Professor, Departments of Biochemistry & Molecular Biology and Oncology
Cumming School of Medicine
HMRB 374, 3330 Hospital Drive NW
Calgary AB T2N 4N1
cancer and aging, primarily at the molecular and cellular levels, examining epigenetics and telomere biology
Primary Area of Research:
Our laboratory studies the mechanisms that are critical for enforcing the state of cellular senescence in normal human cells to determine how these mechanisms are eluded during the process of cancer cell immortalization. We examine the roles of tumour suppressors, telomeres and transcription factors in these processes. Several years ago we discovered a novel tumour suppressor we called ING1 for INhibitor of Growth that is intimately involved in cell aging, the Hutchinson-Gilford progeria syndrome (HGPS) form of childhood accelerated aging, and cell immortalization leading to cancer. The ING genes encode a family of proteins produced by alternative splicing that contain plant homeodomains (PHDs) that interact with epigenetic histone marks and a LID domain that interacts with nuclear lamin proteins that when mutated, cause HGPS. These proteins also regulate apoptosis through their ability to transduce phospholipid-mediated stress signals resulting from DNA damage and to affect the DNA repair process. The ING proteins act as epigenetic regulators through their targeting of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes that regulate chromatin structure and gene expression. Our ongoing research program focuses upon determining how we can regulate the normal activity of these tumour suppressors to block the growth of cancer cells and to extend the replicative lifespan of normal cells through epigenetic modification. We also hope to help define how mutation of the lamin A gene and its association with ING proteins causes HGPS accelerated aging in children. Work in our laboratory also includes examination of telomere biology and the role of replicative senescence in aging and age-related diseases, focusing upon aspects of chromatin remodelling and functions of the ING family of type II tumour suppressors.