Ph.D., University of Bordeaux, 1995
Office: 4009 Hixon | Lab: 4003 Wahl Hall West
913-588-7010 | email
The Human T-cell Leukemia/Lymphoma Virus Type I (HTLV-I) is a complex human retrovirus discovered in 1980 and associated with adult T-cell leukemia/lymphoma (ATLL) as well as neurological disorders known as TSP/HAM. Both diseases have their etiology in virus-induced deregulated growth of infected CD4 T-cells. The viral oncoprotein Tax plays a major role in the viral pathogenesis by interfering with cell cycle, DNA repair and apoptosis/survival pathways. Our research integrates molecular biology/biochemistry and cell biology technologies to investigate molecular mechanisms underlying Tax-mediated cellular transformation with a special emphasis on apoptosis and survival pathways hijacked by Tax. We recently demonstrated that Tax reactivates telomerase functions in T-cells and we are investigating the mechanisms involved in this process. Because telomerase activity is present in 90% of all human cancers but not in normal cells, and is require for continuous proliferation of transformed cells, it represents an advantageous target for cancer therapy. The second theme of our research resulted from our recent discovery of a new viral RNA-binding protein (p30) that prevents nucleo-cytoplasmic export of specific viral RNA and inhibits virus expression. By doing so, p30 redirects virus expression to a latent infection and facilitates the host’s immune escape. Investigations aim at understanding regulations of p30 expression and p30-viral RNA interactions.
Nicot C, Mahieux R, Takemoto S, Franchini G.: Bcl-xL is up-regulated by HTLV-I and HTLV-II in vitro and in ex vivo ATLL samples. Blood 96:275-81, 2000.
Nicot C, Harrod R: Distinct p300-Responsive Mechanisms Promote Caspase-Dependent Apoptosis by Human T-Cell Lymphotropic Virus Type 1 Tax Protein. Molecular and Cellular Biology 20:8580-89, 2000.
Mahieux R, Pise-Masison C, Gessain A, Brady JN, Olivier R, Perret E, Misteli T, and Nicot, C.: Arsenic trioxide induces apoptosis in HTLV-1 and HTLV-2 infected cells by a caspase-3 dependent mechanism involving Bcl-2 cleavage. Blood 98: 3762-3769, 2001.
Nicot C, Mahieux R, Pise-Masison C, Brady J, Gessain A, Yamaoka S, Franchini G.: HTLV-I Tax represses c-Myb-dependent transcription through activation of the NF-kappa B pathway and modulation of coactivator usage. Molecular and Cellular Biology. 21:7391-7402, 2001.
Nicot, C., Dundr, M., Jonhson, J., Fullen, J, Alonzo, N., Fukumoto, R., Princler, G.L., Derse, D.,Misteli, T., and Franchini, G.: A novel post-transcriptional negative regulator of HTLV-1 replication. Nature Medicine 10 (2):197-201, 2004.
Sinha-Datta, U., Horikawa, I., Michishita, E., Datta, A., Sigler-Nicot, J. C., Brown, M., Kazanji, M., Barrett J. C., and Nicot, C. Transcriptional activation of hTERT through the NF-kB pathway in HTLV-I transformed cells. Blood 104: 2523-2531, 2004.
Datta A, Bellon M, Sinha-Datta U, Bazarbachi A, Lepelletier Y, Canioni D, Waldmann T A, Hermine O and Nicot C. Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence. Blood 108(3):1021-9, 2006.
Brown M, Bellon M and Nicot C. Emodin and DHA potently increase arsenic trioxide interferon alpha induced cell death of HTLV-I transformed cells via generation of reactive oxygen species and inhibition of Akt and AP1. Blood. 2007 Feb 15;109(4):1653-9.
Sinha-Datta U, Datta A, Ghorbel S, Dodon MD, Nicot C. Human T-cell lymphotrophic virus type I rex and p30 interactions govern the switch between virus latency and replication. J Biol Chem. 2007 11;282(19):14608-15.
Datta A and Nicot C. Telomere Attrition Induces a DNA Double Strand Break Damage Signal that Reactivates p53 Transcription in HTLV-I Leukemic cells. Oncogene 2007 Aug 20; [Epub ahead of print]
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