Dr. Russell Jones
Rosalind and Morris Goodman Cancer Research Centre
Department of Physiology
1. CIHR New Investigator Award
2. William Dawson Scholar, McGill University, 2014
3. Dr. Ann Wechsler Award for Excellence in the Teaching of Physiology, U3, McGill University, 2014
4. Bernard and Francine Dorval Prize, The Canadian Cancer Society, 2014
Dr. Jones’ laboratory is interested in studying the molecular mechanisms underlying cellular growth and proliferation, and how these processes are normally regulated in the immune system or deregulated during tumourigenesis.
The ability of a cell to successfully grow and divide depends on the cell having enough energy to complete the task. Cancer is essentially a disease in which cells lose the normal checks and balances that prevent them from growing out of control. However, part of the challenge that faces cancer cells is that they require increased amounts of fuel and energy to meet the demands of uncontrolled growth. To meet this challenge, cancer cells often display fundamental changes in energy generation, or metabolism. Part of the metabolic shift seen in cancer cells is their increased dependence on sugars for energy production, a phenomenon known as the “Warburg Effect”. This phenomenon is the principle behind PET scans used in the clinic, which image tumours based upon their increased ability to take up sugar.
Research in the laboratory centers on two main areas:
1) Understanding of the critical interactions between signal transduction pathways and cellular metabolism. Of particular interest is the function of the AMP-activated protein kinase (AMPK), a critical regulator of cellular metabolism. Dr. Jones’ team has recently found that AMPK is a key regulator of cell survival in response to a number of metabolic stresses. They previously demonstrated that AMPK interacts with the tumour suppressor p53 to promote cellular adaptation to metabolic stress. Using a variety of tools including biochemistry, metabolic analysis, cell biology, bioinformatics, and mouse models, they have been investigating how AMPK regulates p53 function, and how metabolic control of p53 affects cellular metabolism and tumourigenesis. The hope is that by understanding the metabolic networks at play in both normal and pathological settings (i.e. cancer) they may gain insight that will lead to novel therapeutics for the treatment of cancer.
2) The molecular and genetic pathways that regulate immune function, with particular emphasis on T lymphocytes. T lymphocytes, or T cells, are “sentinels” of the immune system whose function is to identify and eliminate infected cells. One of the challenges of vaccine development is the ability to generate enough “memory” T cells to mount an effective T cell response against a virus or tumour cell. Within this vein of research Dr. Jones’ team has investigated the potential role that cellular metabolism, and its control by AMPK, plays in the generation of T cell memory. They found that activating AMPK with the anti-diabetes drug metformin can enhance the formation of CD8+ T cell immunological memory in mice, and significantly improved how well an experimental vaccine could work against an aggressive tumour.
Moreover, they have found that AMPK acts to control inflammation by regulating the function of dendritic cells, cells of the innate immune system which regulate T cell activation. These studies give them hope that manipulation of T cell metabolism may lead to effective therapies for vaccination, or the control of inflammation and autoimmune disease.