Office Phone: 514-252-3400 ext. 4684
Lab Phone: 514-252-3400 ext. 3349
Research Axis Immunology-Oncology
Research Unit Cellular Response to Anticancer Agents
- Full Professor
DISTINCTIONS AND ACHIEVEMENTS
NCIC Career Scientist Award
Senior Investigator Award, FRSQ
- Xiaoming Yang, Technician
- Tara Harihar, Technician
- Mustapha Aouida, Postdoctorate
- Karima El Fadili, Postdoctorate
- Jim Daley, Postdoctorate
- Nathalie Jouvet, Ph.D.
- Jeremie Poschmann, Ph.D.
- Ali Khodami-Pour, Ph.D.
- Chadi Zakaria, Ph.D.
- Siham Berra, M.Sc.
- Emily Ayoub, M.Sc.
- Sami Hsine (intern)
- Rim Marrakchi, visiting student from Tunisia
There are three funded projects in my laboratory
- Project I (CIHR): To investigate the mechanism by which cells develop resistance to the antitumor drug bleomycin. Using yeast as a model system, we established by a genome-wide approach that there are five genes that when deleted cause > 1000-3000-fold resistance to bleomycin. We showed that one of these genes, AGP2, encode a transporter of bleomycin. Deletion of AGP2 blocked the uptake of bleomycin into the cell and caused remarkably resistance to the drug. More importantly, we established that Agp2 is the long sought high affinity transporter of polyamines, which transports polyamines as well as polyamine-conjugated drugs, e.g., bleomycin, into the cell. We are in the process of showing that the human CT2 transporter performs a similar function as the Agp2 transporter. hCT2 is highly expressed in testicular cells and might explain the high cure rate of testicular cancer by bleomycin. Individuals defective in hCT2 function are expected to be resistant to bleomycin.
- Project II (CIHR): To investigate the role of the phosphatase activator PTPA1 in response to stress. Briefly, we recently showed that rapamycin triggers the degradation of RNA polymerase II in a PTPA1 dependent manner. We now have direct evidence that PTPA1 interacts with RNA pol II and isomerizes the CTD to trigger the enzyme release from the chromatin in cells treated either with DNA damaging agents or rapamycin. In the absence of PTPA1, RNA pol II remains bound to the chromatin.
- Project III (NSERC): To investigate the role of AP endonucleases in processing oxidative DNA lesions. Briefly, we have established that Apn1 has multiple activities including the ability to directly remove oxidized lesions in the genome. More recently, we found that Apn1 may play an important role in processing these lesions during specific phase of the cell cycle.
Vongsamphanh, R., Fortier, P-K., and Ramotar, D. (2001) Pir1p mediates translocation of the yeast Apn1p endonuclease into the mitochondria to maintain genomic stability. Mol. Cell. Biol. 21:1647-1655.
Karumbati, A.S., Deshpande,R. A., Jilani, A., Vance, J.R., Ramotar, D., and Wilson, T.E. (2003). The role of yeast DNA 3’ phosphatase Tpp1 and Rad1/Rad10 endonuclease in processing spontaneous and induced base lesions. J. Biol. Chem., 278:31434-31443.
Aouida, M., Pagé, N., Leduc, A., Peter, M., and Ramotar, D. (2004) A genome-wide screen in Saccharomyces cerevisiae reveals altered transport as a mechanism of resistance to the anticancer drug bleomycin. Cancer Res., 64: 1102-1109.
Andrea Shatilla, Anick Leduc, Xiaoming Yang, and Dindial Ramotar. (2005) Identification of two apurinic/apyrimidinic endonucleases from Caenorhabditis elegans by cross species complementation. DNA repair (Amst)., 4:655-670.
Aouida, M., Leduc, A., Poulin, R., and Ramotar, D. (2005) Agp2 encodes the major permease for high affinity polyamine import in Saccharomyces cerevisiae. J. Biol. Chem., 280:24267-24276.
Alexander A. Ishchenko, Xiaoming Yang, Dindial Ramotar, and Murat Saparbaev. (2005) The 3’→5’ exonuclease of Apn1 provides an alternative pathway to repair 7,8-dihydro-8-oxodeoxyguanosine in Saccharomyces cerevisiae. Mol. Cell. Biol. 25, 6380-6390.
Vongsamphanh, R., Wagner, R. J., Ramotar, D. (2006) Saccharomyces cerevisiae Ogg1 prevents poly(GT) tract instability in the mitochondrial genome. DNA Repair (Amst). 2006 Feb 3;5(2):235-42. Epub 2005 Nov 15.
Douville, J., David, J., Lemieux, K. M., Gaudreau, L., Ramotar, D. (2006) The Saccharomyces cerevisiae phosphatase activator Rrd1 is required to modulate gene expression in response to rapamycin exposure. Genetics, Feb;172(2):1369-72 (Epub 2005 Dec 1).
Aouida, M and Ramotar, D (2006). Bleomycin holds the key for improved anticancer therapy. Cancer Therapy, 4: 171-182.
Azam, S., Drobetsky, E., and Ramotar, D. (2007) Overexpression of the cis/trans isomerase PTPA triggers caspase 3-dependent apoptosis. Apoptosis, 2007 Feb 27; [Epub ahead of print].