Jonas Schröder

• 22 December 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O6
• PhD defence
• Supervisors: prof. S. Truijen, prof. W. Saeys and prof G. Kwakkel

Elissa Embrechts

• 21 December 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O7
• PhD defence
• Supervisors: prof. W. Saeys and prof. S. Truijen

Edgard Dabira

• 21 December 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building R, aula R.109
• PhD defence
• Supervisors: prof. JP. Van geertruyden and prof. U. d'Alessandro

Kristien Vanhaverbeke

• 19 December 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building Q, Promotiezaal
• PhD defence
• Supervisors: prof. S. Verhulst, prof. A. Mulder and prof. B. De Winter

Ilse Van Gucht

• 18 December 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building R, aula R3
• PhD defence
• Supervisors: prof. L. Van Laer, prof. A. Verstraeten and prof. B. Loeys

Carole Mercier

• 15 December 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O8
• PhD defence
• Supervisors: prof. S. Van Laere, prof. P. Meijnders, prof. P. Dirix and prof. D. Verellen

Thuy Ngan Tran

• 14 December 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O4
• PhD defence
• Supervisors: prof. G. Van Hal, prof. M. Peeters and prof. S. Hoeck

David Schieffelers

• 8 December 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building Q, Promotiezaal
• PhD defence
• Supervisors: prof. U. Van Daele and prof. E. van Breda

Stephanie Jordaens

• 1 December 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O1
• PhD defence
• Supervisors: prof. P. Pauwels, prof. W. Tjalma and prof. A. Vorsters

Jeroen Walpot

• 29 November 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O8
• PhD defence
• Supervisors: prof. H. Heidbuchel, prof. C. Van de Heyning and prof. P. Van Herck

Antoine Fourré

• 28 November 2023
• Time: 5 PM - 7 PM
• Venue: UMONS - Auditoire La Fontaine, Centre Vésale, plaine de Nimy, 7000 Mons
• Joint PhD defence
• Supervisors: prof. L. Ris (UMons), prof. N. Roussel and prof. H. Bastiaens

Yaël Hirschberg

• 24 November 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building Q, Promotiezaal
• PhD defence
• Supervisors: prof. I. Mertens, prof. K. Boonen and prof. Y. Vermeiren

Charlotte Rypens

• 20 November 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building R, aula R1
• PhD defence
• Supervisors: prof. L. Dirix and prof. S. Van Laere

Wouter Van Genechten

• 17 November 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O6
• PhD defence
• Supervisors: prof. J. Michielsen, prof. P. Verdonk and dr. S. Claes

Hayat Bentouhami

• 14 November 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building Q, promotiezaal
• PhD defence
• Supervisors: em.prof. J. Weyler and prof. L. Casas

Angela Blasimann Schwarz

• 9 November 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O5
• PhD defence
• Supervisors: prof. D. Vissers and dr. H. Baur

Muhammed Mustafa Sirimsi

• 30 October 2023
• Time: 5:30 PM - 7:30 PM
• Venue: CDE, building O, aula O2
• PhD defence
• Supervisors: prof. P. Van Bogaert, prof. K. Van den Broeck, prof. H. De Loof and dr. K. De Vlieger

Angelina Konnova

• 30 October 2023
• Time: 2 PM - 4 PM
• Venue: CDE, building O, aula O2 - or online​
• PhD defence
• Supervisors: prof. Malhotra S, prof Kumar-Singh S

Vincent Haenen

• 27 October 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O6
• Joint PhD defence
• Supervisors: prof. M. Meeus, prof. A. De Groef, prof. N. De Voogdt (KULeuven) and prof. B. Morlion (KULeuven)

Nanji Lu

• 26 October 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O1 - or online​
• PhD defence
• Supervisors: prof. Koppen C, prof Rozema J, prof Hafezi F

Marijke Leysen

• 25 October 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O8
• Joint PhD defence
• Supervisors: prof. N. Roussel, prof. J. Nijs (VUB) and prof. P. van Wilgen (VUB)

Joyce Bosmans

• 24 October 2023
• Time: 5 PM - 67 PM
• Venue: CDE, building Q, Promotiezaal
• PhD defence
• Supervisors: Prof. V. Van Rompaey, prof. G. Mertens, prof. P. Cras and prof P. zu Eulenburg

Anthe Foubert

• 13 October 2023
• Time: 6 PM - 8 PM
• Venue: CDE, building Q, Promotiezaal
• Joint PhD defence
• Supervisors: prof. N. Roussel, prof. M. Meeus and prof. C. Hermans (UCL)

Anja Brouwer

• 12 October 2023
• Time: 3 PM - 5 PM
• Venue: CDE, building R, room R.103
• PhD defence
• Supervisors: prof S. Van Laere and prof. M. Peeters

Valérie-Anne Chantrain

• 11 October 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building R, aula R3
• Joint PhD defence
• Supervisors: prof. N. Roussel, prof. M. Meeus and prof. C. Lambert (UCL)

Matthias Bosman

• 9 October 2023
• Time: 4.45 PM - 6.45 PM
• Venue: CDE, building O, aula O1
• PhD defence
• Supervisors: prof. E. Van Craenenbroeck and prof. PJ. Guns

Davina Wildemeersch

• 5 October 2023
• Time: 4.00 PM - 6.00 PM
• Venue: CDE, building R, aula R4
• PhD defence
• Supervisor: prof. G. Hans

Lieselotte Knaepen

• 2 October 2023
• Time: 5 PM - 7 PM
• Venue: Hasselt University, Campus Hasselt, auditorium Louis Roppe, Martelarenlaan 42, 3500 Hasselt or online​
• Joint PhD defence
• Supervisors: prof. P. Dendale (Hasselt University), dr. L. Desteghe (Hasselt University & UAntwerpen) and prof. H. Heidbuchel (UAntwerpen)

Sien De Koster

• 27 September 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building Q, promotiezaal
• PhD defence
• Supervisor: em.prof. H. Goossens

ABSTRACT

Multidrug resistance is increasingly observed in human and veterinary medicine worldwide. This major public health challenge is a One Health issue connecting humans, animals and the environment. Insights into the levels of antibiotic resistance in One Health sectors and the pathways that lead to the spread of antibiotic resistance will guide control strategies leading to improved patient care as well as public and animal health.
We employed both phenotypic methods and genomics to investigate the occurrence of antibiotic resistance, the antibiotic use and the dynamics of transmissible resistance genes or isolates within the human and veterinary sectors in Belgium and the Netherlands using a One Health approach.
In this work, we identified and characterized extended-spectrum beta-lactamase (ESBL)-producing, ciprofloxacin-resistant and colistin-resistant Enterobacterales from animals and humans. The carriage of colistin-resistant bacteria by hospitalized patients, healthy individuals from the community and livestock showed that resistance is present in all sectors examined. However, remarkable differences in antibiotic use and resistance were observed between countries and farms. Livestock is a reservoir for a large variety of antimicrobial resistance genes, virulence genes and plasmids. Resistance was spread within a multifaceted landscape of transmission pathways involving both dissemination or a common source of resistant clones and horizontal transfer of plasmids. The complex epidemiology of antibiotic resistance in farms makes it difficult to translate these findings to the impact on human health. However, the pandemic multidrug-resistant clone E. coli ST131 and blaCTX M-15 commonly associated with human infections was rarely found in livestock. Additionally, animal-to-human transmission or vice versa was not detected. Genomic analysis of a global collection of K. pneumoniae ST101 identified ICEKp harboring the yersiniabactin siderophore as a key virulence factor present in hospital-associated isolates. The absence of this siderophore in livestock-associated, community-associated, and food-associated isolates indicates a lower virulence capacity compared to hospital-associated isolates. Taken together, the presence of resistant bacteria in the examined One Health sectors seems to reflect the antibiotic pressure in each sector rather than transmission of resistant isolates between sectors.
In conclusion, this thesis provides insights into the carriage of antibiotic-resistant Gram-negative bacteria by humans and animals and contributes to an improved understanding of the underlying resistance mechanisms and spread of resistance in all One Health sectors involved.

Crispin Lumbala

• 27 September 2023
• Time: 4 PM - 6 PM
• ​Online​
• PhD defence
• Supervisors: prof. JP. Van geertruyden and prof. P. Lutumba

Ilse De Coster

• 25 September 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O7
• PhD defence
• Supervisors: prof. P. Van Damme, prof. K. Maertens, prof. H. Theeten and prof K. Veitch

Dan Bhwana

• 19 September 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O3
• PhD defence
• Supervisors: prof. R. Colebunders and dr. Bruno Paul Mmbando

ABSTRACT

Onchocerciasis, one of the neglected tropical diseases, commonly referred to as “river blindness”, is caused by the Onchocerca volvulus worm, and is transmitted by repeated bites of blackflies. It has been estimated that 20.9 million people are infected worldwide, and 99% of them are living in sub-Saharan Africa (SSA). Increasing epidemiological evidence suggests that onchocerciasis may induce epilepsy; currently called onchocerciasis-associated epilepsy (OAE). In SSA, there may be 200-400,000 persons living with OAE, a condition that we have shown is preventable.

In this PhD thesis we presented findings from different studies that were carried out between 2018 and 2022. We investigated the prevalence, incidence and the clinical aspects of OAE in Mahenge, an onchocerciasis endemic area in Tanzania. We observed a very high prevalence of epilepsy (up to 3.5%) in certain rural villages and 77.9% of the persons with epilepsy met the criteria of the clinical case definition of OAE. OAE presented with a wide spectrum of seizure types including head nodding seizures (nodding syndrome). This high prevalence of OAE was the consequence of on-going O. volvulus transmission because of low ivermectin coverage during the 20 years of community directed treatment with ivermectin (CDTI).

We also used qualitative research methods (focus group discussions and in-depth interviews).  In the rural villages, epilepsy was considered as one of the major health problems in the community, but knowledge on the association between onchocerciasis and epilepsy was limited. Persons with epilepsy are stigmatized and marginalized. Traditional healers are often the first point of care when a person develops epilepsy due to misconceptions surrounding the cause of epilepsy which includes bewitching. Reasons for not taking ivermectin during CDTI were fear of adverse reactions such as itching, swelling and misconception that the drug causes infertility. Challenges for high CDTI coverage included, long walking distance by community drug distributors to deliver drugs to households, persons being away for farming, low awareness of the disease and limited supervision of the distributors.

Finally, we showed that a bi-annual CDTI program with high ivermectin coverage was able to dramatically decrease the epilepsy incidence including the incidence of nodding syndrome.

Overall, this PhD work provides further evidence for the association between onchocerciasis and epilepsy. Moreover, it shows that strengthening onchocerciasis elimination efforts reduces the epilepsy incidence including nodding syndrome in areas with high onchocerciasis transmission.

Thomson Luroni Lakwo

• 19 September 2023
• Time: 2 PM - 4 PM
• Venue: CDE, building O, aula O3
• PhD defence
• Supervisor: prof. R. Colebunders

Marco Bergonti

• 18 September 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building Q, aula Promotiezaal
• PhD defence
• Supervisors: prof. H. Heidbuchel and prof. A. Sarkozy

Karlien Van den Bossche

• 13 September 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building Q, Promotiezaal
• PhD defence
• Supervisors: prof. O. Vanderveken, prof. J. Verbraecken and dr. S. Op de Beeck

Dora Buonfrate

• 31 August 2023
• Time: 4 PM - 6 PM
• Venue: Institute of Tropical Medicine Antwerp, Campus Rochus, Aula Janssens or online​
• PhD defence
• Supervisors: prof. E. Vlieghe, prof. E. Bottieau

Michaël Claessens

• 24 August 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building Q, aula Promotiezaal
• PhD defence
• Supervisor: prof. D. Verellen

Geofrey Makenga

• 4 July 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building Q, aula Promotiezaal
• PhD defence
• Supervisors: prof. JP. Van geertruyden and prof J. Lusingu

Christophe Berkhout

• 30 June 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O5
• PhD defence
• Supervisors: prof. P. Van Royen and prof. L. Peremans

Monjurul Hoque

• 26 June 2023
• Time: 4 PM - 6 PM
  
• ​OnlinePhD defence
• Supervisor: prof. G. Van Hal

Hamid Hassen

• 21 June 2023
• Time: 5:30 PM - 7:30 PM
• Venue: CDE, building O, aula O5
• PhD defence
• Supervisors: prof. H. Bastiaens and prof. S. Abrams

Stefaan Demarest

• 20 June 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O5
• PhD defence
• Supervisor: prof. G. Van Hal

Eva Rens

• 13 June 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O4
• PhD defence
• Supervisors: prof. K. Van den Broeck, prof. R. Remmen and prof. G. Dom

Andreas Domen

• 6 June 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building Q, promotiezaal  
• PhD defence
• Supervisors: prof. M. Peeters, prof. A. Wouters, prof. F. Lardon

Anandhan Dhanasingh

• 8 June 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O5
• PhD defence
• Supervisors: prof. V. Van Rompaey and em.prof. P. Van de Heyning

Maria Ghita

• 7 June 2023
• Time: 2 PM - 4 PM
• Venue: UGhent, classroom Rudolf E. Richter, building 131 Volta, ground floor, Technologiepark Zwijnaarde 131, 9052 Zwijnaarde
  
• Joint PhD defence
• Supervisors: prof. C. Ionescu, dr. D. Copot and prof. D. Verellen

ABSTRACT

This dissertation gives a proof-of-concept for providing complementary information during the decision-making process of lung cancer treatment. This research uses the assessment of lung function and a physiologically based minimal parameter mathematical model to link tumor dynamics and respiratory mechanics. The long-term goal is to provide prognostic and diagnostic patient-specific information with model-based tools, i.e., a framework to hypothesize further prediction of the patient response to treatment.
This work is a hypothesis-building study on lung function assessment in lung cancer patients that provides useful information about changes in respiratory impedance and tissue heterogeneity before and after treatment.
The respiratory impedance is measured with respiratory oscillometry devices and is described based on emerging fractional order impedance models, for evaluating the mechanical behavior of obstructed airways occurring during tumor progression and treatment.
A tumor growth prediction model accounting for pharmacokinetics and pharmacodynamics of specific treatment schedules is proposed using routine measurements of tumor and treatment characteristics to identify the most relevant parameters.
The physiological and identified models of tumor response to specific radiotherapy schedules are employed in a clinical trial, albeit a small cohort of patients diagnosed with lung cancer.
These findings support the long-term goal, and these proof-of-concept results encourage further research in this direction.

Teboho Tiiti

• 6 June 2023
• Time: 4 PM - 6 PM
  
• ​online joint PhD defence
• Supervisors: prof. JP. Bogers, prof. L. Lebelo and prof. G. Selabe

Trakulwong Luecha

• 30 May2023
• Time: 4 PM - 6 PM
• Venue: CDE, building Q, Promotiezaal
• PhD defence
• Supervisors: prof. B. Van Rompaey and prof. L. Peremans

Shinya Tsuzuki

• 30 May 2023
• Time: 10 PM - 12 PM
  
• ​Online PhD defence
• Supervisor: prof. P. Beutels

Kathleen Van Malderen

• 26 May 2023
• Time: 4.30 PM - 6.30 PM
• Venue: UZA, aula Kinsbergen 
• PhD defence
• Supervisors: prof. V. Sabato, prof. H. De Schepper, prof. B. De Winter

Erwin Cornips

• 26 May 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O6
• PhD defence
• Supervisors: prof. T. Menovsky and prof E. Beuls

Gabriel Mertens

• 10 May 2023
• Time: 4:30 PM - 6:30 PM
• Venue: CDE, building O, aula O5
• PhD defence
• Supervisors: prof. M. Meeus and prof. F. Struyf

Willem Boer

• 5 May 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building Q, promotiezaal
• PhD defence
• Supervisors: prof. P. Jorens and prof. E. Hoste

Marika Rasschaert

• 4 May 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O8
• PhD defence
• Supervisors: prof. M. Peeters, prof. P. Van Dam and prof. A. Janssens

Tom Breugelmans

• 2 May 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O1 or online​
• PhD defence
• Supervisors: prof. B. De Winter, prof. A. Smet and prof. H. De Schepper

Laurie Freire Boullosa

• 27 April 2023
• Time: 1 PM - 3 PM
• Venue: CDE, building O, aula O1 or online​
• PhD defence
• Supervisors: prof. F. Lardon, prof. E. Smits and dr. C. Deben

Marta Jiménez García

• 18 April 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O3
• PhD defence
• Supervisors: prof. C. Koppen and prof. J. Rozema

ABSTRACT

Keratoconus is a complex disease that associates myopia, irregular astigmatism, and loss of corneal transparency, resulting in reduced visual quality. A local weak area could be the origin of a cycle of corneal decompensation, leading to insidious corneal thinning and steepening.

Keratoconus clinical management targets disease stabilisation and visual rehabilitation. As of today, corneal crosslinking (CXL) is the only option to halt keratoconus progression, and several studies have demonstrated its safety, with very low rates of associated complications.  Nonetheless, Cochrane reviews have deemed the evidence of CXL insufficient and the lack of a standardised definition of progression was only one of the problems reported.

Our understanding of the natural course of the progressive keratoconus is limited by data availability; CXL meets an unmet clinical need, and most of the progressive cases are nowadays crosslinked to avoid further deterioration. However, although CXL is safe, the do not harm key principle should not be considered sufficient to perform surgery. CXL without properly documented progression would inevitably result in overtreatment —a hindrance for the sustainability of the Public Healthcare Systems— and, more importantly, puts the patients at unnecessary risk.

Large variations in progression speed and patterns have been documented, raising questions about the appropriateness of a unique and overly simplified definition of progression. Customised approaches, based on an objective progression risk assessment, are likely to optimise the clinical outcomes and help to answer: who, when and how to crosslink?

A retrospective longitudinal analysis of more than 700 untreated keratoconus patients is presented in this thesis. Some myths and misconceptions were explored, from the wrong idea that keratoconus implies a protrusion of the cornea to the idea that one definition of progression suits all the cases. Some variables (provided by a corneal tomographer) outperform others when defining progression. Those with an outstanding performance were used to forecast the progressive trend of the disease, which may be an asset to decide on a closer follow-up. Moreover, alternative definitions of progression based on those variables, the definitions used in crosslinking clinical trials and the ones currently in use were explored and put into perspective to match previous clinical knowledge on keratoconus progression. Our results demonstrated that defining progression requires a stratified approach.

At the moment CXL treatment is not reimbursed by the Belgian healthcare services. Hopefully, the recommendations on who and when to crosslink presented here will make CXL accessible for every patient in need.

Wilco Sliedrecht

• 4 April 2023
• Time: 3 PM -  PM
• Venue: online​
• PhD defence
• Supervisors: prof. G. Dom, prof. H. Roozen, prof. K. Witkiewitz 

Ewa Sieliwonczyk

• 21 March 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building Q, Promotiezaal or online​
• PhD defence
• Supervisors: prof. J. Saenen, prof. B. Loeys and dr. D. Schepers

Abstract

Inherited Cardiac Arrhythmia (ICA) syndromes are a group of rare genetic disorders characterised by an increased risk for potentially lethal ventricular arrhythmias, which occur in structurally (seemingly) normal myocardium. While recent technological advances in DNA sequencing have improved in the diagnostic yield in ICA, they have also led to an increased identification of variants of uncertain significance (VUS). Functional characterisation plays a crucial role in variant annotation. Nevertheless, sufficiently high-throughput ICA disease models are still lacking. We set out to fill this gap by generating a zebrafish assay for cardiac arrhythmia, with co-expression of the Ace2N-mNeon genetically encoded voltage indicator and R-GECO genetically encoded calcium indicator in the heart.
Our zebrafish cardiac arrhythmia assay was able to detect electrophysiological abnormalities induced by drugs and genetic models of ICA generated at our lab. These consisted of a long QT syndrome model, induced by a knock-in mutation in the cacna1c gene and a catecholaminergic polymorphic ventricular tachycardia (CPVT) model, due to a homozygous knockout of the casq2 gene. The use of light sheet imaging also enabled us to generate three-dimensional maps of the cardiac action potential characteristics of the entire heart in zebrafish embryos. Additionally, we optimized the process of the generation of zebrafish knock-in mutants through CRISPR-Cas9 gene editing. By combining minimally invasive early genotyping with the Zebrafish Embryo Genotyper device with next-generation sequencing, we were able to achieve an almost seventeen-fold improvement in editing efficiency.
Lastly, we performed clinical and functional assessments of variants in known arrhythmia genes to clarify the remaining issues in ICA genetics. We explored a novel hypothesis of autosomal dominant CPVT for a heterozygous c.738-2A>G splice site variant in CASQ2. We assessed a cohort of (c.4813+3_4813+6dupGGGT) SCN5A founder mutation carriers for clinical signs of a complex genetic architecture in Brugada syndrome. Additionally, we demonstrated the role of the disease model in the functional assessment of the allelic effect of a recurrent KCNQ1 c.1124_1127delTTCA p.(Ile375Argfs*43) variant.
With increased identification of VUS and the confounding contributions of poly- and oligogenic factors, as well as variable allelic effects of established pathogenic variants, the field of ICA genetics research remains complex and challenging. Future studies in promising disease models, such as zebrafish, as well as clinical and molecular investigations in cohorts of patients carrying the same pathogenic variant, will likely aid in clarifying some of the remaining questions.

Ellen Andries

• 16 March 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building Q, Promotiezaal
• PhD defence
• Supervisors: em.prof. P. Van de Heyning, prof. G. Mertens and prof. V. Van Rompaey

Zerihun Zeleke

• 14 March 2023
• Time: 4:45 PM - 6:45 PM
• Venue: CDE, building R, room R.003
• PhD defence
• Supervisors: prof. JP. Van geertruyden, prof. H. Bastiaens and prof. S. Anthierens

Eline Janssens

• 13 March 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building O, aula O8
• PhD defence
• Supervisors: em.prof. J. Van Meerbeeck, prof. K. Lamote and dr. E. Marcq

Ruben De Bosscher

• 28 February 2023
• Time: 5 PM - 7 PM
• Venue: KU Leuven, Promotiezaal Universiteitshal, Naamsestraat 22, 3000 Leuven
• Joint PhD defence
• Supervisors: prof. G. Claessens (KUL) and prof. H. Heidbuchel

Emmanuel Rivière

• 27 February 2023
• Time: 3:30 PM - 5:30 PM
• Venue: CDE, building R, aula R3
• PhD defence
• Supervisors: prof. A. Van Rie and prof. K. Laukens

ABSTRACT

Tuberculosis is a bacterial infectious disease caused by members of the Mycobacterium tuberculosis complex. Antibiotic-resistant bacterial strains are spreading and evolving at an alarming rate. Resistance has been observed to all available tuberculosis antibiotics, threatening the longevity of the currently available treatment options. Whole genome sequencing is a reliable method to infer the drug resistance profile of a Mycobacterium tuberculosis isolate based on the presence of genetic markers of resistance and can support clinical decision-making. Accurate prediction of the drug resistance profile of a Mycobacterium tuberculosis isolate using sequencing relies on curated high-quality databases that contain both high-confidence drug resistance and drug susceptibility genomic markers. To associate variants with drug resistance or susceptibility, a WHO-endorsed standard statistical approach is used. However, this approach is limited when studying new and repurposed antibiotics, due to data scarcity. In the first part of this thesis, we explore the limitations of the WHO-endorsed statistical approach when studying resistance markers of isoniazid, a first-line antibiotic, and bedaquiline, a core drug for the treatment of drug-resistant tuberculosis. In the second part, we explore alternative approaches to infer the bacterial phenotype from variants in the candidate bedaquiline resistance genes. First, we show that the strain genetic background can provide relevant information to interpret the bedaquiline resistance phenotype. Second, we highlight that the integration of expert opinions with the available data improves the genotypic prediction of bedaquiline resistance. Third, while only possible for missense variants, we use sequence- and structure-based features to predict bedaquiline resistance from Rv0678 variants. Lastly, we show that both genetic recombination and recombineering are promising techniques to introduce genomic variants in a clean genetic background to study the phenotypic effect in vitro. In the final part of this thesis, we consider the relevance of the presented findings in the context of the tuberculosis pandemic. To maximize the impact of the findings in this thesis, more efforts are urgently needed to improve the implementation of whole genome sequencing in high tuberculosis burden countries. We hope that the findings and recommendations presented in this work will inspire further research and have a meaningful impact on those suffering from this ancient infectious disease.

Jolein Laumen

• 24 February 2023
• Time: 4 PM - 6 PM
• Venue: Aula Janssens: Institute of Tropical Medicine, Campus Rochus: St-Rochusstraat 43 Antwerp - or online​
• PhD defence
• Supervisors: prof. C. Kenyon, prof S. Malhotra

Abstract:

Gonorrhoea is the second most prevalent bacterial sexually transmittable infection (STI) worldwide. The bacterium Neisseria gonorrhoeae has developed resistance to all currently and previously recommended antibiotics used to treat it. In the first section of this thesis, we investigate the factors underpinning resistance in STI core-groups. We characterized the molecular pathways via which azithromycin resistance emerges in N. gonorrhoeae. In addition to the known macrolide resistance conferring mutations at the target binding site and the efflux pump, we discovered novel ribosomal protein mutations. We show that a population exposed to high levels of antibiotics due to frequent STI screening, has more resistant commensal Neisseria species in their throat compared to the general population. As commensal Neisseria species play an important role in the evolution of antimicrobial resistance in the pathogenic N. gonorrhoeae, including them in monitoring activities could serve as an early warning system. In the second section of this thesis, we evaluate new antibiotic sparing treatment options for gonorrhoea. Although we were unable to isolate bacteriophages effective against currently circulating N. gonorrhoeae strains, throat samples tested did exhibit antigonococcal activity. Bacteriocins, which could be promising alternatives to antibiotics and offer a novel strategy to prevent and treat gonorrhoeae infection, may be responsible for the observed lysis. Next, we assessed the consequences of using mouthwashes as alternative treatment. We report that chlorhexidine sensitivity might diminish after prolonged exposure, and even more concerning, it may cause cross-resistance to antibiotics currently used to treat gonorrhoea. Resistance to Listerine® could not be induced, but daily Listerine® use did influence the oropharyngeal microbiome. These findings imply that mouthwash applications may have unintended consequences and should be carefully considered.

Irina Dumitrescu

• 13 February 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O2
• PhD defence
• Supervisors: prof. T. Dilles en prof. M. Van de Casteele

ABSTRACT

This thesis provides insight in HRM in community care, what the role is of HCN in this matter and what safe HRM care consists of. In community care, high risk medication are considered medications with an increased risk of significant harm to the patient. The consequences of this harm can be more serious than those of other medications. A set of 15 HRM was identified as medications that should primarily be considered HRM by HCN. Standardized HRM care from a HCN is necessary to provide safe HRM care. Specifically for HRM in community care, HCN have a crucial central, coordinating function by regularly acting as the patient’s first point of contact, the last link in the HRM process and the right person to observe the patient and thus to identify problems. By communicating with other stakeholders, by observing the (side) effects of the HRM and the patient’s self-care and medication adherence, by verifying and managing the HRM care, and finally by providing medication care in a competent manner, HCN can contribute to the interprofessional HRM team of healthcare providers around a patient to a significant extent. Organizations and practices are provided a ready to use policy recommendation with a solid scientific foundation, general HRM recommendations and risk-reducing strategies (on 3 levels: organization, care provision and HRM) and finally a more practical ‘translation’ of these recommendations for nursing practice.

Inge Vangenechten

• 3 February 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building Q, Promotiezaal
• PhD defence
• Supervisors: prof. Z. Berneman and prof. A. Gadisseur

Elise Kuylen

• 30 January 2023
• Time: 2 PM - 4 PM
• Venue: CDE, building O, aula O7
• Joint PhD defence
• Supervisors: prof. N. Hens, prof. J. Broeckhove and prof. J. Liesenborghs (UHasselt)

Helena Gossye

• 27 January 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O3
• PhD defence
• Supervisors: prof. C. Van Broeckhoven en prof. S. Engelborghs and prof. P. Cras

Marie-Line Van der Poorten

• 27 January 2023
• Time: 4:30 PM - 6:30 PM
• Venue: CDE, building Q, Promotiezaal
• PhD defence
• Supervisors: prof. V. Sabato, prof. D. Ebo and prof. M. Hagendorens

Nils Helsen

• 16 January 2023
• Time: 5 PM - 7 PM
• Venue: CDE, building O, aula O5
• PhD defence
• Supervisors: prof. S. Stroobants and prof. T. Van den Wyngaert

Ibo Janssens

• 13 January 2023
• Time: 4 PM - 6 PM
• Venue: CDE, building Q, Promotiezaal - or online (with google chrome)
• PhD defence
• Supervisors: prof. I. Wens and prof. N. Cools

Abstract:

Given the increase in global mean prevalence of MS and other autoimmune disease, and the unmet medical need, the quest for new disease-specific treatments continues. In the last decennia, the regulatory mechanisms of the immune system were exploited therapeutically to reshape immune responses and induce durable immune tolerance. Also, adaptive regulatory T cell (Treg) therapy has found its way to the clinic with dozens of clinical trials ongoing and finished. To date, researchers seek to augment clinical efficacy by using a broad range of molecular engineering methods with the first clinical trials using engineered Tregs ongoing. The general aim of this thesis was to develop a clinically safe vaccine for the treatment of MS, based on Tregs specifically targeting cells involved in the onset and progression of the disease. In addition, we provide an alternative for currently used engineering methods, which have shown pre-clinical efficacy and thus clinical potential, but also possess multiple safety concerns. In doing so, we aimed to advance the field of Treg therapy by providing in vitro proof of TCR-encoding mRNA-transfected Tregs and we are convinced that the work presented in these thesis will play its part in the road to long-lasting tolerance in MS and other autoimmune diseases.