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Servis Catherine, project leader



Catherine Servis received her PhD from the University of Heriot-Watt in Edinburgh on studies involving the localization, identification and synthesis of the immunodominant determinants of Lactate Dehydrogenase-B4 and IgG2a myeloma protein. After a postdoctoral training at the Basel Institute for Immunology (Hoffmann-La-Roche) she continued her training in protein chemistry at the Friedriech- Miescher Institute (Ciba Geigy –Novartis). In 1990, she joined the Institute of Organic Chemistry of the University of Lausanne where she was involved in the development of strategies for the solid phase synthesis of molecules for biological applications. She joined the Institute of Biochemistry in 1992 and she is heading the Protein and Peptide Chemistry Facility. She is head of the Clinical Tumor Proteome Analysis Facility since May 2005.


Interests: Development of clinical proteomic strategies for the identification and quantification of biomarkers in biofluids and tissue from cancer patients. Development of synthetic tools for biological applications.


Clinical proteomics

Cancer-specific markers in plasma which may be useful for cancer detection and monitoring include proteins released in smaller amounts from cancer tissues (tissue-specific proteins) or as a result of structural and functional changes in the microenvironment surrounding cancer cells. They may also include mediator or effector molecules of the native or acquired immune response to cancer cells (e.g. auto antibodies to cancer-specific proteins). For these reasons, most cancer markers currently in clinical use are low-abundance proteins with concentrations in the nanogram per milliliter range in plasma.

Proteomics technology promises to be a valuable way to identify proteins and fragments thereof present in the tumor environment that may be used to define new molecules for diagnostic, prognostic and therapeutic purposes. Recently, as many as 1261 proteins believed to be differentially expressed in human cancer patients relative to healthy individuals, have been proposed as candidate plasma biomarkers that could be useful in early cancer detection and monitoring, given sufficiently sensitive and specific tests are available for their detection. In the last decade, different proteomics platforms based on Mass Spectrometry (MS), have been developed and used for the identification of cancer-associated proteins and peptides in tissue and serum.



1. The Protein and Peptide Chemistry Facility (PPCF) provides synthetic tools for various biological applications and a variety of analytical and technical services using mass spectrometry to the Lausanne scientific community.
The Facility is also involved in research and teaching on different aspects of protein and peptide chemistry.

2. The Clinical Tumor Protein Analysis Facility (CTPAF, prior within the NCCR program) will be part of the Molecular Biomarker Facility (MBF) of the nascent Lausanne Cancer Center (LCC). The goal of this platform is to develop and optimize strategies for the identification and quantification of molecular markers in biofluids and tissue from cancer patients.

Research projects

1. Monitoring proteins relevant to tumor angiogenesis and tumor progression by proteomic analysis of biofluids and tissue from cancer patients

In collaboration with the groups of C. Ruegg (CePO, LCC, UNIL) M. Hegi (Lab. of Tumor Biology and Genetics, CHUV), R. Stupp (CePO, LCC, CHUV, UNIL), B. Domon and R. Aebersold (IMSB- ETH)

We are following two approaches:

i) Targeted analysis of molecules in biofluids and tissues. In a hypothesis-driven approach we will accurately identify and quantify selected proteins in CSF and serum from patients with multiple glioblastoma or other solid tumors (e.g. colon, breast, head and neck cancers). We will detect molecules that have been previously identified by a single biomarker approach (e.g. VEGF-A, MMP-9) and molecules that have been identified as potential candidates of angiogenesis or tumor progression in gene expression studies (e.g. Cyr61/CCN1; GDF3, GDF-15, EPSTI-1). We will employ a quantitative proteomics approach developed by Aebersold which is based on the selection and chemical synthesis of isotopically labeled reference peptides corresponding to peptides generated from the native protein by tryptic digestion. Since the proteins of interest are glycoproteins, we will use the glycoprotein enrichment method which is developed by the same group and further analysis by LC-ESI MS in SRM/MRM mode in the presence of the reference peptide. This approach has been proven suitable for detecting a panel of candidate biomarkers in clinical samples.

ii) Global protein profiling in biofluids and cancer tissues. Once this first approach has been successfully established, we plan to analyze tumor tissue and biofluids for global protein expression profiles (signatures) specific to the tumor, its propensity to progress (patient survival) and (possibly) its response to therapy. We will study only patients for which clinical follow up and/or patient outcome is known. The proposed strategy involves fractionation of the material to ensure characterization of the different types of components (e.g. small vs large proteins). After immunodepletion of the high abundant proteins, samples will be reduced, alkylated and digested by trypsin and generated peptides separated by 2-D LC and analyzed by MALDI-TOF/TOF. Quantitative differences in the proteins present in tumor tissue or serum/CSF samples will be initially determined through comparison of the peak intensities of their constituent peptides/proteins. Later, when specific peaks have been characterized as interesting, we will quantitate the corresponding proteins by the use of isotopically labeled reference peptides (see above).

2. Mass Spectrometry-based strategy to measure alteration of glycosylation

In collaboration with Bruno Domon, ETH - IMSB.

The aim of this project is to detect the alteration of the glycosylation pattern in the serum of cancer patients by differential analyses using stable isotope labelling. The method developed includes cleavage of N-linked glycans from glycoproteins in serum using PNGase F, and derivatization of the glycans with 2-aminopyridine (or an isotopically labeled variant). The reductively aminated samples are mixed, chemically desialylated and analyzed on a quadrupole time-of-flight system coupled to a micro-HPLC system and a microfluidic device. The different glycoforms are assigned based on their molecular mass, and their structure is confirmed by their MS/MS patterns. The relative ratio of the signal of one glycoform reflects the abundance of the glycan in the two samples.

We will apply this method to the relative quantification of glycans in the serum of patients with colon, breast cancer and controls. In addition to the analysis of the glycans from the whole serum, glycan patterns will also be analyzed after the depletion of the major high abundant proteins in serum. This will provide information about N-glycans from low abundant proteins which may include membrane surface proteins that play an important role in cancer development.

3. The identification of new peptide tumor antigens derived from alternatively spliced variants expressed specifically in neoplastic cells (NCCR)

Within this project, our main focus is the analysis (separation and identification) and quantitation of potential HLA class I-restricted ligands generated by proteasomal degradation of precursor peptides encoded by alternatively expressed exons. The proteolytic activities of other peptidases involved in the antigen processing pathway will also be studied and analyzed.





Peptide Sets: Synthesis of hundreds of free peptides for epitope mapping.


4. Toward error-free do novo peptide sequencing, protein identification and post-translational modification analysis

In collaboration with Prof. Y. Tsybin, Biomolecular Mass Spectrometry Laboratory, LSMB, EPFL

The main goal of the project is to improve the performance of MS-based proteomics analysis and understanding of tandem mass spectrometry fundamentals. The main tasks are related to the development of novel methods of peptide characterization based on sequence dependent retention time (RT) prediction in combination with production abundance analysis based tandem mass spectrometry (MS/MS) and corresponding basic research leading to the application of the novel and improved approaches for analysis of biologically active compounds (peptides).


Peptide Arrays for high throughput screening


2016 |  2014 |  2010 |  2009 |  2007 |  2006 |  2005 |  2004 |  2003 |  2002 |  2000 |  1999 |  1997 |  1995 | 

Balam S., Jafarshad A., Servis C., Frank G., Reed S., Pink R., Druilhe P., Spertini F., Corradin G., 2016. Immunogenicity of dimorphic and C-terminal fragments of Plasmodium falciparum MSP2 formulated with different adjuvants in mice. Vaccine 34(13) pp. 1566-1574. [DOI] [Web of Science] [Pubmed]
Balam S., Olugbile S., Servis C., Diakité M., D'Alessandro A., Frank G., Moret R., Nebie I., Tanner M., Felger I. et al., 2014. Plasmodium falciparum merozoite surface protein 2: epitope mapping and fine specificity of human antibody response against non-polymorphic domains. Malaria Journal 13 p. 510. [Document] [DOI] [Web of Science] [Pubmed]
Céspedes N., Habel C., Lopez-Perez M., Castellanos A., Kajava A.V., Servis C., Felger I., Moret R., Arévalo-Herrera M., Corradin G. et al., 2014. Plasmodium vivax antigen discovery based on alpha-helical coiled coil protein motif. PLoS One 9(6) pp. e100440. [Document] [DOI] [Web of Science] [Pubmed]
Olugbile S., Habel C., Servis C., Spertini F., Verdini A., Corradin G., 2010. Malaria vaccines - The long synthetic peptide approach: Technical and conceptual advancements. Current Opinion in Molecular Therapeutics 12(1) pp. 64-76. [Web of Science] [Pubmed]
Bolhassani A., Ghasemi N., Servis C., Taghikhani M., Rafati S., 2009. The efficiency of a novel delivery system (PEI600-Tat) in development of potent DNA vaccine using HPV16 E7 as a model antigen. Drug Delivery 16(4) pp. 196-204. [DOI] [Web of Science] [Pubmed]
Villard V., Agak G.W., Frank G., Jafarshad A., Servis C., Nébié I., Sirima S.B., Felger I., Arevalo-Herrera M., Herrera S. et al., 2007. Rapid identification of malaria vaccine candidates based on alpha-helical coiled coil protein motif. Plos One 2(7) pp. e645. [Document] [DOI] [Web of Science] [Pubmed]
Chapatte L., Ayyoub M., Morel S., Peitrequin A.L., Lévy N., Servis C., Van den Eynde B.J., Valmori D., Lévy F., 2006. Processing of tumor-associated antigen by the proteasomes of dendritic cells controls in vivo T-cell responses. Cancer Research 66(10) pp. 5461-5468. [DOI] [Web of Science] [Pubmed]
Suarez M., Haenni M., Canarelli S., Fisch F., Chodanowski P., Servis C., Michielin O., Freitag R., Moreillon P., Mermod N., 2005. Structure-function characterization and optimization of a plant-derived antibacterial peptide. Antimicrobial Agents and Chemotherapy 49(9) pp. 3847-3857. [DOI] [Web of Science] [Pubmed]
Chapatte L., Servis C., Valmori D., Burlet-Schiltz O., Dayer J., Monsarrat B., Romero P., Lévy F., 2004. Final antigenic Melan-A peptides produced directly by the proteasomes are preferentially selected for presentation by HLA-A*0201 in melanoma cells. Journal of Immunology 173(10) pp. 6033-6040. [Web of Science] [Pubmed]
Nagorsen D., Servis C., Lévy N., Provenzano M., Dudley M.E., Marincola F.M., Lévy F., 2004. Proteasomal cleavage does not determine immunogenicity of gp100-derived peptides gp100 209-217 and gp100 209-217T210M. Cancer Immunology, Immunotherapy 53(9) pp. 817-824. [DOI] [Web of Science] [Pubmed]
Vuadens F., Crettaz D., Scelatta C., Servis C., Quadroni M., Bienvenut W.V., Schneider P., Hohlfeld P., Applegate L.A., Tissot J.D., 2003. Plasticity of protein expression during culture of fetal skin cells. Electrophoresis 24(7-8) pp. 1281-1291. [DOI] [Web of Science] [Pubmed]
Ayyoub M., Stevanovic S., Sahin U., Guillaume P., Servis C., Rimoldi D., Valmori D., Romero P., Cerottini J.C., Rammensee H.G. et al., 2002. Proteasome-assisted identification of a SSX-2-derived epitope recognized by tumor-reactive CTL infiltrating metastatic melanoma. Journal of Immunology 168(4) pp. 1717-1722. [Web of Science] [Pubmed]
Barceló-Batllori S., André M., Servis C., Lévy N., Takikawa O., Michetti P., Reymond M., Felley-Bosco E., 2002. Proteomic analysis of cytokine induced proteins in human intestinal epithelial cells: implications for inflammatory bowel diseases. Proteomics 2(5) pp. 551-60. [DOI] [Web of Science] [Pubmed]
Burri L., Servis C., Chapatte L., Lévy F., 2002. A recyclable assay to analyze the NH(2)-terminal trimming of antigenic peptide precursors. Protein Expression and Purification 26(1) pp. 19-27. [DOI] [Web of Science] [Pubmed]
Lévy F., Burri L., Morel S., Peitrequin A.L., Lévy N., Bachi A., Hellman U., Van den Eynde B.J., Servis C., 2002. The final N-terminal trimming of a subaminoterminal proline-containing HLA class I-restricted antigenic peptide in the cytosol is mediated by two peptidases. Journal of Immunology 169(8) pp. 4161-4171. [Web of Science] [Pubmed]
Rubio-Godoy V., Ayyoub M., Dutoit V., Servis C., Schink A., Rimoldi D., Romero P., Cerottini J.C., Simon R., Zhao Y. et al., 2002. Combinatorial peptide library-based identification of peptide ligands for tumor-reactive cytolytic T lymphocytes of unknown specificity. European Journal of Immunology 32(8) pp. 2292-2299. [DOI] [Web of Science] [Pubmed]
Miconnet I., Servis C., Cerottini J.C., Romero P., Lévy F., 2000. Amino acid identity and/or position determines the proteasomal cleavage of the HLA-A*0201-restricted peptide tumor antigen MAGE-3271-279. Journal of Biological Chemistry 275(35) pp. 26892-26897. [DOI] [Web of Science] [Pubmed]
Rimoldi D., Rubio-Godoy V., Dutoit V., Lienard D., Salvi S., Guillaume P., Speiser D., Stockert E., Spagnoli G., Servis C. et al., 2000. Efficient simultaneous presentation of NY-ESO-1/LAGE-1 primary and nonprimary open reading frame-derived CTL epitopes in melanoma. Journal of Immunology 165(12) pp. 7253-7261. [Web of Science] [Pubmed]
Valmori D., Gileadi U., Servis C., Dunbar P.R., Cerottini J.C., Romero P., Cerundolo V., Lévy F., 1999. Modulation of proteasomal activity required for the generation of a cytotoxic T lymphocyte-defined peptide derived from the tumor antigen MAGE-3. Journal of Experimental Medicine 189(6) pp. 895-906. [Document] [DOI] [Web of Science] [Pubmed]
Anjuère F., Layer A., Cerottini J.C., Servis C., Luescher I.F., 1995. Synthesis of a radioiodinated photoreactive MAGE-1 peptide derivative and photoaffinity labeling of cell-associated human leukocyte antigen-A1 molecules. Analytical biochemistry 229(1) pp. 61-67. [DOI] [Web of Science] [Pubmed]
Blum-Tirouvanziam U., Servis C., Habluetzel A., Valmori D., Men Y., Esposito F., Del Nero L., Holmes N., Fasel N., Corradin G., 1995. Localization of HLA-A2.1-restricted T cell epitopes in the circumsporozoite protein of Plasmodium falciparum. Journal of Immunology 154(8) pp. 3922-3931. [Web of Science] [Pubmed]
Person Position Contact
Luis Rodrigues Technician Unisciences



Catherine Servis


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