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Dr. Gallouzi鈥檚 research is on novel ways to trigger the death of cancer cells and to prevent cancer-induced muscle wasting (cachexia):

1)听听听 Mechanisms of action of the protein HuR in cell growth and cell death听- Cancer progression and development results from deregulated, excessive growth and resistance to death. One focus of our group is to study HuR, a protein involved in both cell growth and cell death. Importantly, excessive growth in cancer has been linked partly to an abundance of HuR. We have shown however that HuR also is prominent in mediating the death of cells exposed to certain detrimental conditions (Mazroui et al., 2008), when HuR encourages cell death instead of survival. Furthermore, we have discovered that when cells are exposed to certain anti-cancer drugs, HuR protein is cut in two (Mazroui et al., 2008; von Roretz and Gallouzi, 2010), resulting in a switch from promoting survival to promoting death; the 鈥渃leavage products鈥� remain in the cell each performing their respective activities.

2)听听听 HuR cleavage and its putative role in resistance to chemotherapy -听We have seen that when cancer cells become resistant to chemotherapeutics, HuR cleavage is impaired. In breast cancer cells resistant to anti-cancer chemotherapeutics, where HuR is not cleaved, our experiments have indicated that treating these cells with the two cleavage products of HuR promotes their death by chemotherapeutics to which they were otherwise resistant. Before testing these peptides in humans, we are using a mouse model of breast cancer to confirm that the cleavage products induce cell death in tumor cells. Determining how HuR and its cleavage products induce cell death will hopefully aid us to discover new therapeutic targets for this devastating disease.

3)听听听 The potential of chemical compounds that impair protein production as drugs for cachexia and tumor growth听- Cachexia is a debilitating syndrome characterized by a rapid loss of muscle mass in diseases such as cancer, AIDS or chronic infections. The fact is that ~ 50% of all cancer deaths is due to consequences (lower quality of life, decreased response to chemotherapy) associated with this condition, but to date no treatment has proven effective. Recently, we demonstrated that low doses of chemical compounds that interfere with protein production inside the cell are able to prevent cancer-induced muscle wasting, and to block tumor growth. We demonstrated the effectiveness of these drugs in blocking the expression of factors that promote cachexia (Di Marco et al., 2005) in vitro (cell model) in vivo (mouse model for cachexia) (Di Marco et al., under revision). In collaboration with both basics scientists (GCRC, Drs. J. Pelletier and M. Tremblay) and clinicians (Jewish Hospital, Drs. N. McDonald) we intend to test these compounds in a clinical setting.

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