Laurent Susini

Last updated
Laurent Susini
Nationality French
Alma mater Paris Diderot University
Titleassociate Professor, PhD
Scientific career
Fields Oncology research; tumor reversion; TCTP
InstitutionsCEPHB-Fondation Jean Dausset; Caltech; Genethon; Los Alamos National Lab; Genset; Novartis

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.

Contents

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 collaborated with research teams from Caltech [1] and the Los Alamos National Lab. [2] as a member of Pr Daniel Cohen  [ fr ]'s team at Genethon and at Genset Corporation to contribute to the first physical map of the human genome.

At the Weizmann Institute of Science, in the Lab of Professor Moshe Oren, he demonstrated that SIAH1 induces ubiquitin-mediated degradation of NUMB (gene), a protein that influences cell fate decisions. [3] SIAH1 a p53-inducible gene, plays a role in both cell death and tumor suppression by targeting specific proteins for proteasomal degradation via ubiquitination.

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 analyzing gene expression and using bio-informatics on cellular models of tumor reversion, M.E.L. researchers identified over 200 genes involved in the process, including TCTP (Translationally Controlled Tumor Protein / Translationally Controlled Tumour Protein. This research has led to the potential development of drugs for cancer prevention and management by inhibiting tpt1/TCTP gene expression.

Laurent Susini joined Oncology Clinical Research in 2007 to contribute to the early clinical development of anti-cancer drugs. He worked first with Quintiles and later joined the Translational Clinical Oncology department at the Novartis Institutes for BioMedical Research, where he designed and conducted phase I clinical trials primarily in melanoma and hematology 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]

Most cited publications

Patents

Genes

Related Research Articles

<span class="mw-page-title-main">Apoptosis regulator BAX</span> Mammalian protein found in Homo sapiens

Apoptosis regulator BAX, also known as bcl-2-like protein 4, is a protein that in humans is encoded by the BAX gene. BAX is a member of the Bcl-2 gene family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein forms a heterodimer with BCL2, and functions as an apoptotic activator. This protein is reported to interact with, and increase the opening of, the mitochondrial voltage-dependent anion channel (VDAC), which leads to the loss in membrane potential and the release of cytochrome c. The expression of this gene is regulated by the tumor suppressor P53 and has been shown to be involved in P53-mediated apoptosis.

p53 upregulated modulator of apoptosis Protein-coding gene in the species Homo sapiens

The p53 upregulated modulator of apoptosis (PUMA) also known as Bcl-2-binding component 3 (BBC3), is a pro-apoptotic protein, member of the Bcl-2 protein family. In humans, the Bcl-2-binding component 3 protein is encoded by the BBC3 gene. The expression of PUMA is regulated by the tumor suppressor p53. PUMA is involved in p53-dependent and -independent apoptosis induced by a variety of signals, and is regulated by transcription factors, not by post-translational modifications. After activation, PUMA interacts with antiapoptotic Bcl-2 family members, thus freeing Bax and/or Bak which are then able to signal apoptosis to the mitochondria. Following mitochondrial dysfunction, the caspase cascade is activated ultimately leading to cell death.

<span class="mw-page-title-main">TSG101</span> Protein-coding gene in the species Homo sapiens

Tumor susceptibility gene 101, also known as TSG101, is a human gene that encodes for a cellular protein of the same name.

<span class="mw-page-title-main">AKT2</span> Protein-coding gene in the species Homo sapiens

AKT2, also known as RAC-beta serine/threonine-protein kinase, is an enzyme that in humans is encoded by the AKT2 gene. It influences metabolite storage as part of the insulin signal transduction pathway.

<span class="mw-page-title-main">BAG1</span> Protein-coding gene in the species Homo sapiens

BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the BAG1 gene.

<span class="mw-page-title-main">SIAH1</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase SIAH1 is an enzyme that in humans is encoded by the SIAH1 gene.

<span class="mw-page-title-main">NUMB (gene)</span> Protein-coding gene in the species Homo sapiens

Protein numb homolog is a protein that in humans is encoded by the NUMB gene. The protein encoded by this gene plays a role in the determination of cell fates during development. The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Four transcript variants encoding different isoforms have been found for this gene.

<span class="mw-page-title-main">DNAJA3</span> Protein-coding gene in the species Homo sapiens

DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the DNAJA3 gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known for binding and activating Hsp70 chaperone proteins to perform protein folding, degradation, and complex assembly. As a mitochondrial protein, it is involved in maintaining membrane potential and mitochondrial DNA (mtDNA) integrity, as well as cellular processes such as cell movement, growth, and death. Furthermore, it is associated with a broad range of diseases, including neurodegenerative diseases, inflammatory diseases, and cancers.

<span class="mw-page-title-main">Frizzled-7</span> Protein-coding gene in the species Homo sapiens

Frizzled-7(Fd-7) is a protein that in humans is encoded by the FZD7 gene.

<span class="mw-page-title-main">INHA</span> Protein and coding gene in humans

Inhibin, alpha, also known as INHA, is a protein which in humans is encoded by the INHA gene.

<span class="mw-page-title-main">Translationally controlled tumor protein</span> Protein-coding gene in the species Homo sapiens

Translationally controlled tumor protein (TCTP) is a protein that in humans is encoded by the TPT1 gene. TPT1 is mapped to 13q12-q14 on chromosome 13. The human gene contains five introns and six exons, TPT1 contains a promoter with a canonical TATA-box and several promoter elements, which are well-conserved in mammals. The assay with reporter gene exhibits a strong promoter activity comparable to viral promoters.

<span class="mw-page-title-main">CCT5 (gene)</span> Protein-coding gene in the species Homo sapiens

T-complex protein 1 subunit epsilon is a protein that in humans is encoded by the CCT5 gene.

<span class="mw-page-title-main">HIC1</span> Protein-coding gene in the species Homo sapiens

Hypermethylated in cancer 1 protein is a protein that in humans is encoded by the HIC1 gene.

<span class="mw-page-title-main">MADD (gene)</span> Protein-coding gene in the species Homo sapiens

MAP kinase-activating death domain protein is an enzyme that in humans is encoded by the MADD gene.

<span class="mw-page-title-main">RECK</span> Protein-coding gene in the species Homo sapiens

Reversion-inducing-cysteine-rich protein with kazal motifs, also known as RECK, is a human gene, thought to be a metastasis suppressor.

<span class="mw-page-title-main">BNIP3L</span> Protein-coding gene in the species Homo sapiens

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like is a protein that in humans is encoded by the BNIP3L gene.

<span class="mw-page-title-main">MOAP1</span> Protein-coding gene in the species Homo sapiens

Modulator of apoptosis 1 is a protein that in humans is encoded by the MOAP1 gene.

<span class="mw-page-title-main">TUSC3</span> Protein-coding gene in the species Homo sapiens

Tumor suppressor candidate 3 is a protein that in humans is encoded by the TUSC3 gene.

<span class="mw-page-title-main">BCAS1</span> Protein-coding gene in the species Homo sapiens

Breast carcinoma-amplified sequence 1 is a protein that in humans is encoded by the BCAS1 gene.

<span class="mw-page-title-main">STEAP3</span> Protein-coding gene in the species Homo sapiens

Metalloreductase STEAP3 is an enzyme that in humans is encoded by the STEAP3 gene.

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. 34 (2): 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. 72 (1): 37–41. doi:10.1021/ac990782i. PMID   10655632.
  3. 1 2 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 (26): 15067–72. Bibcode:2001PNAS...9815067S. 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. Bibcode:2002PNAS...9914976T. 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. Bibcode:2004PNAS..10115364T. 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 (5224): 688–90. Bibcode:1995Sci...269..688M. doi:10.1126/science.7542803. PMID   7542803.
  7. 1 2 Susini L; et al. (Aug 2008). "TCTP protects from apoptotic cell death by antagonizing bax function". Cell Death Differ. 15 (8): 1211–20. doi: 10.1038/cdd.2008.18 . PMID   18274553. S2CID   27393934.
  8. 1 2 3 4 5 "Google Scholar".
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