New Jackson Laboratory Researcher Investigates Cell Growth and Cancer
JAX® NOTES Issue 506, Summer 2007
All of us harbor proto-oncogenes, genes which, when functioning properly, orchestrate development and growth with astonishing precision but, when malfunctioning, can cause cancer. Proto-oncogenes are the study subject of Casey Fox PhD, a new associate staff scientist at The Jackson Laboratory. Specifically, Dr. Fox studies a proto-oncogene family called the proviral insertion site (PIM) kinases. Kinases, of which about 520 are known in humans, are proteins that regulate how a cell responds to its environment. Kinase-encoding genes represent a large fraction of proto-oncogenes. PIM family members Pim1 through Pim3 were first cloned in the early 1980s and have since been implicated in many cancers, including leukemia and prostate cancer. However, their functions are just starting to be known.
PIM kinases 1, 2, and 3 are known to work together. Whereas animals missing any one of these are viable and appear quite normal, animals missing all three are about 30% smaller and have 30% fewer cells than normal throughout all systems, indicating that the PIM kinases regulate cell division and growth in all tissues. Dr. Fox says: "They're different from other kinases and seem to fill an important niche in the control of cell growth that we are just beginning to understand. Their function is regulated differently. Understanding how the PIM kinases work is key to unlocking their therapeutic potential in patients."
Dr. Fox is also researching the potential role of PIM kinases in immune response. He discovered that the immune system of mice lacking Pim1 and Pim2 fails to generate a proper response to pathogens. Careful targeting of the Pim1 and Pim2 kinases during and after organ transplants, or as part of autoimmune disease therapy, may help suppress the immune response and minimize tissue rejection while keeping all other cells and systems intact.
Dr. Fox obtained his BS in 1993 from Trinity College, University of Toronto, and his PhD in 1999 from the Department of Immunology, University of Toronto. He was a post-doctoral fellow at Abramson Family Cancer Research Institute, Philadelphia, PA from 1999-2005. Dr. Fox brings unique expertise and provides additional breadth of knowledge to our cancer research program.
Selected References
Adam M, Pogacic V, Bendit M, Chappuis R, Nawijn MC, Duyster J, Fox CJ, Thompson CB, Cools J, Schwaller J. 2006. Targeting PIM kinases impairs survival of hematopoietic cells transformed by kinase inhibitor-sensitive and kinase inhibitor-resistant forms of Fms-like tyrosine kinase 3 and BCR/ABL. Cancer Res 66:3828-35.
Fox CJ, Hammerman P, Thompson CB. 2005. Fuel feeds function: energy metabolism and the T cell response. Nat Rev Immunol 5:844-52.
Fox CJ, Hammerman P, Thompson CB. 2005. The Pim kinases control rapamycin-resistant T cell survival and activation. J Exp Med 201:259-66.
