RPP Profile: Dr. Jim Davie

Dr. Jim Davie is an incredible asset to the Canadian health research community and to CIHR. He is the current Executive Director of the Manitoba Health Research Council (one of CIHR's partners), he has served as a member and Chair on CIHR's peer review committees, and he is a Canada Research Chair (Tier 1) in Chromatin Dynamics. Dr. Davie has published over 165 papers, which have been highly cited. In 2004, his citation record was identified as being in the top one per cent of all biology and biochemistry scientists in the past 10 years.

Among the multiple grants and salary awards that Dr. Davie has received throughout his research career, the funding he received through CIHR's Regional Partnerships Program* (RPP) stands out in his mind. "The RPP supported a component of my research program that allowed me to retain my highly skilled staff and continue our project in cancer biology," he recalls. "I would have run into a big problem with one of my projects without the RPP support and I wouldn't have been as competitive for the Canada Research Chair. There's no doubt in my mind."

The project itself had already received funding through the National Cancer Institute of Canada (NCIC), but the grant was coming up for renewal. Dr. Davie, however, happened to be the Chair of the appropriate peer review committee with the NCIC, so he decided to send his application to a different committee. "Strategically," he chuckles, "that may have been a mistake."

Dr. Davie submitted his application to both CIHR and to the NCIC. While the application scored in the fundable range at both organizations, the scores were not high enough to bring the application beyond either organization's financial cut-off point. RPP is designed to catch those hidden gems that fall just below that cut-off point in CIHR's open competitions**, and the program provided Dr. Davie with interim support to maintain and grow his research project. The support he received through RPP enabled his research team to collect the "all-important preliminary data" that led to a strengthened – and highly competitive – operating grant application in the following NCIC competition.

The RPP funding supported Dr. Davie's research on tumorigenesis, which is a progression of events resulting from alterations in genetic information and in the ways genes are turned on and off. Modifications of DNA and histones (which act as spools for DNA to wind around) alter gene activity and are referred to as "epigenetic processes." These processes are potentially reversible events that modify gene function without changing the DNA sequence. For example, think of a paragraph of print on a regular sheet of paper. Now imagine that piece of paper folded over and over like an accordion. If you open the folded sheet up, you can see that the folding doesn't alter the words or letters on the page, but if you keep one part of the "accordion" folded, the folding will change the way you read the original paragraph. Epigenetic processes are natural and essential to many organism functions, but if they occur improperly, major adverse health effects – including cancer – can ensue.

"We have a hope of fighting cancer when the epigenetic events are reversible," he explains.

The RPP funding also supported the salaries of one lab technician and one graduate student, but Dr. Davie notes that many of his graduate students get funding support through their own awards. In particular, he fondly describes the "dynamic duo" in his lab: a post-doctoral fellow and a Ph D candidate. "They played off of each other and ended up being more productive by encouraging one another," he recalls. "They were always getting better, but [the duo] may never have happened without the RPP support for the rest of the project."

The external support for his graduate students allowed Dr. Davie to use more of the grant funds for operating expenses, which can get fairly high. "Experiments are expensive," he says. "For example, we may do experiments with antibodies. Before we start the experiments, we try samples of antibodies from three or four different companies to ensure that we get the best possible material for our work. We have to pay for those samples, of course, and when we find the best one, we order a large quantity of it. We can use 20-30 different antibodies, too – and we need samples and large quantities of all of them."

With the support of RPP, Dr. Davie and his team were able to collect the "best data in a long time." In fact, the data from the RPP-funded project is being applied to Dr. Davie's breast cancer research, too. "We're starting to see more women in their thirties diagnosed with more aggressive, estrogen-receptor negative cancers, which is a disturbing trend," he explains.

Estrogen-receptor positive breast cancers generally have a better prognosis and are often responsive to anti-estrogen treatments. Estrogen-receptor negative breast cancers, however, are not responsive to anti-estrogen treatments and require new, targeted therapies. Dr. Davie has a project funded by the Canadian Breast Cancer Foundation to determine the role of a peroxiredoxin (which is a type of antioxidant enzyme that regulates hydrogen peroxide levels in the cell) in regulating gene expression and metastasis. Peroxiredoxins are over-expressed in breast cancer, and Dr. Davie previously discovered that one in particular, NKEF-A, is associated with the DNA of some highly malignant breast cancer cells. The DNA associated with NKEF-A will be sequenced to identify the genes regulated by the peroxiredoxin, and Dr. Davie and his team will investigate how nuclear expression of NKEF-A – or having the gene to produce NKEF-A turned "on" – correlates with breast cancer aggressiveness.

"The foundation for this research was rooted in the RPP project," he notes.

The RPP funding supported an important component of an incredibly successful research career. Among all his accolades, though, the recognition that Dr. Davie cherishes most is the University of Manitoba Health Science's Graduate Students' Association Award for Distinction in Mentorship (2006). He acknowledges that the talent of his trainees and research staff has been the major reason for his research success.

*CIHR's Regional Partnerships Program (RPP) is designed to build research capacity in Saskatchewan, Manitoba, New Brunswick, Nova Scotia, Newfoundland and PEI, and to maintain the health research excellence that already exists in these regions.

**Applicants from participating RPP regions are not automatically considered for RPP support. For more information, please visit the Contact Information webpage.