Awards ceremony

Best 1' Pitch Presentation Research Day

Announcement by representative of the Student Councils StuGG, StuFF and VDK.

PhD Thesis Prize AY 2019-2020 of the Faculty of Medicine and Health Sciences

Announcement of the laureates by prof. Piet Hoebeke, Dean of the Faculty of Medicine and Health Sciences

1st Laureate: dr. Sander Lefere - Angiogenesis and macrophages as diagnostic and therapeutic targets in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in the liver. Mirroring the obesity pandemic, NAFLD has become the most common chronic liver disease worldwide. The prevalence of complications such as liver cirrhosis and hepatocellular carcinoma (HCC) is increasing further over time, and NAFLD will soon become the leading cause for liver transplantation in many parts of the world. Recent advances have provided insights into the pathogenic mechanisms driving NAFLD. Pathological angiogenesis, the formation of new yet leaky blood vessels, and inflammatory processes controlled by macrophages play major roles in disease progression. Therefore, our work focused specifically on angiogenesis and macrophage-mediated inflammation as targets in NAFLD.

First, we studied the potential of circulating endothelial dysfunction markers and angiogenic factors as diagnostic tools. We found that vascular cell adhesion molecule 1 (VCAM-1) accurately predicts significant liver fibrosis in patients undergoing bariatric surgery. We were able to validate VCAM-1 in two additional cohorts, suggesting that it could facilitate the diagnosis of liver fibrosis in patients with NAFLD.

We next explored the therapeutic potential of inhibiting Angiopoietin-2 (Ang-2). Patients with NAFLD have higher circulating Ang-2 levels, and these levels correlate significantly with hepatic angiogenesis. Importantly, inhibiting Ang-2 in two mouse models reduced inflammation, ballooning and fibrosis, decreased endothelial dysfunction and partially normalized the hepatic macro- and microvascular architecture. One model also led to the development of HCC on a background of NAFLD, which was attenuated by Ang-2 inhibition as well. Thus, this study provided the first evidence of Ang-2 inhibition as a novel therapeutic strategy targeting multiple aspects of the disease.

Finally, we studied peroxisome proliferated-activated receptors (PPARs) activators, drugs targeting multiple metabolic and inflammatory pathways in NAFLD. Specifically, we investigated the efficacy of the pan-PPAR agonist lanifibranor (which activates PPARα, γ and δ) and compared it to the actions of single PPAR agonists in order to dissect the relative contribution of the different PPAR isoforms. Lanifibranor strongly ameliorated all aspects of NAFLD, including liver fibrosis, much more potently than single PPAR agonists. Moreover, lanifibranor treatment drastically reduced the number of hepatic monocytes and monocyte-derived macrophages, which are key immune cells promoting liver inflammation. Coupled with multiple actions on other liver cells, we conclude that lanifibranor potently reduces liver inflammation, in part through direct effects on macrophages.

Promotors: prof. Anja Geerts, prof. Lindsey Devisscher and dr. Christophe Van Steenkiste

2nd Laureate: dr. Edward Geeurickx - Development and application of a biological reference material for extracellular vesicle research

Cells communicate with each other by means of transferring information carriers, such as nucleic acids, proteins or lipids. An efficient way of transferring information carriers is within packages delineated by a double lipid membrane, protecting the cargo against the reducing extracellular environment. Such packages are called extracellular vesicles (EV). Their diameter is in the submicron range, which makes it possible for them to enter the bloodstream and provide a way for intercellular communication at great distances. EV are thought to be involved in multiple diseases, which makes them interesting candidates for diagnosis making and targeted therapy. However, due to a multitude of EV separation and detection methods and the lack of consensus on the use of these methods, limited progress has been made towards clinical application.

To meet the needs of the EV research field, we developed a biological reference material called recombinant EV (rEV), that can assist in the standardization of EV research by providing means for method development, data normalization and calibration. rEV is based on a combination of two proteins (a fusion protein), the HIV1 gag polyprotein, and enhanced green fluorescent protein (EGFP). Gag polyprotein is responsible for vesicle formation and by combining this protein with EGFP, fluorescent vesicles can be formed. By incorporating the DNA sequence for this fusion protein in producer cells, fluorescent vesicles are released in the cell culture supernatant and can be isolated.

We first demonstrated the three most important requirements of a reference material for EV research: 1) physical and biochemical resemblance to EV, 2) differential trackability and discrimination from sample EV and 3) commutability. We identified five distinct detection methods to track and quantify rEV in samples comprising sample EV based on the fluorescence intensity and the protein and RNA content of rEV, allowing their use in any routine laboratory. As proof of concept, we applied rEV as a spike-in material to reveal intra-method and inter-user variability of EV separation methods and additionally normalized EV related data by correcting for this variability. Next, we provided detailed guidelines on the correct use of rEV for method development, data normalization and assessment of pre-analytical variables, all accompanied by experimental examples.

The combination of thorough characterization of rEV and detailed guidelines for application described in this dissertation, should promote the use of reference materials in EV research with the aim of reliably and reproducibly translating results from bench to clinic.

Promotors: prof. Olivier De Wever, prof. An Hendrix and Sven Eyckerman

3rd Laureate: dr. Marie-Angélique De Scheerder - HIV-STAR: HIV-1 Sequencing To identify the Anatomical relevant HIV Reservoir

Although in most cases HIV-1 is nowadays controlled by one single tablet a day, the search for a cure remains important. Not only because of the stigma related to the disease and its transmissibility, the cost, availability and long-term side effects of the medication but also because of the long-term effects on the immune system.

Why is curing HIV-1 so hard? HIV-1 has the capability to hide in specific immune cells. This way it can escape the immune system for years and after stopping the antiviral treatment, the virus can rebound from these cells. To cure HIV-1 we have to tackle this latent reservoir of HIV-1 infected immune cells.

Therefore, a first step is to better understand which cells are contributing to this viral reservoir and this is exactly what we did in the HIV STAR study. By conducting this clinical trial, we were able to show that HIV-1 can rebound from various cell types and various tissue compartments. Furthermore, we were able to show that proliferating cells are more likely to contribute to this replication-competent reservoir. The depth of sampling in this study, the amount of viral sequences analysed and the unique setup and collaboration between participants, the clinic and the lab has led to new insights into the viral reservoir and has important implications for future cure strategies. Moreover, the study allowed us to analyse safety and acceptability of HIV cure and reservoir trials. 

Promotor: prof. Linos Vandekerckhove

PhD Thesis Prize AY 2019-2020 of the Faculty of Veterinary Medicine

Announcement of the laureates by prof. Frank Gasthuys, Dean of the Faculty of Veterinary Medicine

Laureate best non-clinical PhD: dr. Pouya Dini - Parental control of angiogenesis in equine placenta

Normal placental development is crucial for the health of the foal, and alteration in placental development can lead to diseases such as fetal growth retardation in aged mares resulting in the birth of dysmature foals, abnormal placental development in cloned fetuses resulting in neonatal death, placentitis, and hydrops condition. These conditions have one thing in common; they often result in pregnancy loss and cause significant economic losses to the equine industry. With the development of high-dimensional biology, we aimed to shed light on the mechanisms associated with selected placental diseases. At the same time, it has become clear that we need a better general understanding of the mechanisms that regulate normal placental development in mares. This has brought us to investigate the fundamental process of placental vessel formation. We have demonstrated that there is cross-talk between maternal and paternal genes in the placenta. The correct balance between the expression of these genes is essential for the development of the equine placenta, and alteration in the expression of these genes can result in conditions such as excessive edema and hydrops in the fetal membranes. We showed that a paternally expressed gene (RTL1) is crucial for normal placental angiogenesis, while it is regulated by a maternally expressed microRNA (miR-127). The degree of this interaction (between RTL1 and miR-127) still needs to be further elucidated. As more powerful research technology becomes accessible, we need to use this opportunity to elucidate the mechanisms behind the pathologies that continue to limit the productivity of the equine breeding industry.

Promotors: prof. Peter Daels and prof. Barry Ball

Laureate best clinical PhD: dr. Eline Abma - OncoCiDia: an innovative cancer treatment combining a vascular disrupting agent with targeted radiotherapy: preliminary results in dogs

The use of vascular targeting agents as treatment for cancer was first introduced in the 1990’s, when tumour vascularisation came into focus as a potential target for anti-cancer therapy. In this research, the vascular targeting agent combretastatin A4-phosphate (CA4P) was explored for its safety and efficacy in dogs.

In a first step, the potential side effects and toxicity of escalating doses of CA4P were assessed in ten healthy experimental dogs. Upon finding that CA4P was generally well tolerated, it was subsequently administered to eight pet dogs with various spontaneous cancers, to assess its safety and efficacy. At the same time, various ultrasound techniques  were evaluated as assessment tools for vessel perfusion after CA4P-administration. One healthy dog developed weakness in all four limbs that gradually improved over 2 months, and 4 pet dogs displayed side effects that were mild and transient in nature, such as tumour pain. Overall, the CA4P treatment was well tolerated in the dogs with cancer. The ultrasound techniques demonstrated an overall significant reduction in tumour vessel perfusion within 24h after treatment. However, due to the nutritional support of normal vessels of neighbouring healthy tissue, tumour cells in the outer rim of the tumour can survive the treatment and lead to tumour relapse if no complementary treatment is installed. Therefore, the safety and the biodistribution of 131I-hypericin as a potential subsequent treatment modality was investigated in three healthy experimental dogs. Hypericin is attracted to dying cells and transports the 131I to the CA4P-treated tumour areas, where it can irradiate the remaining tumour cells. In the healthy dogs, 131I-hypericin was well-tolerated and all organs were effectively cleared within 7 days. This combination protocol of CA4P-131I-hypericin has been found to be very successful in rodent tumour models. This research has shown both components to be safe when administered to healthy dogs, and CA4P to be both safe and effective when administered to canine cancer patients. With this work, a foundation was laid for further investigation of this combination protocol in canine cancer patients.

Promotors: Prof. Hilde de Rooster, Prof. Sylvie Daminet and Prof. Yicheng Ni

PhD Thesis Prize AY 2019-2020 of the Faculty of Pharmaceutical Sciences

Announcement of the laureate by prof. Jan Van Bocxlaer, Dean of the Faculty of Pharmaceutical Sciences

Laureate: dr. Brecht Vanbillemont - Development and Evaluation of Next-Generation Pharmaceutical Freeze-Drying Technologies

The pharmaceutical industry of the 21st century is facing some challenges due to a changing landscape. With the rise of biopharmaceuticals, product development is becoming more advanced and research more costly. Profound scientific process understanding is promoted and could eventually lead to a high level of automatization and supervisory process control. Process analytical technologies are essential in establishing that goal. Another trend is the transition to continuous processing. These next-generation technologies are developed and evaluated in the thesis in the field of pharmaceutical freeze-drying. One major research section of the thesis focuses on research concerning the freeze-drying of parental unit doss. At first, a high-level supervisory control and optimization algorithm was successfully developed and verified for batch freeze-dryer apparatus that are common in the industry. This next-generation technology is fully compatible with the Quality-by-Design guidelines and allows for a more economical operation of the process while guaranteeing the product quality. Next, process knowledge on the continuous manufacturing of parenteral vials via spin-freeze-drying was deepened. More specifically, the impact of the different spin-freeze-drying process phases on the stability of bio-pharmaceutical formulations was investigated. The research showed that the destabilization mechanisms and their extend were similar in comparison to the current batch freeze-drying methods. At last, an X-ray micro-computed tomography (μCT) based analytical technology was developed, to in-situ image the primary drying phase of spin-frozen vials. This allowed for a mechanistic unravelling of the mass balance of sublimation. The other major research section targeted orally disintegrating tablets (ODTs) manufactured by freeze-drying. To develop the next-generation technologies, a thorough assessment of these tablets were necessary. A systematic evaluation was performed on several commercial ODTs to learn more about the functionality of these products. Next, a successful formulation platform for lyophilized ODTs was developed with new polymeric binders. Finally, a design of continuous manufacturing technology for ODTs was proposed. A Proof-of-Concept (PoC) apparatus was developed and evaluated. The experimental work proved that thermoelectric coolers and heat flux monitoring were suitable for use in such a continuous manufacturing concept.

Promotor: prof. Thomas De Beer

PhD Thesis Prizes AY 2018-2019 (cancelled edition Research Day 2020)

Faculty of Medicine and Health Sciences

  • 1st Laureate (ex aeqou): dr. Sarah Raevens - Advances in the approach to pulmonary vascular complications of liver disease - Promotors: prof. Isabelle Colle and prof. Anja Geerts
  • 1st Laureate (ex aeqou): dr. Nora Sundahl - Boosting anticancer immunity with radiotherapy - Promotors: prof. Piet Ost, prof. Vibeke Kruse and prof. Karel Decaestecker
  • 3rd Laureate: dr. Gaëlle Vanbutsele - Early integration of palliative care in oncology - Promotors UGent: prof. Karen Geboes and prof. Simon Van Belle - Promotors VUB: prof. Koen Pardon and prof. Luc Deliens

Faculty of Veterinary Medicine

  • Laureate best non-clinical PhD: dr. Jolien Van Cleemput - The horse’s respiratory mucosa, airborne pathogens and respirable hazards: the archetypical trifecta of co-evolution - Promotor: prof. Hans Nauwynck
  • Laureate best clinical PhD: dr. Joke Rijckaert - Magnetic motor evoked potentials : a diagnostic test for spinal cord dysfunction in large animals - Promotors: dr. Bart Pardon, prof. Luc Van Ham and prof. Gunther van Loon

Faculty of Pharmaceutical Sciences

  • Laureate: dr. Simon Van Herck - Interactive Polymers for Innate Immune Activation - Promotor: prof. Bruno G. De Geest