An author’s perspective: Christophe Hirtz on LC–MRM in human saliva studies


To help provide insight into the recent article published in Bioanalysis: Assessing a multiplex targeted proteomics approach for the clinical diagnosis of periodontitis using saliva samples, we spoke with author Christophe Hirtz, Professor of Biochemistry and Clinical Proteomics at Montpellier University (Montpellier, France). Christophe explains why he felt this was an important area for bioanalysis and worthy of publication. With over 20 years of experience in biomarker discovery, his work focuses on LC–MRM in saliva studies.

Headshot“I started my career in research studying Biochemistry at Paul Sabatier University (Toulouse, France). After working as a Research Technician for 12 years, I received my Doctorate (2005) and an accreditation to supervise research (2010) in the clinical proteomics field. In 2008, I became Associate Professor at the University of Montpellier (Montpellier, France) in Biochemistry and Clinical Proteomics. My scientific interests include the development of innovative methods for protein quantification using targeted mass spectrometry in a clinical environment. I have been responsible for the Clinical Proteomics Platform of Montpellier, a nationally recognized platform (ISO certified), since 2010. This role relies on expertize in large scale and targeted analysis of human samples using relevant approaches (LC–MS/MS, HR/MS, SRM/MRM, multiplex ELISA) and biostatistics and bioinformatics data analysis. I have been a member of the International Federation of Clinical Chemistry since 2013 and have also recently obtained a full professor position in Biochemistry and Clinical Proteomics in 2017.”

1. What inspired you to work in this field of bioanalysis?
I started my career as a physiologist, interested in biological processes at a cellular level and at the human body level, and I was curious to find out how all of these biological process worked. Rapidly, as a Research Technician, I was implicated in the use and development of different technologies such as western and northern blots. From there, I understood that bioanalysis was definitely my field of interest and that interest grew significantly as I discovered mass spectrometry (MS) in 1999. This outstanding technology, allowing the direct identification of proteins and their post-translational modification was a real cutting-edge methodology that I knew that I would like to dive into. I was lucky enough to have the opportunity (thanks to my mentor, Professor Deville de Périère) to use and later to develop one of the first MS systems installed for protein analysis (Biflex II, Bruker) in a research lab of the French National Institute for Agricultural Research (Paris, France).

I specialized in the field of human salivary research, which was supported by the dental school of Montpellier (Montpellier, France). We were one of the first groups in the world to publish a new complex salivary proteome and to then participate in a way to revive salivary research interest.


2. What impact would you like to see/expect to see as a result of your publication?
I see two main impacts with this publication. Firstly, the demonstration of salivary samples as a niche area of interest for biomarker studies in an array of systemic and local pathologies like Periodontitis. Using saliva samples is non-invasive, inexpensive, and saliva contains more than 3000 differently expressed proteins and peptides. We have entered the era of saliva-omics technology and saliva diagnostics with a high translational potential.

Secondly, our study shows that targeted mass spectrometry approaches like LC–MRM could be routinely used in a clinical environment. Specific, sensitive and reliable, LC–MRM method can help to screen and diagnose many different pathologies, bringing a non-negligible added value to the classic ELISA test.

3. What are the next steps for your research and this field of bioanalysis?
The Clinical Proteomics Platform I am heading with Professor Lehmann (University Hospital Montpellier; France) is highly implicated in research programs including the development of mass spectrometry based approaches in a clinical environment. For example, we have a really important ANR project (BUVAMASS, ANR-15-CE18-0011) dealing with the use of dried blood spot (DBS) for clinical mass spectrometry analysis in partnership with Spot To Lab company. The rationale is to set up a quantitative mass spectrometry detection method of peptide and proteins from DBS. All of them belong to the list of the clinical biomarkers referenced by the French Ministry of Health. We are currently assessing and validating the clinical grade quality of this MS detection in concordance with clinical norms (ISO15189) already in place in our laboratory. This breakthrough technology could complement eMedicine and patient therapeutic education as blood samples could be collected by the patient at home or at the physician’s practice without being sent to the laboratory for analysis.

4. Are there any researchers/projects/technologies that you are watching at the moment, and any you think we should be keeping an eye on?
We are following a lot of researchers in the clinical proteomics field but are especially interested in the new Parallel Accumulation Serial Fragmentation (PASEF) acquisition method of Bruker (timsTOF PRO) allowing extremely high speed and sensitivity to reach new depths in shotgun proteomics. This new technology opens new perspectives in the bioanalysis of proteins and peptides.

5. Do you have any advice for anyone who may be interested in working in this field?
I would say to meet a specialist ‘in real life’, discuss the pros and cons of the technology and do not hesitate to contact recognized mass spectrometry platforms. As scientists in the clinical field, we are ready to share our knowledge in order to benefit the patients.

Reference: Mertens B, Orti V, Vialaret J et al. Assessing a multiplex targeted proteomics approach for the clinical diagnosis of periodontitis using saliva samples. Bioanalysis 10(1), dio:10.4155(2017) (Epub ahead of print)

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