Dr. Laura Beretta

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Fred Hutchinson Cancer Research Center
Public Health Sciences Division
Cancer Biology
Associate MemberAppointed: 2004
University of Washington
School of Medicine
Pathology
Affiliate Associate ProfessorAppointed: 2006
Professional Headshot of Laura Beretta

Mailing Address

Division of Public Health Sciences
1100 Fairview Avenue North
(M5-A864)
Seattle, Washington 98109
United States

Contact Information

Phone: (206) 667-7080
Fax: (206) 667-2537
lberetta@fhcrc.org

Qualifications

Ph.D., University of Paris VI, Molecular and Cellular Pharmacology, 1989.

Expertise and Research Interests

1. The importance of translational control in regulating gene expression remains poorly appreciated despite the increasing number of reports describing translational control in the expression of specific genes. Research in my laboratory is aimed at developing a better understanding of the role of translational control by the kinase mTOR (target of rapamycin). We previously demonstrated that rapamycin partially inhibited initiation of translation by activating the inhibitor 4E-BP1. We are using an original application of the DNA microarray technology, in which microarrays are utilized for hybridization of polysome-bound mRNAs, to identify translational targets of mTOR and of 4E-BP proteins. We are also investigating the role of translation in immune cell differentiation, maturation and activation by using knock-out mice for the 4E-BP1 and 4E-BP2 genes.

2. Hepatitis C virus infection affects 3% of the world population (2% of the US population). HCV persists in the large majority of infected patients. We are using a combination of proteomics and gene silencing technologies to identify cellular proteins involved in HCV replication in hepatocytes. Recently, we extended our study to HCV-related hepatocellular carcinoma (HCC). The incidence of HCV-associated HCC is rising in the United States and is likely to triple over the next 10 to 20 years. This new trend is largely due to the high prevalence of HCV infection in the population. The overall survival rate of HCC is poor because most patients are diagnosed when the tumor is in an advanced stage. Our group has embarked on a major effort to integrate genomics, transcriptomics and proteomics for identifying new markers for early HCC diagnosis and for identifying defective signaling pathways and their signature in hepatocytic transformation.

Keywords

COS Keywords:

Cancer Biology, Cancer Or Carcinogenesis, Gene Expression, Hepatitis, Immunology, Microbiology, Pathology, Pharmacology, Public Health, Translation.

Additional Terms:

Gene Expression, Hepatitis C Virus, Liver Cancer, Microbiology, Translational Control.

Languages

(Reading, Writing, Speaking)

English: (Fluent, Fluent, Fluent)
French: (Fluent, Fluent, Fluent)

Memberships

American Association for the Study of Liver Diseases
American Society of Microbiology

Previous Positions

2003-2004, Associate Professor, University of Michigan, Medical School, Microbiology and Immunology
2000-2003, Assistant Professor, University of Michigan, Medical School, Microbiology and Immunology
1996-2000, Independent Investigator, INSERM (Institut National de la Santé et de la Recherche Médicale), Curie Cancer Institute

Patents

Upregulation of Interferon gene expression, Patent Number: , 1998, France.

Funding Received

  • U.S. HHS National Institutes of Health: The University of Michigan Rheumatic Diseases Core Center, , 9/28/01 to 7/31/06.
  • NIDDK: Novel Markers for HCV-related HCC, , 2004 to 2009.
  • NIAID: Functional Analysis of the Role of 4E-BP1 and 4E-BP2 in Translational Control, , 2002 to 2008.
  • Johns Hopkins University: Proteomic Approach for Liver Cancer Biomarker Discovery, , 04/01/2004 to 08/31/2004.

Publications

  • Lai KK, Kolippakkam D, Beretta L (Mar 2008) Comprehensive and quantitative proteome profiling of the mouse liver and plasma., Hepatology, 47 (3), 1043-51 Abstract
  • Yi X, Luk JM, Lee NP, Peng JR, Leng XS, Guan XY, Lau GK, Beretta L, Fan ST (Feb 2008) Association of mortalin (HSPA9) with liver cancer metastasis and prediction of early tumor recurrence, Mol Cell Proteomics, 7 (2), 315-325
  • Parent R, Beretta L (Jan 2008) Translational control plays a prominent role in the hepatocytic differentiation of HepaRG liver progenitor cells., Genome Biology, 9 (1), R19 Abstract
  • Beretta L (Nov 2007) The Human Liver Proteome Project, Mol Cell Proteomics, 6 (11), 2043
  • Beretta L (Oct 2007) Proteomics from the clinical perspective: many hopes and much debate, Nat Methods, 4 (10), 785-6
  • Ioannou GN, Splan MF, Weiss NS, McDonald GB, Beretta L, Lee SP (Aug 2007) Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis, Clin Gastroenterol Hepatol, 5 (8), 938-45
  • Bergeron J, Beretta L (Jul 2007) Barbados Conference 2007, Mol Cell Proteomics, 6 (7), 1287-8
  • Parent R, Kolippakkam D, Booth GC, Beretta L (May 2007) Mammalian target of rapamycin activation impairs hepatocytic differentiation and targets genes moderating lipid homeostasis and hepatocellular growth, Cancer Res, 67 (9), 4337-45
  • Mato JM, He F, Beretta L (May 2007) The 2006 Human Liver Proteome Project (HLPP) Workshops, Proteomics Clin Appl, 1 (5), 442-5
  • Mannova P, Fang R, Wang H, Deng B, McIntosh MW, Hanash SM, Beretta L (Dec 2006) Modification of host lipid raft proteome upon hepatitis C virus replication, Mol Cell Proteomics, 5 (12), 2319-25
  • Feng JT, Shang S, Beretta L (Jun 2006) Proteomics for the early detection and treatment of hepatocellular carcinoma, Oncogene, 25 (27), 3810-17
  • Chignard N, Shang S, Wang H, Marrero J, Bréchot C, Hanash S, Beretta L (Jun 2006) Cleavage of endoplasmic reticulum proteins in hepatocellular carcinoma: detection of generated fragments in patient sera, Gastroenterology, 130 (7), 2010-22
  • Zheng J, Gao X, Beretta L, He F (Mar 2006) The Human Liver Proteome Project (HLPP) Workshop during the 4th HUPO World Congress, Proteomics, 6 (6), 1716-8
  • Parent R, Beretta L (Jul 2005) Proteomics in the study of liver pathology, J Hepatology, 43 (1), 177-83
  • Mannova P, Beretta L (Jul 2005) Activation of the N-Ras-PI3K-Akt-mTOR pathway by hepatitis C virus: control of cell survival and viral replication, J Virol, 79 (14), 8742-9
  • Chignard N, Beretta L (Nov 2004) Proteomics for hepatocellular carcinoma marker discovery, Gastroenterology, 127 (5 Suppl 1), S120-5
  • Barnes BJ, Richards J, Mancl M, Hanash S, Beretta L, Pitha PM (Oct 2004) Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection, J Biol Chem, 279 (43), 45194-207
  • Girard S, Vossman E, Misek DE, Podevin P, Hanash S, Brechot C, Beretta L (Sep 2004) Hepatitis C virus NS5A-regulated gene expression and signaling revealed via microarray and comparative promoter analyses, Hepatology, 40 (3), 708-18
  • Beretta L (May-Aug 2004) Translational control in T lymphocytes, Int Rev Immunol, 23 (3-4), 347-63
  • Rolli-Derkinderen M, Machavoine F, Baraban JM, Grolleau A, Beretta L, Dy M (May 2003) ERK and p38 inhibit the expression of 4E-BP1 repressor of translation through induction of Egr-1, J Biol Chem, 278 (21), 18859-67
  • Richards J, Le Naour F, Hanash S, Beretta L (Dec 2002) Integrated genomic and proteomic analysis of signaling pathways in dendritic cell differentiation and maturation, Ann N Y Acad Sci, 975, 91-100
  • Le Naour F, Brichory F, Beretta L, Hanash SM (Aug 2002) Identification of tumor-associated antigens using proteomics, Technol Cancer Res Treat, 1 (4), 257-62
  • Grolleau A, Bowman J, Pradet-Balade B, Puravs E, Hanash S, Garcia-Sanz JA, Beretta L (Jun 2002) Global and specific translational control by rapamycin in T cells uncovered by microarrays and proteomics, J Biol Chem, 277 (25), 22175-84
  • Girard S, Shalhoub P, Lescure P, Sabile A, Misek DE, Hanash S, Brechot C, Beretta L (Apr 2002) An altered cellular response to interferon and up-regulation of interleukin-8 induced by the hepatitis C viral protein NS5A uncovered by microarray analysis, Virology, 295 (2), 272-83
  • Le Naour F, Brichory F, Misek DE, Brechot C, Hanash SM, Beretta L (Mar 2002) A distinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic analysis, Mol Cell Proteomics, 1 (3), 197-203
  • Dua K, Williams TM, Beretta L (Oct 2001) Translational control of the proteome: relevance to cancer, Proteomics, 1 (10), 1191-9
  • Delhem N, Sabile A, Gajardo R, Podevin P, Abadie A, Blaton MA, Kremsdorf D, Beretta L, Brechot C (Sep 2001) Activation of the interferon-inducible protein kinase PKR by hepatocellular carcinoma derived-hepatitis C virus core protein, Oncogene, 20 (41), 5836-45
  • Podevin P, Sabile A, Gajardo R, Delhem N, Abadie A, Lozach PY, Beretta L, Brechot C (Jun 2001) Expression of hepatitis C virus NS5A natural mutants in a hepatocytic cell line inhibits the antiviral effect of interferon in a PKR-independent manner, Hepatology, 33 (6), 1503-11
  • Le Naour F, Hohenkirk L, Grolleau A, Misek DE, Lescure P, Geiger JD, Hanash S, Beretta L (May 2001) Profiling changes in gene expression during differentiation and maturation of monocyte-derived dendritic cells using both oligonucleotide microarrays and proteomics, J Biol Chem, 276 (21), 17920-31
  • Shalhoub P, Kern S, Girard S, Beretta L (2001) Proteomic-based approach for the identification of tumor markers associated with hepatocellular carcinoma, Disease Markers, 17 (4), 217-23
  • Grolleau A, Kaplan MJ, Hanash SM, Beretta L, Richardson B (Dec 2000) Impaired translational response and increased protein kinase PKR expression in T cells from lupus patients, J Clin Invest, 106 (12), 1561-8
  • Grolleau A, Wietzerbin J, Beretta L (Nov 2000) Defect in the regulation of 4E-BP1 and 2, two repressors of translation initiation, in the retinoid acid resistant cell lines, NB4-R1 and NB4-R2, Leukemia, 14 (11), 1909-14
  • Baron-Delage S, Abadie A, Echaniz-Laguna A, Melki J, Beretta L (Nov 2000) Interferons and IRF-1 induce expression of the survival motor neuron (SMN) genes, Mol Med, 6 (11), 957-68
  • Grolleau A, Sonenberg N, Wietzerbin J, Beretta L (Mar 1999) Differential regulation of 4E-BP1 and 4E-BP2, two repressors of translation initiation, during human myeloid cell differentiation, J Immunol, 162 (6), 3491-7

Profile Details

Last Updated: 5/8/2008

COS Expertise ID #979570
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