Mojgan Djavaheri-Mergny received her PhD in pharmacology from the University of Paris XI in 1993. After a post-doc in Daniel Scherman‘s laboratory, she obtained an INSERM research position in 1996.
She then worked in the INSERM units run by Louis Dubertret at the Saint-Louis Hospital in Paris, Jeanne Wietzerbin at the Curie Institute in Paris, and Patrice Codogno at the University of Paris XI, before moving in September 2009 to the INSERM unit at the Bergonié Cancer Institute where she runs a group studying the regulation of autophagy in tumours.
REGULATION OF AUTOPHAGY IN CANCER CELLS
Our current research focuses on the role of autophagy in tumour responses to therapy. Autophagy, a lysosomal process used by the cell to degrade and recycle cytoplasmic constituents, is essential for cell survival, differentiation and the maintenance of cellular homeostasis. It is positively regulated by several tumour suppressor genes. Defective autophagy is associated with increased tumorigenesis and its inhibition often sensitizes cancer cells to anti-tumour therapies. Our goal is to better understand the links between autophagy and cell death pathways in tumours. Our previous studies provided evidence in favour of the regulation autophagy by apoptosis-regulatory factors. Indeed, we demonstrated that activation of NF-kappaB (which inhibits apoptosis) mediates the repression of autophagy in cancer cell lines. On the other hand, we have provided evidence for the regulation of autophagy by p53, a pro-apoptotic transcription factor that is frequently deregulated in cancer cells. We also found that Beclin 1 (which is a key protein involved in the initiation of autophagy) is cleaved by caspases during apoptosis. Moreover, we have recently explored the regulation of the autophagy pathway during the differentiation of leukemia cells.
THE OBJECTIVES OF OUR PROJECT ARE:
i) to identify the molecular events through which apoptosis and autophagy regulate each other.
ii) to explore the regulation and functions of autophagy-regulatory proteins (Atg proteins)
iii) to identify and explain correlations between the regulation of autophagy and chemoresistance in tumours and cell lines in the Institut Bergonié tumour bank.
Understanding the regulation of autophagy should yield important clues about autophagy’s role in chemoresistance and oncogenesis. We expect this work to lead to the development of new therapeutic approaches that may help in the treatment of cancer.
Trocoli A, Mathieu J, Priault M, Reiffers J, Souquere S, Pierron G, Besançon F and Djavaheri-Mergny M. ATRA-induced upregulation of Beclin 1 prolongs the life span of mature Acute Promyelocytic Leukemia cells Autophagy. 2011 7:1-7.
Trocoli A and Djavaheri-Mergny M. The complex interplay between autophagy and NF-kappaB signalling pathways in cancer cells. Am. J. Cancer Res. 2011 1:629-649.
Djavaheri-Mergny M, Maiuri MC and Kroemer G. (2010) Cross talk between apoptosis and autophagy by caspase-mediated cleavage of Beclin 1.Oncogene 29, 1717-9.
Lorin, S., Borges, A., Ribeiro Dos Santos, L., Souquere, S., Pierron, G., Ryan, K. M., Codogno, P., & Djavaheri-Mergny, M. (2009). c-Jun NH2-terminal kinase activation is essential for DRAM-dependent induction of autophagy and apoptosis in 2-methoxyestradiol-treated Ewing sarcoma cells. Cancer Research 69, 6924-693.
Tasdemir, E., Maiuri, MC., Galluzzi, L., Vitale, I., Djavaheri-Mergny, M., D’Amelio, M., Criollo, A., Morselli, E., Zhu, C., Harper, F., Nannmark, U., Samara, C., Pinton, P., Vicencio, JM., Carnuccio, R., Moll UM, Madeo, F., Paterlini-Brechot, P., Rizzuto, R., Szabadkai, G., Pierron, G., Blomgren, K., Tavernarakis, N., Codogno, P., Cecconi, F. et Kroemer G. (2008) Regulation of autophagy by cytoplasmic p53. Nature Cell. Biol. 10, 676-87.
Djavaheri-Mergny, M., Amelotti,M., Besançon, F., Bauvy, C., Codogno, P. (2007) Regulation of autophagy by NF-kappaB transcription factor and reactive oxygen species. Autophagy. 3, 390-2.
Djavaheri-Mergny, M., Amelotti, M., Mathieu, J., Besancon, F., Bauvy, C., Souquere, S., Pierron, G., & Codogno, P. (2006) NF-kappaB activation represses tumor necrosis factor-alpha-induced autophagy. The Journal of Biological Chemistry 281, 30373-30382.