation of androgen-receptor negative prostate cancer cells (2019-09-15)
Silvestri, Roberto; Pucci, Perla; Venalainen, Erik; Matheou, Chrysanthi; Mather, Rebecca; Chandler, Stephen; Aceto, Romina; Rigas, Sushila; Wang, Yuzhuo; Rietdorf, Katja; Bootman, Martin and Crea, Francesco
The Prostate, 79(13) (pp. 1580-1586)
EZH2 Single Nucleotide Variants (SNVs): Diagnostic and Prognostic Role in 10 Solid Tumor Types (2017-12-12)
Paolicchi, Elisa; Fornaro, Lorenzo; Landi, Stefano; Rigas, Sushilaben and Crea, Francesco
Epigenomes, 1, Article 18(3)
Discordant Haplotype Sequencing Identifies Functional Variants at the 2q33 Breast Cancer Risk Locus (2016-04-01)
Camp, Nicola J.; Lin, Wei-Yu; Bigelow, Alex; Burghel, George J.; Mosbruger, Timothy L.; Parry, Marina A.; Waller, Rosalie G.; Rigas, Sushilaben H.; Tai, Pei-Yi; Berrett, Kristofer; Rajamanickam, Venkatesh; Cosby, Rachel; Brock, Ian W.; Jones, Brandt; Connley, Dan; Sargent, Robert; Wang, Guoying; Factor, Rachel E.; Bernard, Philip S.; Cannon-Albright, Lisa; Knight, Stacey; Abo, Ryan; Werner, Theresa L.; Reed, Malcolm W. R.; Gertz, Jason and Cox, Angela
Cancer Research, 76(7) (pp. 1916-1925)
Targeted DNA and RNA sequencing identifies breast cancer risk variants associated with differential expression of CASP8 and CFLAR/CASP10 (2014-10)
Camp, Nicola J.; Lin, Wei-Yu; Bigelow, Alex; Parry, Marina A.; Mosbruger, Tim; Burghel, George; Rajamanickam, Venkatesh; Rigas, Sushilaben H.; Cosby, Rachel; Connley, Dan; Wang, Guoying; George, Tresa; Waller, Rosalie; Cannon-Albright, Lisa A.; Jones, Brandt; Sargent, Rob; Reed, Malcolm W. R. and Cox, Angela
Cancer Research, 74, Article 3267(19 (Supp))
Fine-Mapping CASP8 Risk Variants in Breast Cancer (2012-01)
Camp, Nicola J.; Parry, Marina; Knight, Stacey; Abo, Ryan; Elliott, Graeme; Rigas, Sushilaben H.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; McBurney, Helen; Latif, Ayse; Newman, William G.; Cannon-Albright, Lisa A.; Evans, D. Gareth and Cox, Angela
Cancer Epidemiology, Biomarkers & Prevention, 21(1) (pp. 176-181)
A Breast Cancer Risk Haplotype in the Caspase-8 Gene (2009-04)
Shephard, Neil Duncan; Abo, Ryan; Rigas, Sushila Harkisandas; Frank, Bernd; Lin, Wei-Yu; Brock, Ian Wallace; Shippen, Adam; Balasubramanian, Sabapathy Prakash; Reed, Malcolm Walter Ronald; Bartram, Claus Rainer; Meindl, Alfons; Schmutzler, Rita Katharina; Engel, Christopher; Burwinkel, Barbara; Cannon-Albright, Lisa Anne; Allen-Brady, Kristina; Camp, Nicola Jane and Cox, Angela
Cancer Research, 69(7) (pp. 2724-2728)
The CASP8 -652 6N del promoter polymorphism and breast cancer risk: a multicenter study (2008-09)
Frank, Bernd; Rigas, Sushila H.; Bermejo, Justo Lorenzo; Wiestler, Miriam; Wagner, Kerstin; Hemminki, Kari; Reed, Malcolm W.; Sutter, Christian; Wappenschmidt, Barbara; Balasubramanian, Sabapathy P.; Meindl, Alfons; Kiechle, Marion; Bugert, Peter; Schmutzler, Rita K.; Bartram, Claus R.; Justenhoven, Christina; Ko, Yon-Dschun; Brüning, Thomas; Brauch, Hiltrud; Hamann, Ute; Pharoah, Paul P. D.; Dunning, Alison M.; Pooley, Karen A.; Easton, Douglas F.; Cox, Angela and Burwinkel, Barbara
Breast Cancer Research and Treatment, 111(1) (pp. 139-144)
Frequent p16-Independent Inactivation of p14ARF in Human Melanoma (2008-06-04)
Freedberg, Daniel E.; Rigas, Sushila H.; Russak, Julie; Gai, Weiming; Kaplow, Margarita; Osman, Iman; Turner, Faye; Randerson-Moor, Juliette A.; Houghton, Alan; Busam, Klaus; Bishop, D. Timothy; Bastian, Boris C.; Newton-Bishop, Julia A. and Polsky, David
Journal of the National Cancer Institute, 100(11) (pp. 784-795)
Features associated with germline CDKN2A mutations: a GenoMEL study of melanoma-prone families from three continents (2007-02)
Goldstein, Alisa M.; Chan, May; Harland, Mark; Hayward, Nicholas K.; Demenais, Florence; Bishop, D. Timothy; Azizi, Esther; Bergman, Wilma; Bianchi-Scarra, Giovanna; Bruno, William; Calista, Donata; Cannon Albright, Lisa A.; Chaudru, Valerie; Chompret, Agnes; Cuellar, Francisco; Elder, David E.; Ghiorzo, Paola; Gillanders, Elizabeth M.; Gruis, Nelleke A.; Hansson, Johan; Hogg, David; Holland, Elizabeth A.; Kanetsky, Peter A.; Kefford, Richard F.; Landi, Maria Teresa; Lang, Julie; Leachman, Sancy A.; MacKie, Rona M.; Magnusson, Veronica; Mann, Graham J.; Newton Bishop, Julia; Palmer, Jane M.; Puig, Susana; Puig-Butille, Joan A.; Stark, Mitchell; Tsao, Hensin; Tucker, Margaret A.; Whitaker, Linda; Yakobson, Emanuel; The Lund Melanoma Study Group, ; The Melanoma Genetics Consortium (GenoMEL), and Mistry, Sushila
Journal of Medical Genetics, 44(2) (pp. 99-106)
High-risk Melanoma Susceptibility Genes and Pancreatic Cancer, Neural System Tumors, and Uveal Melanoma across GenoMEL (2006-10)
Goldstein, Alisa M.; Chan, May; Harland, Mark; Gillanders, Elizabeth M.; Hayward, Nicholas K.; Avril, Marie-Francoise; Azizi, Esther; Bianchi-Scarra, Giovanna; Bishop, D. Timothy; Bressac-de Paillerets, Brigitte; Bruno, William; Calista, Donato; Cannon Albright, Lisa A.; Demenais, Florence; Elder, David E.; Ghiorzo, Paola; Gruis, Nelleke A.; Hansson, Johan; Hogg, David; Holland, Elizabeth A.; Kanetsky, Peter A.; Kefford, Richard F.; Landi, Maria Teresa; Lang, Julie; Leachman, Sancy A.; MacKie, Rona M.; Magnusson, Veronica; Mann, Graham J.; Niendorf, Kristin; Newton Bishop, Julia; Palmer, Jane M.; Puig, Susana; Puig-Butille, Joan A.; de Snoo, Femke A.; Stark, Mitchell; Tsao, Hensin; Tucker, Margaret A.; Whitaker, Linda; Yakobson, Emanuel; The Lund Melanoma Study Group, ; The Melanoma Genetics Consortium (GenoMEL), and Mistry, Sushila
Cancer Research, 66(20) (pp. 9818-9828)
Prevalence of 9p21 Deletions in UK Melanoma Families (2005-11)
Mistry, Sushila H.; Taylor, Claire; Randerson-Moor, Juliette A.; Harland, Mark; Turner, Faye; Barrett, Jennifer H.; Whitaker, Linda; Jenkins, Robert B.; Knowles, Margaret A.; Newton Bishop, Julia A. and Bishop, D. Timothy
Genes, Chromosomes & Cancer, 44(3) (pp. 292-300)
A deep intronic mutation in CDKN2A is associated with disease in a subset of melanoma pedigrees (2001-11-01)
Harland, Mark; Mistry, Sushila; Bishop, D. Timothy and Newton Bishop, Julia A.
Human Molecular Genetics, 10(23) (pp. 2679-2686)
Identification of candidate genes that may function in ER- breast cancer (2018)
Chandler, Stephen; Crea, Francesco; Hirst, Mark; Cox, Angela and Rigas, Sushila
In : BACR Conference: Response and Resistance in Cancer Therapy (10-12 Sep 2018, University of Kent, Canterbury)
Identification of putative functional genes in breast and other cancers with potentially shared aetiology (2017-11-23)
Chandler, Stephen; Crea, Francesco; Hirst, Mark; Cox, Angela and Rigas, Sushilaben
In : The Human Genome in Healthcare (23-24 Nov 2017, The Royal Society, London, UK)
Identification of a long non-coding RNA that mediates response to therapy in castration-resistant prostate cancer (2017)
Pucci, Perla; Venalainen, Erik; Mather, Rebecca; Xue, Hui; Rigas, Sushila; Romero, Ignacio A; Wang, Yuzho and Crea, Francesco
In : 3rd International Cancer Symposium (25-27 Sep 2017, Lyon, France)
Association of the TNFRSF10A and TNFRSF10B Gene Region on Chromosome 8 with Breast Cancer Risk (2011-09-01)
Rigas, S.; Elliot, G.; Brock, I.; Parry, M.; Abo, R.; Knight, S.; Burghel, G.; Lin, W. Y.; Reed, M. W.; Camp, N. J. and Cox, A.
In : British Human Genetics Conference (Sep 2011) (S41-S41)
Assessing the functional role of caspase-8 gene variants in breast cancer (2010-05-18)
Rigas, S. H.; Parry, M.; Reed, M. W.; Camp, N. and Cox, A.
In : Breast Cancer Research 2010 (18 May 2010, London, UK)
Abstract 2844: Association of genetic variants in TNFRSF10B and breast cancer (2010-04)
Abo, Ryan P.; Parry, Marina; Rigas, Sushila H.; Cox, Angela and Camp, Nicola J.
In : Proceedings: AACR 101st Annual Meeting 2010 (17-21 Apr 2010, Washington, DC)
Abstract# 2556: An investigation of the role of the caspase-8 gene in prostate and colon cancer susceptibility using a SNP-tagging approach (2009)
Cox, Angela; Lin, Wei-Yu; Elliott, Graeme; Rigas, Sushila; Bishop, D Timothy; Cannon-Albright, Lisa; Cai, Zheng; Camp, Nicola; Neal, David; Donovan, Jenny and Hamdy, Freddie
In : Proc Am Assoc Cancer Res; 2009 (18-22 Apr 2009, Denver, Colorado)
The functional Role of CASP8 D302H and Other Apoptosis Gene Variants In Breast Cancer (2009)
Rigas, Sushila H.; Parry, Marina; Reed, Malcolm W. and Cox, Angela
In : British Human Genetics Conference (31 Aug - 2 Sep 2009, University of Warwick) (S108)
Role of CASP8 D302H and Other Apoptosis Gene Variants in Breast Cancer (2006-11-01)
Rigas, Sushila; Rafii, S; Shippen, AL; MacPherson, G; Balasubramanian, S; Reed, MW and Cox, A
In : Breast cancer research: the past and the future (1 Nov 2006, The Royal Society, London, UK)
The Role Of p14ARF In Familial And Sporadic Melanoma (2004)
Mistry, Sushilaben Harkisandas
PhD thesis University of Leeds