Laurent Susini

Laurent Susini
Nationality	French
Fields	Oncology research; tumor reversion; TCTP
Institutions	CEPHB-Fondation Jean Dausset; Caltech; Genethon; Los Alamos National Lab; Genset; Novartis
Alma mater	Paris Diderot University

Laurent Susini (born April 18, 1965) is a French molecular biologist; his research is in the area of cancer and the genetic basis of tumor reversion.

Career

Laurent Susini started at the Centre d'Etude du Polymorphisme Humain (Fondation Jean Dausset-CEPH). He obtained his PhD in Human Genetics and Molecular Biology from University Paris VII - Denis Diderot.

He contributed to the first physical map of the Human Genome at Genethon and at Genset Corporation as a member of Daniel Cohen's team, collaborating with research teams from Caltech ^[1] and the Los Alamos National Lab.^[2]

In the Lab of Prof. Moshe Oren at the Weizmann Institute of Science, he demonstrated that SIAH1 targets NUMB (gene), a protein involved in directing cell fate choices, for ubiquitin-mediated degradation.^[3] SIAH1 is a p53-inducible gene, active in the process of cell death and tumor suppression by a mechanism consisting of ubiquitination and proteasomal degradation of specific target proteins.

Approaching cancer research with a different angle, not asking why the normal cells become malignant, but rather from the patients expectations: how do my tumor cells quit their malignant status, and thus, revert?, Laurent Susini joined Molecular Engines Laboratories (M.E.L.), a biotech company with headquarters and laboratories located in Paris (France), in 2000, to develop a new generation of innovative drugs against cancer with Adam Telerman and Robert Amson.

By conducting differential gene expression and bio-informatics analyses on the tumor reversion cellular models, they identified more than 200 genes involved in the process of tumor reversion, and specifically TCTP (Translationally Controlled Tumor Protein / Translationally Controlled Tumour Protein ). This work led to potential drugs preventing, and managing cancer by inhibiting the expression of the gene tpt1/TCTP.

Laurent Susini moved to Oncology Clinical Research in 2007 to contribute in clinical early development of anti-cancer drugs. First with Quintiles and then joining the Translational Clinical Oncology department from the Novartis Institutes for BioMedical Research to design and conduct phase I clinical trials, mainly in melanoma and heme malignancies.

Research

Laurent Susini has played a critical role in the research of M.E.L founded by Adam Telerman and Robert Amson. More particularly his expertise was instrumental for the genetic and epigenetic analyses of single revertant cells from different cancer cell lines, for the identification of a "drugable" target and for the generation of pharmacological compounds able to kill cancer cells.

TCTP (Translationally Controlled Tumor Protein was identified in a screen between tumor cells and revertant cells. Inhibition of TCTP influences reversion of tumor cells. Therefore, the objective was to develop drugs targeting TCTP in cancers overexpressing the protein.

Translationally Controlled Tumor Protein (TCTP/tpt1) is a regulator of the tumor reversion program,^[4][5] tumor progression and certain forms of inflammatory diseases.^[6] Laurent Susini described TCTP as a pro-survival protein antagonizing BAX, Bcl-2-associated X protein, function ^[7]

Publications

• Susini L, Besse S, Duflaut D, Lespagnol A, Beekman C, Fiucci G, Atkinson AR, Busso D, Poussin P, Marine JC, Martinou JC, Cavarelli J, Moras D, Amson R, Telerman A. TCTP protects from apoptotic cell death by antagonizing bax function. Cell Death Differ. 2008 Aug;15(8):1211-20
• Marcel Tuynder, Giusy Fiucci, Sylvie Prieur, Alexandra Lespagnol, Anne Géant, Séverine Beaucourt, Dominique Duflaut, Stéphanie Besse, Laurent Susini, Jean Cavarelli, Dino Moras, Robert Amson, and Adam Telerman. Translationally controlled tumor protein is a target of tumor reversion. Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15364-9. (Cell Biology)
• Fiucci G, Beaucourt S, Duflaut D, Lespagnol A, Stumptner-Cuvelette P, Geant A, Buchwalter G, Tuynder M, Susini L, Lassalle JM, Wasylyk C, Wasylyk B, Oren M, Amson R, Telerman A. Siah-1b is a direct transcriptional target of p53: Identification of the functional p53 responsive element in the siah-1b promoter. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3510-5
• Fiucci G, Lespagnol A, Stumptner-Cuvelette P, Beaucourt S, Duflaut D, Susini L, Amson R, Telerman A. Genomic organization and expression of mouse Tpt1 gene" Genomics 2003 Jun;81(6):570-8
• Passer BJ, Nancy-Portebois V, Amzallag N, Prieur S, Cans C, Roborel De Climens A, Fiucci G, Bouvard V, Tuynder M, Susini L, Morchoisne S, Crible V, Lespagnol A, Dausset J, Oren M, Amson R, Telerman A (Mar 2003). "The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase". Proc Natl Acad Sci U S A. 100 (5): 2284–2289. doi:10.1073/pnas.0530298100. PMC 151332. PMID 12606722.
• Susini L, Tuynder M, Prieur S, Besse S, Fiucci G, Amson R, Telerman A (Nov 2002). "Biological models and genes of tumor reversion: Cellular reprogramming through tpt1/TCTP and SIAH-1". Proc Natl Acad Sci U S A. 99 (23): 14976–81.
• Susini L, Passer BJ, Amzallag-Elbaz N, Juven-Gershon T, Prieur S, Privat N, Tuynder M, Gendron MC, Israel A, Amson R, Oren M, Telerman A (Dec 2001). "Siah-1 binds and regulates the function of Numb". Proc Natl Acad Sci U S A. 98 (26): 15067–72.
• Amson R. B.; Nemani M.; Roperch J. P.; Israeli D.; Bougueleret L.; Linares-Cruz G.; Lethrosne F.; Pasturaud P.; Piouffre L.; Susini L.; Millasseau P.; Guidicelli C.; Bui H.; Massart C.; Cazes L.; Dufour F.; Bruzzoni-Giovanelli H.; Owadi H.; Hennion C.; Charpak G.; Dausset J.; Calvo F.; Oren M.; Cohen D.; Telerman A. (1996). "Isolation of ten differentially expressed cDNAs in p53 induced apoptosis: Activation of the vertebrate homologue of the Drosophila seven in absentia gene". Proc. Natl. Acad. Sci. USA. 93: 3953–3957. doi:10.1073/pnas.93.9.3953.
• Susini L, Ambrose WP, Jett JH, Keller RA. DNA fragment length determinations in minutes of measurement time with 2% accuracy. Patent.
• Susini L., Billault A. Les nouveaux vecteurs de clonage. Technoscope, Biofutur n°153, Février 1996
• Sambucy JL, Susini L, Gervy P, Glibert F, Beaufils S, Bui H, Massart C, De Tand Le Paslier D, Cohen D (1995). "A YAC contig map of the human genome. Sur une nouvelle technique d'analyse du caryotype humain". C R Acad Sci. 272: 2638–2640.
• Chumakov, I.M., Rigault, P., Le Gall, I., Bellanne-Chantelot, C., Billault, A., Soularue, P., Belova, M., Sambucy, J-L., Susini, L., Dib, C., Faure, S., Fizames, C., Gyapay, G., Millasseau, P., Nguyen, S., Muselet, D., Vignal, A., Morissette, J., Menninger, J., Lieman, J., Desai, T., Banks, A., Bray-Ward, P., Ward, D., Hudson, T., Gerety, S., Foote, S., Stein, L., Page, D.C., Lander, E.S., Weissenbach, J., Le Paslier, D. and Cohen, D. "A YAC contig map of the human genome. Nature 1995 Sep; 377(6547 Suppl):175-297.
• Bellanne-Chantelot C.; Lacroix B.; Ougen P.; Billault A.; Beaufils S.; Bertrand S.; Georges I.; Glibert F.; Gros I.; Lucotte G.; Susini L.; Codani J.-J.; Gesnouin P.; Pook S.; Vaysseix G.; LU-Kuo J.; Ried T.; Ward D.; Paslier Le; Chumakov I.; Barillot I.; Cohen D. (Sep 1992). "Mapping the whole human genome by fingerprinting yeast artificial chromosomes". Cell. 70 (6): 1059–68. doi:10.1016/0092-8674(92)90254-a.

Most cited publications

• Chumakov, I.M., Rigault, P., Le Gall, I., Bellanne-Chantelot, C., Billault, A., Soularue, P., Belova, M., Sambucy, J-L., Susini, L., ... and Cohen, D. "A YAC contig map of the human genome. Nature 1995 Sep; 377(6547 Suppl):175-297. Cited 363 times according to Google Scholar ^[8]
• Susini L, et al. "Biological models and genes of tumor reversion: Cellular reprogramming through tpt1/TCTP and SIAH-1. Proc Natl Acad Sci U S A 2002 Nov 12;99(23):14976-81. Cited 213 times according to Google Scholar^[8]
• Bellanne-Chantelot,C., Lacroix,B., Ougen,P., Billault,A., Beaufils,S., Bertrand,S., Georges,I., Glibert,F., Gros,I., Lucotte,G., Susini,L., ... and Cohen,D. Mapping the whole human genome by fingerprinting yeast artificial chromosomes. Cell. 1992 Sep 18;70(6):1059-68. Cited 197 times according to Google Scholar ^[8]
• Marcel Tuynder, Giusy Fiucci, Sylvie Prieur, Alexandra Lespagnol, Anne Géant, Séverine Beaucourt, Dominique Duflaut, Stéphanie Besse, Laurent Susini, Jean Cavarelli, Dino Moras, Robert Amson, and Adam Telerman. "Translationally controlled tumor protein is a target of tumor reversion Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15364-9. Cited 169 times according to Google Scholar ^[8]
• Susini L, et al. TCTP protects from apoptotic cell death by antagonizing bax function. Cell Death Differ. 2008 Aug;15(8):1211-20. Cited 143 times according to Google Scholar ^[8]

Patents

• SCREENING METHOD BASED ON SIAH1-NUMB INTERACTION Publication: DE60120220T - 2007-03-29
• Sequences involved in phenomena of tumor suppression, tumor reversion, apoptosis and/or virus resistance and their use as medicines. Publication: US2005221303 - 2005-10-06
• Sequences involved in phenomena of tumor suppression, tumor reversion, apoptosis and/or virus resistance and their use as medicines. Publication: US2004241671 - 2004-12-02
• Compositions and methods for the treatment of cancers: Composition and methods of treating, preventing, and managing cancer by inhibiting the expression of the gene tpt1/TCTP. Publication: US2004087531 - 2004-05-06
• COMPOSITIONS AND METHODS FOR THE TREATMENT OF CANCER Publication: WO03097835 - 2003-11-27
• New human nucleic acid, useful for diagnosis, prognosis and treatment, e.g. of tumors, also related vectors, transformed cell, polypeptides and antibodies. Publication: FR2822475 - 2002-09-27

Genes

• NUMB,^[3]
• SIAH1,^[3]
• TCTP,^[7]

References

1. Kim UJ, Birren BW, Slepak T, Mancino V, Boysen C, Kang HL, Simon MI, Shizuya H (1 Jun 1996). "Construction and characterization of a human bacterial artificial chromosome library". Genomics. 2 (34): 213–8. doi:10.1006/geno.1996.0268. PMID 8661051.
2. Van Orden A, Keller RA, Ambrose WP (1 Jan 2000). "High-throughput flow cytometric DNA fragment sizing". Anal Chem. 1 (72): 37–41. PMID 10655632.
3. Susini L, Passer BJ, Amzallag-Elbaz N, Juven-Gershon T, Prieur S, Privat N, Tuynder M, Gendron MC, Israël A, Amson R, Oren M, Telerman A (18 Dec 2001). "Siah-1 binds and regulates the function of Numb". Proc Natl Acad Sci U S A. 98 (98(26)): 15067–72. doi:10.1073/pnas.261571998. PMC 64984. PMID 11752454.
4. Tuynder M, Susini L, Prieur S, Besse S, Fiucci G, Amson R, Telerman A (Oct 2002). "Biological models and genes of tumor reversion: cellular reprogramming through tpt1/TCTP and SIAH-1". Proc Natl Acad Sci U S A. 99 (23): 14976–81. doi:10.1073/pnas.222470799. PMC 137530. PMID 12399545.
5. Tuynder M, Fiucci G, Prieur S, Lespagnol A, Géant A, Beaucourt S, Duflaut D, Besse S, Susini L, Cavarelli J, Moras D, Amson R, Telerman A (Oct 2004). "Translationally controlled tumor protein is a target of tumor reversion". Proc Natl Acad Sci U S A. 101 (43): 15364–9. doi:10.1073/pnas.0406776101. PMC 523462. PMID 15489264.
6. MacDonald SM, Rafnar T, Langdon J, Lichtenstein LM (August 1995). "Molecular identification of an IgE-dependent histamine-releasing factor". Science. 269: 688–90. doi:10.1126/science.7542803. PMID 7542803.
7. Susini L; et al. (Aug 2008). "TCTP protects from apoptotic cell death by antagonizing bax function". Cell Death Differ. 8: 1211–20. doi:10.1038/cdd.2008.18. PMID 18274553.

External links

• http://www.tumor-reversion.org/
• Search Results for author Susini L on PubMed.
• http://www.nature.com/cdd/journal/v15/n8/full/cdd200818a.html
• http://www.pnas.org/content/99/23/14976.long
• "Mapping the whole human genome by fingerprinting yeast artificial chromosomes". Cell. 70: 1059–1068. doi:10.1016/0092-8674(92)90254-A.
• "A YAC contig map of the human genome". Nature. 377: 175–297. doi:10.1038/377175a0. PMID 7566096.
• http://www.researchgate.net/profile/Laurent_Susini/
• http://cvscience.aviesan.fr/cv/1553/laurent-susini
• http://www.molecular-engines-laboratories.info/html/03-publications.html
• CEPH – Official Site of the CEPH