Dr. Robert G. Korneluk is a Member of the Order of Canada (C.M.) and a professor in the Departments of Pediatrics and Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa. He is also a Senior Scientist and the Scientific Director of the Apoptosis Research Centre at the Children’s Hospital of Eastern Ontario Research Institute and a Distinguished Professor of the University of Ottawa. He is a Fellow of the Royal Society of Canada and has received the prestigious McLaughlin Medal from the Society. He was an International Research Scholar of the Howard Hughes Medical Institute for three 5-year terms (1997-2012). His laboratory studies fundamental aspects of apoptosis, an intrinsic mechanism by which a cell initiates a genetic process to commit programmed cell death.
Dr. Korneluk’s group identified, in 1995, the mammalian inhibitor of apoptosis (IAP) genes, cIAP1, cIAP2, XIAP and NAIP. Since then, they have studied the role of the IAPs in normal cell function (immunity, neurobiology and myogenesis) and in disease (cancer, auto-immunity, AIDS, retinal eye disease, neurodegeneration, muscular dystrophy and skeletal muscle atrophy). Also, in the past several years Dr. Korneluk has been investigating the mechanism of action of a class of IAP antagonists, called Smac mimetics, which are small molecule compounds that potently degrade cIAP1, cIAP2 and XIAP, and which are in the clinic for the treatment of cancer. Dr. Korneluk’s current translational research program continues to investigate the utility of these small molecule drugs and their proteolysis targeting chimera (PROTAC) derivatives for the treatment of cancer and other diseases
Targeted Ablation of the Cellular Inhibitor of Apoptosis 1 (cIAP1) Attenuates Denervation-Induced Skeletal Muscle Atrophy
Skeletal muscle atrophy is a pathological condition that contributes to morbidity in a variety of conditions including denervation, cachexia, and aging. These results demonstrate the cIAP1 is an important mediator of NF-κB/MuRF1 signaling in skeletal muscle atrophy and is a promising therapeutic target for muscle wasting diseases.
The Transcription Factor SP3 Drives TNF-α Expression in Response to Smac Mimetics
The controlled production and downstream signaling of the inflammatory cytokine tumor necrosis factor-α (TNF-α) are important for immunity and its anticancer effects.
Smac Mimetics Synergize With Immune Checkpoint Inhibitors to Promote Tumour Immunity Against Glioblastoma
Overall, this combinatorial approach could be highly effective in clinical application as it allows for cooperative and complimentary mechanisms in the immune cell-mediated death of cancer cells.
Smac Mimetics and Innate Immune Stimuli Synergize to Promote Tumor Death
As these and other adjuvants have been proven safe in clinical trials, it may be worthwhile to explore their clinical efficacy in combination with SMCs.