Lab Head: Nick Leslie Institute of Biological Chemistry, Biophysics and Bioengineering

Research

The class I PI 3-kinases are a family of tightly regulated lipid kinases that generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), in response to growth factors, cytokines and other intercellular mediators. Through selective interactions with diverse downstream targets such as the AKT protein kinases, PIP3 is able to contribute to the regulation of the growth, motility, survival and metabolic responses of many cell types to a wide variety of hormonal and environmental cues.

PIP3 can be metabolised by two groups of phosphatases, 3-phosphatases such as the tumour suppressor, PTEN, or 5-phosphatases such as SHIP and SHIP2. Our current work focuses largely on these phosphatases, PTEN and SHIP2, and how their regulation and activities contribute to the outcomes of PI3K signalling.

  1. PTEN regulation
    • We are studying the regulation of PTEN by phosphorylation, oxidation and ubiquitination
  2. PTEN's mechanisms of action
    • In addition to its PIP3 lipid phosphatase activity, PTEN also has protein phosphatase activity and we are attempting to determine the significance of this activity. We are also studying the mechanisms by which loss of PTEN drives tumour formation independently of the AKT kinases.