Inge Mertens associate professor

Research Inge Mertens

Research team

Expertise

My research focus is the identification and validation of biomarkers in liquid biopsies, with special interest in extracellular vesicles. We use mass spectrometry based proteomics.

Trapped ion mobility quadrupole time of flight mass spectrometer hyphenated to automated high throughput liquid chromatography. 30/06/2023 - 01/09/2029

Abstract

Proteins are among the most important molecules in our cells and fulfill a whole series of different functions. They provide structure, are the enzymes in metabolic pathways, act as hormones, are secreted by immune cells etc… The structure of each protein is directly encoded by our genes and thousands of different proteins are present in our cell at any given time. Because of there important role, studying proteins in cancer cells or tissues can help understanding how cancer develop, provide leads for new therapy, or provide markers for detection of disease. To study all proteins in a cell (called the proteome) mass spectrometers are used. However, until recently these machines ware not fast and sensitive enough to analyze the proteins in a single cell or fully study how tumor cells interact with the immune system. With the TIMS-TOF mass spectrometer this now is feasible for the first time. In this project application we aim to acquire a Trapped ion mobility Q-Tof mass spectrometer hyphenated with a high throughput and robust nano-scale liquid chromatography instrument. The combination of which will provide us with a versatile tool that can be used for "single" cell proteomics and very sensitive HLA peptide analysis. In addition, in combination with the EVO-SEP one LC system, which is built for robustness and high throughput, the set-up is ideally suited for analysis of clinical samples (e.g. liquid biopsies) in general as up to 100 samples a day can be analyzed. This equipment will open new opportunities for the Center for Oncological Research (CORE) and help it in its mission to develop new detection and stratification methods and new revolutionary therapies for cancer.

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  • Research Project

Center for Proteomics (CfP). 01/01/2022 - 31/12/2026

Abstract

The Center for Proteomics was founded about a decade ago as a UAntwerpen/VITO state-of-the-art mass spectrometry platform as a continuation of the former UAntwerpen CeProMa Core facility. Since 2017, the main focus of the UAntwerpen/VITO team was the use of proteomic approaches to identify biomarkers for early diagnosis of disease. Over the years, we have built up a multi-disciplinary team of lab technicians, mass spectrometry experts, biologists, biochemists, (bio)medical experts, mathematicians and (bio)-informaticians to set up good experimental designs, develop quality control tools, develop additional data analysis software, … Moreover, the close interactions we now have with clinical and academic partners (with complementary expertise and biobanks) give us access to high quality clinical samples and medical expertise. Today, we have the team's expertise, the network and the infrastructure that will help us bridge the gap between discovery, translation and clinical applications. Mass spectrometry based proteomics of biofluids and tissues is complementary to other techniques that are currently available at UAntwerpen. It has the advantage that it can detect modifications and discern various proteoforms. This is not possible with PCR based techniques and even new and promising techniques like single molecule protein sequencing have limitations compared to MS based techniques. Therefore, we make a combination of these techniques in our aim to create an as complete and accurate proteome profile as possible for (bio)medical applications. Besides proteomics, we also specialize in peptidomics, covering the analysis of naturally occurring small peptides which play important regulatory roles in all multicellular organisms and is especially relevant to study cellular interactions of the immune system. This type of analysis requires specialized technological skills, especially in terms of sample preparation, analytical techniques and data analysis. Some team members are worldwide pioneers in this field. This is the reason why several companies (J&J, MyNeo, …) collaborate with the CfP for exactly this type of expert scientific support. Thanks to investments from VITO and UAntwerpen (Hercules) we are equipped with state-of-the art mass spectrometers and hyphenated equipment that rival the best proteomics centers in Europe. Ours Tims-Tof mass spectrometer and Rapiflex maldi imager are unique in Flanders. With this proteomics and peptidomics platform, we focus on application driven research making it possible to work closer with the market than typical academic research groups do. This is a clear added value for both our University, VITO and the industrial partners.

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  • Research Project

Stopping the burden of disease caused by onchocerciasis-associated epilepsy. 01/01/2022 - 31/12/2025

Abstract

There is growing epidemiological evidence that onchocerciasis (river blindness) can cause epilepsy (onchocerciasis-associated epilepsy, OAE), a major unrecognized public health problem in sub-Saharan Africa. However, the pathophysiological mechanism remains unknown. Neither the Onchocerca volvulus, nor its endosymbiont Wolbachia, appear to be able to pass the blood brain barrier (BBB). Annual community-directed treatment with ivermectin (CDTI), has limited efficacy in reducing OAE incidence. Therefore, we will 1] Investigate in onchocerciasis-endemic areas, in Cameroon, whether a community based vector control method "slash & clear" combined with CDTI is superior to CDTI alone to decrease the incidence of OAE; 2] Explore whether O. volvulus excretory/secretory products can cross the BBB and possibly trigger OAE, by comparing proteomic profiles of cerebro-spinal fluid of children with OAE with those of different stages of the parasite; 3] Explore whether O. volvulus infected blackflies may transmit a neutrotropic virus causing OAE, by testing blackflies and sera from OAE cases with Q-PCR targeting potential OAE specific viral sequences identified during a metagenomic case-control study in South Sudan. Our findings will provide context-specific evidence about a complementary strategy to accelerate onchocerciasis elimination and new insights into the underlying mechanisms of OAE, and as such contribute to reducing the burden and stigma of 'river epilepsy'.

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  • Research Project

IMARK. Network for image-based biomarker discovery and evaluation 01/01/2021 - 31/12/2026

Abstract

IMARK capitalizes on the deeply rooted expertise in biomedical imaging at the University of Antwerp to push the boundaries of precision medicine. By resolving molecular and structural patterns in space and time, IMARK aims at expediting biomarker discovery and development. To this end, it unites research groups with complementary knowledge and tools that cover all aspects of imaging-centred fundamental research, preclinical validation and clinical evaluation. IMARK harbours high-end infrastructure for electron and light microscopy, mass spectrometry imaging, magnetic resonance imaging, computed tomography, positron emission tomography and single-photon emission computed tomography. Moreover, IMARK members actively develop correlative approaches that involve multiple imaging modalities to enrich information content, and conceive dedicated image analysis pipelines to obtain robust, quantitative readouts. This unique blend of technologies places IMARK in an excellent position as preferential partner for public-private collaborations and offers strategic advantage for expanding the flourishing IP portfolio. The major application fields of the consortium are neuroscience and oncology. With partners from the Antwerp University Hospital and University Psychiatric Centre Duffel, there is direct access to patient data/samples and potential for translational studies.

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  • Research Project

Extracellular vesicles from urine as source of biomarkers for the diagnosis and follow-up of bladder cancer patients. 30/12/2019 - 29/12/2020

Abstract

Bladder cancer has approximately 2300 new cases in Belgium every year (www.kankerregister.be). Especially in men, bladder cancer is common and is the fourth most common cancer in the world. Nevertheless, the diagnosis of bladder cancer is still not optimal due to the defects of the current standards of urinary cytology and cystoscopy. In addition, the necessary lifelong follow-up makes bladder cancer the most expensive cancer to be treated (Sievert et al., 2009). A non-invasive, cheaper and highly sensitive and specific biomarker set is therefore needed to optimize the diagnosis of bladder cancer on the one hand and to improve the follow-up of low-grade bladder cancer patients on the other. This will improve the quality of life of the patient and decrease the mortality of bladder cancer, the latter through good relapse monitoring, which reduces the risk of metastasis. Exosomes (30-120 nm) are extracellular vesicles (EVs) that are secreted into different body fluids and they contain both RNA, lipids and proteins. They end up in the urine because they are excreted by the epithelia of the urogenital tract. They have enormous diagnostic potential since they play a role in intracellular communication and tumor progression. During the PhD, a method for the purification and characterization of EVs was optimized (results published in JEV). A variant study was performed to determine the interindividual variation at EV protein level. This information has not been known so far, although it is imperative to establish a good discovery experiment capable of identifying an EV protein biomarkers for bladder cancer. The variant study shows that we have to include around 60 samples per experimental group. On the one hand, the urinary EV protein profile of bladder cancer patients will be compared with that of healthy individuals in order to obtain a diagnostic biomarker set. On the other hand, timelines will be established for bladder cancer patients from diagnosis to relapse. By comparing these time points, a biomarker set can be searched for the follow-up of bladder cancer patients. Finally, there will also be a validation study of the potential biomarker sets in a larger population, including patients with other bladder-related pathologies in collaboration with external partners (this validation study is not part of the doctoral work).

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  • Research Project

LC-MS/MS proteome analysis of insect tissues (samples) with gel-free methodology, including -prior to proteome analysis- cellular compartment fractionation of the total proteome and cell membrane proteome extraction with tube-gel technique. 25/06/2019 - 24/06/2021

Abstract

LC-MS/MS proteome analysis of insect tissues (samples) with gel-free methodology, including -prior to proteome analysis- cellular compartment fractionation of the total proteome and cell membrane proteome extraction with tube-gel technique. More specifically: • Proteome isolation will take place from 70 frozen insect tissues (samples) x 2 conditions per sample (soluble fraction, membrane bound faction) • Gel-free LC-MS/MS protocols will be employed on a high-resolution MS instrument. • Cellular fractionation of the total proteome will be done prior to the proteome analysis. • Tube-gel extraction of the membrane proteins will take place.

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  • Research Project

MALDI Mass Spectrometry Imaging (MALDI-MSI): Bridging proteomics and imaging. 01/05/2016 - 30/04/2020

Abstract

The instrument acquired in this project is a matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometer capable of mass spectrometry imaging (MSI). This technique is especially developed for the identification of biomolecules in a manner that retains cytological and histological patterning. This novel technical process, abbreviated to MALDI-MSI represents an interesting and extremely productive intersection between mass spectrometric and imaging platforms. Therefore, this grant is bridging 3 University of Antwerp CORE facilities (Center for Proteomics, Bio-Imaging lab and the Biomedical Microscopic Imaging Core). Using this MALDI-MSI platform, multiple research groups, brought together by a common interest in investigating molecular damage associated with aberrant aging mechanisms, will be able to identify a diverse range of small molecules (peptides and metabolites) as well as larger proteins directly on tissue slides, preserving the topological, histological and cytological data. This is not possible with routine proteomics and metabolomics technologies nor with advanced imaging techniques.

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    • Research Project

    Support maintenance scientific equipment (CEPROMA). 01/01/2016 - 31/12/2019

    Abstract

    This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

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    • Research Project

    CEPROMA: Centre for proteome analysis. Supporting core facilities. 01/10/2015 - 31/12/2021

    Abstract

    This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

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    • Research Project

    Molecular Imaging Mass Spectrometry platform - Nexus of Aging and Disease - an imminent global threat. 06/07/2015 - 31/12/2016

    Abstract

    Mass spectrometry imaging (MSI) is especially developed for the identification of biomolecules in a manner that retains cytological and histological patterning. This novel technical process, abbreviated to MALDI-MSI represents an interesting and extremely productive intersection between mass spectrometric and imaging platforms. Therefore, the postdoc is bridging 3 University of Antwerp CORE facilities (Center for Proteomics, Bio-Imaging lab and the Biomedical Microscopic Imaging Core). Using this MALDI-MSI platform, multiple research groups, brought together by a common interest in investigating molecular damage associated with aberrant aging mechanisms, will be able to identify a diverse range of small molecules (peptides and metabolites) as well as larger proteins directly on tissue slides, preserving the topological, histological and cytological data. This is not possible with routine proteomics and metabolomics technologies nor with advanced imaging techniques.

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      • Research Project

      Urinary exosomes as biomarkers for diagnosis and follow up of bladder cancer patients 02/07/2015 - 30/06/2021

      Abstract

      Bladder cancer is a common urologic cancer with +/-2340 new cases in 2012 in Belgium. The current golden standard for bladder cancer diagnosis is a combination of invasive and non-sensitive urine cytology and cystoscopy. The overall cost of bladder cancer treatment is high due to the long term monitoring of non-muscle –invasive bladder cancer and the treatment of recurrences. Non-invasive, inexpensive and highly sensitive bladder cancer biomarkers are urgently demanded to improve diagnosis and monitoring, and to decrease patient morbidity. Urine exosomes are small membrane vesicles that are released by the epithelia of the complete urogenital tract and contain a variety of molecules such as signal proteins and/or peptides, microRNAs, mRNAs and lipids. In this project we aim to provide urologists with a highly selective, specific and non-invasive exosomal protein signature to diagnose and monitor bladder cancer patients. Therefore we will implement 4 work packages to isolate, identify and compare the exosomal proteome from urine samples of healthy volunteers versus low and high grade bladder cancer patients.

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      • Research Project