![Elaine Dunlop BSc (Hons) PhD FHEA](https://profiles-cardiff.imgix.net/attachments/2420?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr Elaine Dunlop
BSc (Hons) PhD FHEA
Lecturer
- DunlopEA@cardiff.ac.uk
- +44 29206 87785
- Cancer Genetics Building, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
- Available for postgraduate supervision
Overview
'Working towards tailored therapies for inherited diseases and cancer'
My research centres on the inherited conditions, Tuberous Sclerosis Complex (TSC) and Birt-Hogg-Dubé (BHD) syndrome where patients are predisposed to develop cysts and tumours. I aim to understand what is malfunctioning in these cells at a molecular level, with the goal of identifying weaknesses which could be specifically targeted by therapies. I also have an interest in intercellular communication and the microenvironment, exploring how these facets of tumour biology can support tumour growth. As there is crossover between the altered growth pathways observed in these genetic diseases and the pathways which are at fault in sporadic cancer, these future treatments could also be effective for the wider cancer community. Therefore, through a better understanding of disease processes we can work towards stratifying patients based on the genetics of their disease and treating them with appropriately tailored therapies.
Professional Network Sites
- ResearchGate: https://www.researchgate.net/profile/Elaine_Dunlop
- Publons: https://publons.com/researcher/1555538/elaine-a-dunlop
- ORCiD: https://orcid.org/0000-0002-9209-7561
Publication
2023
- Bhaoighill, M. N., Falcón-Pérez, J. M., Royo, F., Tee, A., Webber, J. and Dunlop, E. 2023. Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers. Journal of Extracellular Vesicles 12(6), article number: 12336. (10.1002/jev2.12336)
2021
- Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S. and Dunlop, E. 2021. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy 17(1), pp. 1-382. (10.1080/15548627.2020.1797280)
2019
- Ni Bhaoighill, M. and Dunlop, E. A. 2019. Mechanistic target of rapamycin inhibitors: successes and challenges as cancer therapeutics. Cancer Drug Resistance 2019(2), pp. 1069-1085. (10.20517/cdr.2019.87)
2018
- Johnson, C. E. et al. 2018. Loss of tuberous sclerosis complex 2 sensitizes tumors to nelfinavir−bortezomib therapy to intensify endoplasmic reticulum stress-induced cell death. Oncogene 37, pp. 5913-5925. (10.1038/s41388-018-0381-2)
- McCann, H., Johnson, C., Errington, R., Davies, D. M., Dunlop, E. and Tee, A. 2018. Energy stress-mediated cytotoxicity in tuberous sclerosis complex 2-deficient cells with nelfinavir and mefloquine treatment. Cancers 10(10), pp. -., article number: 375. (10.3390/cancers10100375)
- Yeung, V. et al. 2018. Rab35-dependent extracellular nanovesicles are required for induction of tumour supporting stroma. Nanoscale 10(18), pp. 8547-8559. (10.1039/C8NR02417K)
2017
- Carroll, B. and Dunlop, E. A. 2017. The lysosome: a crucial hub for AMPK and mTORC1 signalling. Biochemical Journal 474(9), pp. 1453-1466. (10.1042/BCJ20160780)
- Dunlop, E. A., Johnson, C., Wiltshire, M., Errington, R. J. and Tee, A. 2017. Targeting protein homeostasis with nelfinavir/salinomycin dual therapy effectively. Oncotarget (10.18632/oncotarget.16232)
2016
- Dodd, K. M. and Dunlop, E. A. 2016. Tuberous sclerosis—A model for tumour growth. Seminars in Cell and Developmental Biology 52, pp. 3-11. (10.1016/j.semcdb.2016.01.025)
- Carroll, B. et al. 2016. Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity. eLife 5, pp. -., article number: e11058. (10.7554/eLife.11058)
2014
- Dunlop, E. and Tee, A. 2014. mTOR and autophagy: a dynamic relationship governed by nutrients and energy. Seminars in Cell and Developmental Biology 36, pp. 121-129. (10.1016/j.semcdb.2014.08.006)
- Yan, M. et al. 2014. The tumor suppressor folliculin regulates AMPK-dependent metabolic transformation. Journal of Clinical Investigation 124(6), pp. 2640-2650. (10.1172/JCI71749)
- Dunlop, E. et al. 2014. FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation. Autophagy 10(10), pp. 1749-1760. (10.4161/auto.29640)
2013
- Zhang, J. et al. 2013. A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS. Nature Cell Biology 15(10), pp. 1186-1195. (10.1038/ncb2822)
2012
- Thomas, L., Richards, M., Mort, M. E., Dunlop, E. A., Cooper, D. N. and Upadhyaya, M. 2012. Assessment of the potential pathogenicity of missense mutations identified in the GTPase-activating protein (GAP)-related domain of the neurofibromatosis type-1 (NF1) gene. Human Mutation 33(12), pp. 1687-1696. (10.1002/humu.22162)
2011
- Dunlop, E. A., Hunt, D. K., Acosta-Jaquez, H. A., Fingar, D. C. and Tee, A. 2011. ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding. Autophagy 7(7), pp. 737-747. (10.4161/auto.7.7.15491)
- Dunlop, E. A. et al. 2011. Determining the pathogenicity of patient-derived TSC2 mutations by functional characterization and clinical evidence. European Journal of Human Genetics 19(7), pp. 789-795. (10.1038/ejhg.2011.38)
- Preston, R. S. et al. 2011. Absence of the Birt-Hogg-Dubé gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility. Oncogene 30(10), pp. 1159-1173. (10.1038/onc.2010.497)
2010
- Soliman, G. A., Acosta-Jaquez, H. A., Dunlop, E. A., Ekim, B., Maj, N. E., Tee, A. and Fingar, D. C. 2010. mTOR Ser-2481 Autophosphorylation Monitors mTORC-specific Catalytic Activity and Clarifies Rapamycin Mechanism of Action. Journal of Biological Chemistry 285(11), pp. 7866-7879. (10.1074/jbc.M109.096222)
- Shi, Z., Hodges, V. M., Dunlop, E. A., Percy, M. J., Maxwell, A. P., El-Tanani, M. and Lappin, T. R. J. 2010. Erythropoietin-induced activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK pathways promotes malignant cell behavior in a modified breast cancer cell line. Molecular Cancer Research 8(4), pp. 615-626. (10.1158/1541-7786.MCR-09-0264)
2009
- Dunlop, E. A., Dodd, K. M., Seymour, L. A. and Tee, A. 2009. Mammalian target of rapamycin complex 1-mediated phosphorylation of eukaryotic initiation factor 4E-binding protein 1 requires multiple protein-protein interactions for substrate recognition. Cellular Signalling 21(7), pp. 1073-1084. (10.1016/j.cellsig.2009.02.024)
- Dunlop, E. A. and Tee, A. 2009. Mammalian target of rapamycin complex 1: Signalling inputs, substrates and feedback mechanisms. Cellular Signalling 21(6), pp. 827-835. (10.1016/j.cellsig.2009.01.012)
2007
- Dunlop, E. A., Maxwell, A. P. and Lappin, T. R. J. 2007. Impaired downregulation following erythropoietin receptor activation in non-small cell lung carcinoma. Stem Cells 25(2), pp. 380-384. (10.1634/stemcells.2006-0452)
2006
- Brown, W. M. et al. 2006. Erythropoietin receptor expression in non-Small cell lung carcinoma: a question of antibody specificity. Stem Cells 25(3), pp. 718-722. (10.1634/stemcells.2006-0687)
- Dunlop, E. A., Percy, M. J., Boland, M. P., Maxwell, A. P. and Lappin, T. R. 2006. Induction of signalling in non-erythroid cells by pharmacological levels of erythropoietin. Neurodegenerative Diseases 3(1-2), pp. 94-100. (10.1159/000092099)
Articles
- Bhaoighill, M. N., Falcón-Pérez, J. M., Royo, F., Tee, A., Webber, J. and Dunlop, E. 2023. Tuberous Sclerosis Complex cell-derived EVs have an altered protein cargo capable of regulating their microenvironment and have potential as disease biomarkers. Journal of Extracellular Vesicles 12(6), article number: 12336. (10.1002/jev2.12336)
- Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S. and Dunlop, E. 2021. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy 17(1), pp. 1-382. (10.1080/15548627.2020.1797280)
- Ni Bhaoighill, M. and Dunlop, E. A. 2019. Mechanistic target of rapamycin inhibitors: successes and challenges as cancer therapeutics. Cancer Drug Resistance 2019(2), pp. 1069-1085. (10.20517/cdr.2019.87)
- Johnson, C. E. et al. 2018. Loss of tuberous sclerosis complex 2 sensitizes tumors to nelfinavir−bortezomib therapy to intensify endoplasmic reticulum stress-induced cell death. Oncogene 37, pp. 5913-5925. (10.1038/s41388-018-0381-2)
- McCann, H., Johnson, C., Errington, R., Davies, D. M., Dunlop, E. and Tee, A. 2018. Energy stress-mediated cytotoxicity in tuberous sclerosis complex 2-deficient cells with nelfinavir and mefloquine treatment. Cancers 10(10), pp. -., article number: 375. (10.3390/cancers10100375)
- Yeung, V. et al. 2018. Rab35-dependent extracellular nanovesicles are required for induction of tumour supporting stroma. Nanoscale 10(18), pp. 8547-8559. (10.1039/C8NR02417K)
- Carroll, B. and Dunlop, E. A. 2017. The lysosome: a crucial hub for AMPK and mTORC1 signalling. Biochemical Journal 474(9), pp. 1453-1466. (10.1042/BCJ20160780)
- Dunlop, E. A., Johnson, C., Wiltshire, M., Errington, R. J. and Tee, A. 2017. Targeting protein homeostasis with nelfinavir/salinomycin dual therapy effectively. Oncotarget (10.18632/oncotarget.16232)
- Dodd, K. M. and Dunlop, E. A. 2016. Tuberous sclerosis—A model for tumour growth. Seminars in Cell and Developmental Biology 52, pp. 3-11. (10.1016/j.semcdb.2016.01.025)
- Carroll, B. et al. 2016. Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity. eLife 5, pp. -., article number: e11058. (10.7554/eLife.11058)
- Dunlop, E. and Tee, A. 2014. mTOR and autophagy: a dynamic relationship governed by nutrients and energy. Seminars in Cell and Developmental Biology 36, pp. 121-129. (10.1016/j.semcdb.2014.08.006)
- Yan, M. et al. 2014. The tumor suppressor folliculin regulates AMPK-dependent metabolic transformation. Journal of Clinical Investigation 124(6), pp. 2640-2650. (10.1172/JCI71749)
- Dunlop, E. et al. 2014. FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation. Autophagy 10(10), pp. 1749-1760. (10.4161/auto.29640)
- Zhang, J. et al. 2013. A tuberous sclerosis complex signalling node at the peroxisome regulates mTORC1 and autophagy in response to ROS. Nature Cell Biology 15(10), pp. 1186-1195. (10.1038/ncb2822)
- Thomas, L., Richards, M., Mort, M. E., Dunlop, E. A., Cooper, D. N. and Upadhyaya, M. 2012. Assessment of the potential pathogenicity of missense mutations identified in the GTPase-activating protein (GAP)-related domain of the neurofibromatosis type-1 (NF1) gene. Human Mutation 33(12), pp. 1687-1696. (10.1002/humu.22162)
- Dunlop, E. A., Hunt, D. K., Acosta-Jaquez, H. A., Fingar, D. C. and Tee, A. 2011. ULK1 inhibits mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding. Autophagy 7(7), pp. 737-747. (10.4161/auto.7.7.15491)
- Dunlop, E. A. et al. 2011. Determining the pathogenicity of patient-derived TSC2 mutations by functional characterization and clinical evidence. European Journal of Human Genetics 19(7), pp. 789-795. (10.1038/ejhg.2011.38)
- Preston, R. S. et al. 2011. Absence of the Birt-Hogg-Dubé gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility. Oncogene 30(10), pp. 1159-1173. (10.1038/onc.2010.497)
- Soliman, G. A., Acosta-Jaquez, H. A., Dunlop, E. A., Ekim, B., Maj, N. E., Tee, A. and Fingar, D. C. 2010. mTOR Ser-2481 Autophosphorylation Monitors mTORC-specific Catalytic Activity and Clarifies Rapamycin Mechanism of Action. Journal of Biological Chemistry 285(11), pp. 7866-7879. (10.1074/jbc.M109.096222)
- Shi, Z., Hodges, V. M., Dunlop, E. A., Percy, M. J., Maxwell, A. P., El-Tanani, M. and Lappin, T. R. J. 2010. Erythropoietin-induced activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK pathways promotes malignant cell behavior in a modified breast cancer cell line. Molecular Cancer Research 8(4), pp. 615-626. (10.1158/1541-7786.MCR-09-0264)
- Dunlop, E. A., Dodd, K. M., Seymour, L. A. and Tee, A. 2009. Mammalian target of rapamycin complex 1-mediated phosphorylation of eukaryotic initiation factor 4E-binding protein 1 requires multiple protein-protein interactions for substrate recognition. Cellular Signalling 21(7), pp. 1073-1084. (10.1016/j.cellsig.2009.02.024)
- Dunlop, E. A. and Tee, A. 2009. Mammalian target of rapamycin complex 1: Signalling inputs, substrates and feedback mechanisms. Cellular Signalling 21(6), pp. 827-835. (10.1016/j.cellsig.2009.01.012)
- Dunlop, E. A., Maxwell, A. P. and Lappin, T. R. J. 2007. Impaired downregulation following erythropoietin receptor activation in non-small cell lung carcinoma. Stem Cells 25(2), pp. 380-384. (10.1634/stemcells.2006-0452)
- Brown, W. M. et al. 2006. Erythropoietin receptor expression in non-Small cell lung carcinoma: a question of antibody specificity. Stem Cells 25(3), pp. 718-722. (10.1634/stemcells.2006-0687)
- Dunlop, E. A., Percy, M. J., Boland, M. P., Maxwell, A. P. and Lappin, T. R. 2006. Induction of signalling in non-erythroid cells by pharmacological levels of erythropoietin. Neurodegenerative Diseases 3(1-2), pp. 94-100. (10.1159/000092099)
Research
Research overview
My research focuses on the signalling pathways underlying genetic diseases and cancer. Much of my work is concentrated on the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway which controls cell growth, and is disrupted in a number of genetic tumour-disposition syndromes, such as Tuberous Sclerosis Complex (TSC) and Birt-Hogg-Dubé (BHD) Syndrome, as well as in sporadic cancer. My research interests are all linked to signalling mechanisms that are drivers of cancer, including processes such as autophagy, metastasis and cell-to-cell communication. Recently I have expanded my research to examine the contribution of the microenvironment to genetic disease and am exploring potential predictive biomarkers of disease.
The overall aim of my research is to gain sufficient understanding of the defects underlying TSC and BHD to identify pathways that could be targeted to bring therapeutic benefit to patients. Due to the crossover between the altered signalling pathways seen in TSC, BHD and cancer, the broader scope of my future research is to determine whether these therapies are also effective on stratified sporadic cancers. I work closely with the wider TSC research team at Cardiff, which includes clinicians and geneticists to find cellular mechanisms that can be exploited for potential therapy. I also have strong collaborations with the Cardiff University Tissue Microenvironment Group and Swansea University, supporting extracellular vesicle projects.
Scientific Contribution
- The role of extracellular vesicles and the microenvironment in TSC. My recent work has explored the composition and function of extracellular vesicles released by TSC cells. This has revealed that blood plasma vesicles contain potential biomarkers for TSC and that intercellular signalling via extracellular vesicles can module cells of the microenvironment.
- Therapeutic targeting of mTORC1-driven cells. I have used knowledge of the points of stress in TSC-deficient cells to identify potential therapeutic targets. We have explored the use of chemical agents and the repositioning of FDA approved drugs in order to preferentially induce cell death in TSC-deficient cells. We discovered that a combination of nelfinavir and bortezomib selectively kills TSC2-deficient cell lines in vitro and reduces tumour volume in vivo, indicating that targeting endoplasmic reticulum stress in combination with proteasomal inhibition could be a viable strategy to treat TS patients. The combination was also effective in sporadic cancer cell lines with mTORC1 hyperactivity, indicating potential broader applications.
- Exploring mTORC1 cellular signalling mechanisms. My research has better characterized the interactions between the various proteins involved in mTORC1 and we were the first to identify a novel feedback loop allowing the ULK1 kinase involved in autophagy to turn off mTORC1 signalling through specific phosphorylation events. Additionally, two collaborative publications have analysed the role of the TSC proteins at the peroxisome and the influence of arginine on the TSC2-Rheb signalling axis. This work has enhanced our understanding of the mTORC1 signalling network which is known to be dysregulated in many human diseases.
- Understanding Birt-Hogg-Dubé (BHD) Syndrome. The cellular function of the tumour suppressor protein, folliculin (FLCN), responsible for BHD syndrome is not well characterized. Over the course of my Myrovlytis Trust Fellowship, I revealed altered homeostatic pathways in FLCN-deficient cells, including working with collaborators to show that FLCN plays a role in AMPK signalling, leading to mitochondrial biogenesis, increased ROS production and a conversion towards Warburg metabolic reprogramming. Additionally, I discovered that FLCN is necessary for efficient basal autophagy, interacts with two key components of the autophagy machinery and is a new substrate of ULK1. We also confirmed autophagy defects in tumour samples from BHD patients. This work has helped elucidate the function of FLCN and provide an insight into the homeostatic changes in the cells of BHD patients.
Teaching
I am the route lead for the intercalated BSc in Genomic Medicine. Interested students are welcome to contact me for more information about the course.
Within the Genomic Medicine course, I am also:
- Module lead for Fundamentals of Genetics and Genomics
- Project co-ordinator for Genomic Medicine research projects
I contribute to undergraduate MBBCh C21 curriculum delivery through:
- Year 1 – Student Selected Component, Literature Review
- Year 2 – Case Based Learning Facilitator
- Year 2 - Student Selected Component
- Year 4 - Student Selected Component project supervisor
I also contribute to Medical Pharmacology and other intercalated BSc Programmes
- Molecular Genetics and Cell Biology module
- Critical Analysis and Scientific Methods module
- Research Supervisor to laboratory based Intercalated Projects
I am a personal tutor for MBBCh and BSc Genomic Medicine students.
I am a Fellow of the Higher Education Academy.
I am a STEM Ambassador, contributing to outreach activities involving school children and patient groups. These include the School of Medicine 'Science in Health Live' event and the Life Sciences Challenge.
Biography
Education and Qualifications
2019 FHEA - Fellow of the Higher Education Academy
2006 PhD (Centre for Cancer Research and Cell Biology) Queen’s University, Belfast
2003 BSc (Hons) Biochemistry, First Class, Queen’s University, Belfast
Awarded Tim Bramley Prize (Top Biochemistry student, 2003) & John Sinclair Porter Scholarship (2001)
Career Overview
- Jan 2019 – present Lecturer, Division of Cancer & Genetics/Centre for Medical Education, Cardiff University
- Jul 2015 – Jan 2019 Research Fellow, Division of Cancer & Genetics, Cardiff University
- Mar 2013 – Jul 2015 Research Associate, Institute of Cancer & Genetics, Cardiff University
- Jan 2011 – Feb 2013 Myrovlytis Trust Research Fellow, Institute of Cancer & Genetics, Cardiff University
- May 2007 – Dec 2010 Research Associate, Institute of Medical Genetics, Cardiff University
- Oct 2006 – Apr 2007 Special Research Scholar, Haematology Research, Queen’s University, Belfast
Professional memberships
- 2020 - present Member of the UK Society for Extracellular Vesicles
- 2019 - present Fellow of the Higher Education Academy
- 2016 Welsh Crucible Participant
- 2016 - present Member of the European Association for Cancer Research
- 2014 Associate Fellow of the Higher Education Academy
Committees and reviewing
- Editorial Board member, PeerJ
- Editorial Board member, Cancers
- Reviewer for journals including Autophagy, British Journal of Cancer, Scientific Reports, as well as several MDPI journals.
Engagement
Outreach activities
My first involvement in public engagement was through the Beacon Researchers in Schools scheme in 2010, running Genetics workshops at Duffryn High School, Newport. Following this, I became a STEM Ambassador, and have regularly undertaken a range of activities since.
I have contributed to outreach activities organised by others for schoolchildren, such as the School of Medicine ‘Life Sciences Challenge’ and 'Science in Health Live' events. I have also collaborated with teachers to deliver bespoke events, such as a PCR/gel electrophoresis experience and careers talks.
I have participated in events for the general public, including Wales Cancer Research Centre’s ‘How do we develop new cancer drugs?’ event in 2017 and 'Pint of Science' in Cardiff in 2019. I have also spoken about my research to patient groups, such as at the Tuberous Sclerosis Association’s Big Day 2018 and the TSA Welsh Info Day 2019 and 2020.