Dr David Hill

• HCS112 Chemistry for the Biosciences 
• HCS304 Clinical Biochemistry

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.