The major goals of my research program are to understand the molecular basis of cell-cell and cell-extracellular matrix interactions in normal and pathological conditions. A specific objective is to understand the cross-talk between signal transduction pathways induced by cell adhesion and growth factors, cytokines and chemokines. An understanding of the integration of these pathways should allow for the identification of molecular targets in the control of complex diseases such as cancer, kidney and cardiovascular diseases and arthritis.

One major focus of my research program is Integrin-Linked Kinase (ILK), which integrates Integrin signal transduction with growth factor signaling in the context of regulating cellular cytoskeletal architecture. ILK performs as a signaling node by forming a multiprotein complex to regulate flux through various signaling pathways which regulate vital cellular processes such as cell survival and apoptosis, cell proliferation, and cell migration and motility. We are using tissue-specific knock out strategies to understand the role of ILK the development and function of different tissues and organs. To date we have uncovered an essential role of ILK in embryonic blood vessel formation and tumour angiogenesis, as well in the development of the brain and long bones. We are also using transgenic mice to understand the role of ILK in cancer progression and cardiovascular function.

ILK expression and activity are significantly increased in cancer versus normal tissue, and ILK promotes cancer formation and progression to metastasis in experimental model systems. We have developed highly selective inhibitors of ILK function, and these compounds inhibit tumour growth without effecting normal cells. Preclinical experiments show that these compounds will be useful as anticancer therapeutics and clinical trials should begin in the near future.

A second major focus of my research program is the development of experimental models to study cancer metastasis. We are developing mouse and 3-dimensional cell models to identify the molecular basis of cancer metastasis formation and specifically, the growth of metastatic cells in different organs. We are combining genetic, proteomic and live imaging technologies to identify genes and proteins that promote cancer metastasis. These models will also be used for the testing of novel and existing therapeutics for the treatment and control of cancer metastatic growth.