Newcastle University

Introduction

Following completion of my PhD at the University of Newcastle in the School of Biochemistry and Genetics, my post-doctoral studies between 2002-2008 were carried out in the Northern Institute for Cancer Research. I am currently a senior research associate based in Dermatological Sciences within the Institute of Cellular Medicine. My research incorporates two main areas; the regulation of stress signalling and cell death mechanisms in melanoma, and retinoid biology and pharmacology.

Qualifications

BSc(Hons) First Class in Biochemistry and Biological Chemistry, University of Nottingham, obtained in 1997.
PhD, School of Biochemistry and Genetics (supervisor: Professor SJ Yeaman), University of Newcastle Upon Tyne, obtained in 2001
Thesis title: Insulin signalling to glycogen synthesis in cultured human muscle cells.

Previous Positions

2000-2001: Research associate for Professor SJ Yeaman

Memberships

British Society for Investigative Dermatology (BSID)
British Association for Cancer Research (BACR)
European Association for Cancer Research (EACR)
European Cell Death Organisation (ECDO)

Honours and Awards

1. British Society of Investigative Dermatology New Investigator award (2011)
2. European Skin Research Foundation New Investigator award (2010) 
3. EACR travel fellowship to the Compultense University, Madrid (2010)
4. BSID travel award to attend and present at the 2010 annual meeting
5. BACR award to attend the 2009 International Melanoma Congress (Boston, USA)
6. Marie Curie Scholarships to attend the 14th and 15th conferences of the European Cell Death Organisation and Training course on 'Concepts and Methods in Programmed Cell Death' (2006 and 2007)

Research Interests

My primary research interest is focussed towards exploiting vulnerabilities in the signalling pathways which regulate autophagy and subsequently cell death or survival in melanoma. The identification of novel regulators of autophagy in melanoma will ultimately lead to an increased understanding of the role of autophagy in tumour development as well as facilitate the discovery of novel therapeutic targets and biomarkers of disease progression. I am also interested in autophagy in the context of the inflammatory skin disorder psoriasis.
In addition, I have an interest in retinoid biology and pharmacology involving study into the mechanism of action of both naturally-occurring retinoids, such as retinoic acid isomers, as well as synthetic retinoids eg. fenretinide. This has culminated in projects relating to the development and biological evaluation of novel inhibitors of retinoic acid metabolism for the treatment of cancer and dermatological diseases.

Other Expertise

Insulin signalling (to PI3-kinase, Akt, GSK3) and glucose metabolism in human skeletal muscle cells. Adenoviral expression systems to introduce wild-type or dominant-negative proteins into human muscle cells.

Current Work

Research currently in progress: (1) Investigating the relationship between autophagy and cell death in response to chemotherapeutic drugs for the treatment of melanoma, as well as in the context of melanoma development and metastasis, 2) Investigating the role of autophagy in the therapeutic response to anti-psoriatic drugs in both 2D and 3D skin models, 3) The development and biological evaluation of novel inhibitors of retinoic acid metabolism (CYP26 inhibitors) as cancer therapeutics, focussing on neuroblastoma.

Future Research

To facilitate the development of novel therapies for cancers and dermatological diseases, using both pharmacological and mechanistic approaches. This falls into two key areas:
1) Regulation of cell death mechanisms in cancer cells, cancer stem cells and their normal counterparts in the context of melanoma development and progression; delineation of these pathways will provide the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxics. 2) Development and biological evaluation of inhibiors of retinoic acid metabolism for cancer therapy, for example neuroblastoma or acute promyelocytic leukemia, and the treatment of skin diseases, such as psoriasis and acne.

Postgraduate Supervision

I supervise MRes and PhD students based within both Dermatological Sciences (melanoma biology) and the NICR (retinoid pharmacology)

Esteem Indicators

1. British Society Investigative Dermatology New Investigator award (2011)
2. European Skin Research Foundation New Investigator award (2010)
3. EACR Travel fellowship (2010)
4. Invited speaker, British Society for Investigative Dermatology Annual Meeting (2010)
5. Invited seminar, Complutense University, Madrid (2009)
6. BACR Travel Award (2009)
7. Elected onto Board of Directors (2009): North Eastern Skin Research Fund
8. Invited Speaker at the 11th Annual Advances in Neuroblastoma Research Meeting, Genoa, Italy (2004)
9. Invited Speaker at the UKCCSG Research Meeting, Newcastle UK (2005)Marie Curie Scholarships to attend the 14th and 15th conferences of the European Cell Death Organisation and Training course on 'Concepts and Methods in Programmed Cell Death' (2006 and 2007).
10. Journal Reviewer for Molecular Pharmacology, British Journal of Cancer, Current Cancer Drug Targets, International Journal of Cancer, Journal of Investigative Dermatology
11. Grant reviewer for The British Skin Foundation, Diabetes UK

Funding

Current and recent research funding from:
The British Skin Foundation
North Eastern Skin Research Fund
JGW Patterson
Cancer Research UK
MRC/RC-UK
Newcastle Healthcare Charity

Patents

Patent authorship: GB 0811091.8

Undergraduate Teaching

I have supervised 13 BSc Biomedical Science laboratory projects (including Physiology, Pharmacology, Immunology, and general Biomedical sciences), as well as Pharmacology students from Toulouse University, France. I am also involved in project assessment.

Postgraduate Teaching

I have supervised a number of Masters of Research laboratory projects, and assess MRes oral and written presentations as well as deliver a lecture for the MRes Medical and Molecular Biosciences course, titled 'Autophagy in Health and Disease' and assessment of a related essay assignment. In addition, I have or currently supervise PhD students, clinical research associates as well as post-doctoral researchers.

• Armstrong JL, Martin S, Illingworth NA, Jamieson D, Neilson A, Lovat PE, Redfern CPF, Veal GJ. The impact of retinoic acid treatment on the sensitivity of neuroblastoma cells to fenretinide. Oncology Reports 2012, 27(1), 293-298.
• Armstrong JL, Corazzari M, Martin S, Pagliarini V, Falasca L, Hill DS, Ellis N, Al Sabah S, Redfern CPF, Fimia GM, Piacentini M, Lovat PE. Oncogenic B-RAF Signaling in Melanoma Impairs the Therapeutic Advantage of Autophagy Inhibition. Clinical Cancer Research 2011, 17(8), 2216-2226.
• Gomaa MS, Bridgens CE, Aboraia AS, Veal GJ, Redfern CPF, Brancale A, Armstrong JL, Simons C. Small Molecule Inhibitors of Retinoic Acid 4-Hydroxylase (CYP26): Synthesis and Biological Evaluation of Imidazole Methyl 3-(4-(aryl-2-ylamino)phenyl)propanoates. Journal of Medicinal Chemistry 2011, 54(8), 2778-2791.
• Gomaa MS, Bridgens CE, Veal GJ, Redfern CPF, Brancale A, Armstrong JL, Simons C. Synthesis and Biological Evaluation of 3-(1H-Imidazol- and Triazol-1-yl)-2,2-dimethyl-3-[4-(naphthalen-2-ylamino)phenyl]propyl Derivatives as Small Molecule Inhibitors of Retinoic Acid 4-Hydroxylase (CYP26). Journal of Medicinal Chemistry 2011, 54(19), 6803-6811.
• Hiscutt EL, Hill DS, Martin S, Kerr R, Harbottle A, Birch-Machin M, Redfern CPF, Fulda S, Armstrong JL, Lovat PE. Targeting X-Linked Inhibitor of Apoptosis Protein to Increase the Efficacy of Endoplasmic Reticulum Stress-Induced Apoptosis for Melanoma Therapy. Journal of Investigative Dermatology 2010, 130(9), 2250-2258.
• Hill DS, Martin S, Armstrong JL, Flockhart R, Tonison JJ, Simpson DG, Birch-Machin MA, Redfern CPF, Lovat PE. Combining the endoplasmic reticulum stress-inducing agents bortezomib and fenretinide as a novel therapeutic strategy for metastatic melanoma. Clinical Cancer Research 2009, 15(4), 1192-1198.
• Flockhart RJ, Armstrong JL, Reynolds NJ, Lovat PE. NFAT signalling is a novel target of oncogenic BRAF in metastatic melanoma. British Journal of Cancer 2009, 101(8), 1448-1455.
• Lovat PE, Corazzari M, Armstrong JL, Martin S, Pagliarini V, Hill DS, Brown A, Piacentini M, Birch-Machin MA, Redfern CPF. Increasing melanoma cell death using inhibitors of protein disulfide isomerases to abrogate survival responses to endoplasmic reticulum stress. Cancer Research 2008, 68(13), 5363-5369.
• Gomaa MS, Armstrong JL, Bobillon B, Veal GJ, Brancale A, Redfern CPF, Simons C. Novel azolyl-(phenylmethyl)]aryl/heteroarylamines: Potent CYP26 inhibitors and enhancers of all-trans retinoic acid activity in neuroblastoma cells. Bioorganic and Medicinal Chemistry 2008, 16(17), 8301-8313.
• Ellis RA, Armstrong JL, Kirkham N, Ness T, Horswell S, Lovat PE. p62 as a biomarker of malignant melanoma. In: Meeting of the British Society for Investigative Dermatology. 2012, Exeter, UK: Wiley-Blackwell Publishing Ltd.
• Armstrong J, Ellis R, Polson H, Kirkham N, Horswell S, Tooze S, Lovat P. WIPI-1: a novel autophagy inhibitory protein in melanoma. In: Meeting of the British Society for Investigative Dermatology. 2012, Exeter, UK: Wiley-Blackwell Publishing Ltd.