Signal Transduction

Group Head: Associate Professor Pu Xia

It is now believed that most of, if not all, human diseases including cancer, diabetes and heart attack, are attributed to defects in communication between and within the cells of our bodies. By understanding the process of cell communication, (called signal transduction), diseases can be treated in a more effective and safe way.

Signal transduction is a means for cells to perceive and correctly respond to their microenvironment. It is a complex system of communication that governs basic cellular activities and coordinates cell actions enabling our bodies to function properly.

The process of signal transduction often involves multiple ordered sequences of biochemical reactions and forms the communication networks inside the cell. Research in the Signal Transduction program aims to understand how cells utilise specific proteins and lipids as unique languages to communicate between and/or within cells and how the communication is jammed, leading to diseases such as cancer and diabetes. By understanding the molecular basis of diseases, we seek to develop new therapeutic strategies for prevention and treatment of diseases that account for more than a third of all deaths in Australia.

Research focus

We aim to understand how biological signals communicate between and within cells, and how they go awry leading to the development of human diseases, including cancer, diabetes and cardiovascular disease. With a strong research background in the area of lipid signalling, especially sphingolipids, this laboratory continues to play a leading role in defining the signalling mechanisms of sphingolipids and investigating their implications in these major diseases.

Our current research projects include:

• Since our first report demonstrating a tumourigenic effect of SphK, its study has been of greater interest in cancer research. A growing body of evidence suggests that SphK plays a critical role in the development of various human cancers, such as breast, lung and prostate. We have recently found that SphK is able to promote cell growth in breast cancer, helping the cells escape from death after treatment with anti-cancer drugs. We now seek to further understand the mechanisms of how cancer cells use SphK for communication to escape death and whether blocking this signalling pathway could induce killing of cancer cells.

• Atherosclerotic cardiovascular diseases including diabetic complications are now recognised as inflammatory diseases. This recognition highlights a critical role for the endothelium which normally forms a non-thrombogenic surface and selective permeability barrier for the maintenance of normal homeostasis, in particular, the so-called anti-inflammatory phenotype of the vessel wall. In various disease states (e.g. diabetes), multiple or individual risk factors damage this phenotype resulting in dramatic changes in the functional characteristics of the endothelium, rendering it adhesive and inflamed. We have found that this process of damage is mediated by the SphK signalling pathway. We are investigating how SphK mediates vascular inflammation, especially under obese, insulin resistant and diabetic pathologies. At the completion of this project, we hope to provide a potential drug target for intervention to halt or slow down the progression of obesity or diabetes-associated cardiovascular diseases.

• Diabetes is now a serious global health problem. Currently, more than one million Australians suffer from diabetes and this number is expected to double by 2015. Dysfunction or destruction of pancreatic beta-cells caused by apoptosis, programmed cell death (cell suicide), is a common pathogenic factor for both type 1 and type 2 diabetes. Thus, attempting to protect beta-cells against death and rescue their insulin secretory function is emerging as a strategy for the management of diabetes. We aim to examine how pancreatic beta-cells communicate for their survival especially under cellular stress, such as high levels of blood sugar. We also seek to understand the interrelationship between molecular mechanisms underlying defects in beta-cell survival and insulin secretion. This study will not only reveal a novel signalling pathway in the regulation of beta-cell function and survival, but may also provide a new drug target for treatment of diabetes.