Karl Riabowol, PhD, University of Calgary

The Riabowol laboratory studies the mechanisms 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. They examine the roles of tumour suppressors, telomeres and transcription factors in these processes. Several years ago they discovered a novel tumour suppressor they 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. Their ongoing research program focuses upon determining how they 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. They also hope to help define how mutation of the lamin A gene and its association with ING proteins causes HGPS accelerated aging in children.