Continued


Validation of genes modulated by RASSF1A following DSS induced colitis in mice.


Student: Celine Zhou Supervisor: Dr. Shairaz Baksh, University of Alberta


Similar to the work described on page 10, this work is focused on how the body uses and controls inflammation so that it is beneficial, and not harmful.


Our immune system has developed several intricate mechanisms to protect us from external insults. Inflammation is a key defense mechanism that triggers tissue healing and wound repair. Although this process is typically well- regulated, chronic inflammation may pose serious risks to the well-being of an individual and increase the likelihood of diseases such as IBD. On a molecular level, persistent inflammation may occur because of overproduction of cytokines


and chemokines, chemicals that favor inflammation. A lot is known about what activates this overproduction, but not much has been published on what will shut it down.


IBD has been recently genetically linked to a protein known as “Ras-association domain family protein 1A,” or RASSF1A. RASSF1A is able to regulate cell death (important in control of inflammation) mediated by tumor necrosis factor alpha receptor, or TNF-α (as we know, infliximab and adalimumab are biological drugs that work by blocking TNF) and another protein, named modulator of apoptosis (MOAP-1). These researchers speculate that there may be loss of function of RASSF1A in many IBD patients. In standard models of IBD, preliminary studies demonstrated that mice lacking either RASSF1A or MOAP- 1 become quite ill compared to mice having these proteins. Thus, it appears that these two proteins may function to suppress excessive inflammation. In a standard colitis model, the studies


also showed that survival rates of mice lacking either RASSF1A or MOAP- 1 were better in a controlled (clean) environment, when compared to the same mice in a “dirtier” environment.


This work then went on to explore the effect of resveratrol, a plant-based anti- oxidant. Double-knockout mice (mice lacking both RASSF1A and MOAP-1) were fed resveratrol for five weeks prior to being given colitis, to determine its effects on the ability of intestinal lining cells to recover from induced damage. Although mice fed resveratrol did better than controls, the female mice developed blood clots and had multiple disease symptoms leading to death within days, while the males tended to recover. This interesting observation needs further study.


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EDITION 3 | 2011 The Journal 11


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