CMRC Children's Memorial Research Center
Abdelhadi Rebbaa

Abdelhadi Rebbaa

Children's Memorial Research Center
2300 Children's Plaza, Box 224
Chicago, IL 60614
Phone: (773) 755-6532
Fax: (773) 755-6518

Year Degree Institution
1993 Ph.D. in Biochemistry Claude Bernard University, Lyon, France.

Research Interests
Research in my laboratory addresses the phenomenon of drug resistance in cancer from two unique angles:
One of the projects aims to study the contribution of tumor cell environment to cellular adaptation to cytotoxic stress and amplification of resistance to chemotherapy. Drug resistant tumors contain not only cells that have acquired the drug resistant phenotype, but also other supporting cells such as fibroblasts and endothelial cells necessary for survival of the tumor as a whole. However, the mechanism by which these supporting cells survive drug toxicity has not been addressed. We made the hypothesis that cancer cells that have acquired the resistance phenotype may send survival signals to neighboring drug sensitive cells so they can escape drug toxicity. By using drug resistant and sensitive neuroblastoma cell as a model, we have found that the resistant ones secrete a survival molecule named midkine, able to protect drug sensitive cells from doxorubicin-induced cell death. The action of midkine was found to depend on inhibition of apoptosis through activation of the survival pathway mediated by Akt. Further studies in this project are directed towards dissecting the signaling pathways that mediate midkine cytoprotective action from the plasma membrane to the nucleus. This project is funded by grant from the NCI (# 1R01 CA096616-01A1 to A.R).
The second area of research in my lab is directed towards defining the earliest events that dictate cancer cells to undergo proliferation arrest, cell death, or to adapt to drug toxicity and become drug resistant. Initial work in our laboratory led to the finding that inhibition of apoptosis alone was not sufficient for cancer cells to become drug resistant. An earlier toxic response leading to irreversible growth arrest (also called senescence) appeared however to play a key role in the onset of drug resistance as well as in its reversal. We have found that forcing drug resistant cells to undergo senescence alone was sufficient not only to reverse but also to prevent development of drug resistance. Based on these findings, our focus is currently directed towards further understanding of the mechanism by which cancer drugs induce cellular senescence and identification of new ways to target this cellular demise in order to enhance cancer chemotherapy efficacy.

Last Updated: May 2 2006 9:53AM

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