Senior Lecturer in Biochemistry
I am a Cell Biologist and Biochemist with a special focus on mechanisms that regulate the growth and metastasis of cancer. I teach undergraduate biochemistry and have an active research interest in understanding how stress response mechanisms, such as the unfolded protein response and autophagy, affect the survival of cancer cells and how these processes may be targeted to prevent a cancer developing or specifically kill cancer cells when they occur.
Teaching and supervision
- HCS112 Chemistry for the Biosciences
- HCS304 Clinical Biochemistry
Research interests for potential research students
My research interests relate to the activation and regulation of cellular stress response mechanisms. These include:
- The effect of endocannabinoid deficiency and cannabinoid treatment on endoplasmic reticulum (ER) stress and the unfolded protein response (UPR).
- The effect of cannabinoids on lipid metabolism and lipid-mediated activation of ER stress.
- How regulation of ER stress and the UPR affects susceptibility to oncogene-induced transformation of normal cells.
The endocannabinoid system regulates a diverse range of physiological processes including motor control, motivation behaviour, pain, emotional responsiveness, and food intake. But on a cellular level the endocannabinoid system effects mechanisms such as energy homeostasis and the regulation of stress-response pathways that impact on the cell death/survival response of a cell during periods of environmental change or genetic mutation.
Cellular stress is defined as the damage that occurs to proteins and organelles during normal homeostasis, which must be repaired for the cell to survive. If this damage is excessive or persistent it will overwhelm the cell’s stress response and repair mechanisms leading to cell death or senescence (permanent growth arrest).
By activating stress response mechanisms, the endocannabinoid system may determine the susceptibility of a normal cell to undergo transformation when they acquire a genetic mutation by regulating the conversion of stress signals to cell death or senescence signals. Alternatively, endocannabinoid deficiency may reduce the activity of these stress response mechanisms allowing oncogene-induced stress to persist and for transformation to occur. Therefore, exogenous treatment of cancer with plant derived cannabinoids (or specific activation of cannabinoid-induced mechanisms) may re-establish the inducibility of stress-mediated cell death mechanisms and provide a more effective treatment option for patients with currently incurable tumours.
Therefore, my research aims to investigate the effect of endocannabinoids and exogenous cannabinoids on activation of stress-responses and cell death pathways. We have previously shown that cannabinoid treatment effectively induces apoptosis (programmed cell death) of melanoma skin cancer cells, and ongoing work aims to understand the mechanisms regulating cannabinoid-induced cell death to identify specific target to more precisely kill cancer cells.
Cosgarea, Ioana, McConnell, A, Ewen, T, Tang, D, Hill, David, Anagnostou, M, Elias, M, Ellis, RA, Murray, A, Spender, L, Giglio, P, Gagliardi, M, Greenwood, A, Piacentini, M, Inman, G, Fimia, G M, Corazzari, M, Armstrong, Jane and Lovat, P (2021) Melanoma secretion of transforming growth factor-β2 leads to loss of epidermal AMBRA1 threatening epidermal integrity and facilitating tumour ulceration. British Journal of Dermatology. ISSN 0007-0963
Hill, David, Cosgarea, Ioana, Reynolds, Nick, Lovat, Penny and Armstrong, Jane (2021) Research Techniques Made Simple: Analysis of Autophagy in the Skin. The Journal of investigative dermatology, 141 (1). 5-9.e1. ISSN 1523-1747
Verykiou, S., Alexander, M., Edwards, N., Plummer, R., Chaudhry, B., Lovat, P.E. and Hill, David (2019) Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma. British Journal of Dermatology, 180 (2). pp. 346-356. ISSN 0007-0963
Hill, David, Chen, Lanpeng, Snaar-Jagalska, Ewe and Chaudhry, Bill (2018) Embryonic zebrafish xenograft assay of human cancer metastasis. F1000Research, 7. p. 1682. ISSN 2046-1402
Beaumont, Kimberley A., Hill, David, Daignault, Sheena M., Lui, Goldie Y.L., Sharp, Danae M., Gabrielli, Brian, Weninger, Wolfgang and Haass, Nikolas K. (2016) Cell Cycle Phase-Specific Drug Resistance as an Escape Mechanism of Melanoma Cells. Journal of Investigative Dermatology, 136 (7). pp. 1479-1489. ISSN 0022-202X
Hill, David, Robinson, Neil D. P., Caley, Matthew P., Chen, Mei, O'Toole, Edel A., Armstrong, Jane, Przyborski, Stefan and Lovat, Penny E. (2015) A novel fully-humanised 3D skin equivalent to model early melanoma invasion. Molecular Cancer Therapeutics, 14 (9). pp. 2665-2675. ISSN 1535-7163
Haass, Nikolas K., Beaumont, Kimberley A., Hill, David, Anfosso, Andrea, Mrass, Paulus, Munoz, Marcia A., Kinjyo, Ichiko and Weninger, Wolfgang (2014) Real-time cell cycle imaging during melanoma growth, invasion, and drug response. Pigment Cell & Melanoma Research, 27 (5). pp. 764-776. ISSN 1755-1471