Molecular Pharmacology and Pathology Program

Lab head: Des Richardson
Location: Pathology Department, Blackburn Building

Iron is essential for life and growth. While it is well known that iron deficiency can lead to anaemia it is generally not appreciated that iron is critical for the growth of all cells, particularly cancer cells. The Iron Metabolism and Chelation Program is concerned with understanding the basic processes of how tumour cells utilise and transport iron. This knowledge will lead to the development of therapies that can selectively starve tumour cells of iron and inhibit their growth. In addition, we are studying the mechanisms involved in iron loading in the inherited diseases I2-thalassaemia and Friedreich's ataxia.

Lab members: D Richardson (head), C Austin (pfellow), K Dixon (pfellow), P Jansson (pfellow), D Kalinowski (rfellow), D Lane (pfellow), K Loh (pfellow), D Lovejoy (rfellow), P Quach (pfellow), Y Suryo Rahmanto (rfellow), D Zhang (rfellow), M Whitnall (phd)
Publications:

Cancer Therapeutics and Targeting

Primary supervisor: Patric Jansson

Overcoming drug resistance is crucial for development of new effective therapeutics for cancer treatment. Multidrug resistance (MDR) is a phenomenon in which cancer cells are resistant to the cytotoxic effects of various chemotherapeutic agents. One major mechanism by which this occurs is through the over-expression of ATP-dependent drug efflux transporters such as the P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP).

Many human tumours show pronounced hypoxia and extracellular acidosis. In vitro, this acidic environment has a strong impact on the activity of Pgp drug transporter responsible for multidrug resistance. The hypoxia-inducible factor (HIF)-1 is a master transcriptional activator of oxygen-regulated genes and HIF-1 is constitutively up regulated in several tumour types under hypoxic conditions and HIF-1 might thus be implicated in tumour therapy resistance.

We have developed agents that can bind iron and activate HIF-1 by iron depletion. They have been proved to exert selective anti-tumour activity in vitro and in vivo and also overcome resistance to standard chemotherapeutics.  Considering the marked therapeutic potential of these agents, this Honours’ project will investigate whether iron chelation, HIF-1 activation, hypoxia and Pgp is important for how these novel agents overcome drug resistance.

This project will use a combination of cutting-edge techniques including: cell culture, western blotting, siRNA, cytotoxicity detection and fluorescent/confocal microscopy etc.


Discipline: Pathology
Co-supervisors: Des Richardson
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