Award ceremony

The following laureates will be honoured at the award ceremony. Recording here

Best 1' Poster Pitch Presentation

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

PhD Thesis Prize AY 2020-2021 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. Cedric Bosteels - The role of DC subsets in respiratory viral infections and vaccination: a case of mistaken identity

Respiratory viruses pose a constant threat to our health and normal way of living. When these viruses enter our lungs, our body alarms various kinds of immune cells to eliminate these harmful microorganisms. One of these immune cells, called the dendritic cell or DC, coordinates the attack against the encountered threat. With their ‘dendrites’, DCs probe the crime scene and capture material from the invader, known as antigen, and integrate all this information to optimally instruct other immune cells such as T cells to eliminate the virus. We have uncovered the true identity of a new DC subset, coined inflammatory-DC (or inf-cDC2), that arises in the lung of mice infected with viruses relevant to human kind. In the past these inf-cDC2s have been misconceived as monocyte-derived cells, however we have found that they are very different from these cells. The power of inf-cDC2s is their ability to combine features previously attributed to other immune cells to induce the best form of immunity. Next to respiratory viral infections, we also discovered a crucial role for inf-cDC2s in a model of vaccination. In the future it will be crucial to identify the human counterpart of inf-cDC2s and to investigate in which other diseases these cells arise. Altogether our findings could contribute to the development of therapeutic interventions, for instance by designing vaccines to trigger the formation of inf-cDC2s and thus generate stronger protective immune responses.

Promotor: prof. Bart Lambrecht

2nd Laureate: dr. Joeri Tulkens - Circulating bacterial vesicles: from discovery towards clinical application

All cells, including human and bacterial cells, secrete nanometer-sized packages of proteins and nucleic acids contained within a lipid membrane. These packages are called eukaryotic extracellular vesicles (EEV) in case of a human origin and bacterial extracellular vesicles (BEV) if they originate from bacterial cells. EV are thought to be involved in the pathogenesis of multiple diseases and this makes them attractive candidates for diagnosis and targeted therapy. However, to uncover the full biomarker potential of EEV and BEV and enable the clinical application of these vesicles, extensive research is needed.

During the first part of this PhD project, the combination of size-exclusion chromatography and density gradient centrifugation was used to identify the biomolecular composition and dynamics of lipoprotein particles (LPP) and EEV in serial blood plasma samples. Analysis of these lipid-carrying particles from breast cancer, ovarian cancer and HIV patients indicated that EEV carry a unique, dynamic and context-dependent protein composition, and miRNA and tRNA profile, which are not directly measurable in LPP and total blood plasma, respectively. This novel fractionation strategy substantially advanced the biological understanding and biomarker development of systemically circulating lipid-carrying particles.

In the second part of this dissertation, it was shown for the first time that BEV secreted by gut bacterial cells can reach the systemic circulation during certain clinical conditions characterized by an impaired gut barrier (IBD, HIV and cancer). These experimental data provided a new mechanism on how gut bacteria are able to communicate with the host at a distance, which was an eye-opener in the scientific community. Systemic BEV were fully characterized and the diagnostic potential of these bacterial vesicles to detect gut barrier dysfunction was demonstrated. Studying mouse models, this PhD project unraveled how BEV from human gut microbiota help shape the anticancer immune response induced by certain chemotherapy. Finally, guidelines and a step-by-step protocol for BEV separation and characterization from human body fluids was provided to the scientific community.

Taken together, the extensive EEV and BEV research performed during this PhD project provides a leap forward towards the clinical application of both subtypes of EV.

Promotors: prof. An Hendrix and prof. Jo Vandesompele

3rd Laureate (ex aequo): dr. Renate De Smedt - Finding the ‘key’ in leukemia: PIM1 inhibition as a novel therapy in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia and lymphoma (T-ALL/T-LBL) are aggressive blood cancers that are treated with, among others, glucocorticoids, a drug for which a number of patients show gradual resistance. Moreover, the outcome for patients that relapse is extremely poor. Therefore, novel targeted therapies that focus on reducing the risk for relapse via increasing the sensitivity towards glucocorticoids are highly needed.

In this PhD, we have identified a novel T-cell receptor β driven translocation, t(6;7)(p21;q34), causing aberrant activation of the oncogenic kinase PIM1 in a case of pediatric T-LBL. Expression analysis of primary patient samples and normal human T cell counterparts revealed that PIM1 activation is a frequent oncogenic event in T-cell tumors. The search towards novel therapeutic strategies has largely focused on cell intrinsic properties of the tumor cell. However, non-cell autonomous activation of oncogenic pathways might also offer novel therapeutic opportunities. Indeed, our work revealed that IL7 and glucocorticoids drive aberrant activation of PIM1 and suggests that IL7 responsive T-ALL/T-LBL patients could benefit from PIM inhibition. To this end, we showed via in vivo drug profiling experiments that patient-derived xenograft models of PIM1high and IL7 responsive T-ALL/T-LBL tumors are sensitive to PIM1 inhibition. Moreover, PIM1 inhibition synergistically affects leukemia progression in combination with glucocorticoids, due to acute glucocorticoid induced PIM1 activation in residual human T-ALL/T-LBL cells and loss of anti-apoptotic MCL1 upon PIM1 inactivation. In conclusion, our work provides a rationale for including T-ALL/T-LBL patients in clinical trials for PIM inhibitors in combination with conventional chemotherapeutics.

Promotors: prof. Pieter Van Vlierberghe and prof. Steven Goossens

3rd Laureate (ex aequo)dr. Juliette Roels - The epigenetic landscape of normal and malignant T cell development

T cells are an essential part of the human immune system. These cells help fight infections and cancer cells. However, when their development is de-regulated, these normal T cells can alter into malignant, leukemic cells. This results in T cell acute lymphoblastic leukemia or T-ALL, an aggressive type of blood cancer that mainly affects children. T-ALL patients can be treated with an intensified chemotherapy, which has significantly improved the survival of these patients. However, the (long-term) side effects and the impact on the quality of life of these patients is substantial.

In this PhD thesis, entitled “The epigenetic landscape of normal and malignant T cell development”, under guidance of promoters Prof. Dr. Pieter Van Vlierberghe and Prof. Dr. Tom Taghon, we have studied the epigenetic landscape of T-ALL and its normal developing T cell  counterparts. We find that each T cell stage has its own set of different epigenetic modifications that is important at several developmental checkpoints to guide the cells further in their maturation towards normal and functional immune cells. Furthermore, in T-ALL, we find two types of patients with different epigenetic profiles. Using this epigenetic information, we discovered that in one subtype of T-ALL, preleukemic cells were long present before the diagnosis. In the other subset of T-ALL patients, the leukemia progressed rapidly and little alterations in the epigenetics could be observed. Despite these differences, both patient groups responded well to treatment with an epigenetic inhibitor, which significantly increased survival for both compared to the controls.

Promotors: prof. Pieter Van Vlierberghe and prof. Tom Taghon

PhD Thesis Prize AY 2020-2021 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. Robert Jansens - Taking control - alphaherpesvirus manipulation of the cytoskeleton and the epitranscriptome

 Herpesviruses are master manipulators of the host cells that they infect. Over millions of years of co-evolution with the host, herpesviruses have developed countless strategies to maximize the efficiency of their replication, and to counteract antiviral mechanisms of the host. During my PhD we discovered two novel strategies used by alphaherpesviruses to manipulate RNA processing. We found that alphaherpesviruses, but not other herpesviruses, trigger preferential degradation of methylated cellular transcripts. Degradation of transcripts is driven by the cytoplasmic YTHDF m6A reader proteins, and correlates with an enhanced localization of YTHDF proteins to enlarged P-bodies in infected cells. Degradation of m6A-containing transcripts is not essential for viral replication in cell culture, but suppresses expression of antiviral type I interferon and interferon sensitive gene (ISG) transcripts. On the other hand, we discovered that alphaherpesvirus kinases phosphorylate several components of the m6A methyltransferase complex, including METTL3, METTL14 and WTAP. Phosphorylation of these proteins correlates with inhibition of the m6A methyltransferase complex and a near complete loss of m6A levels in alphaherpesvirus-infected cells. Expression of the viral serine/threonine protein kinase US3 is necessary and sufficient for phosphorylation of METTL3 and METTL14 and inhibition of the m6A methyltransferase complex. Together, these findings represent the first evidence of a virus inhibiting m6A methylation and the first evidence of virus induced degradation of m6A containing transcripts.

Promotor: prof. Herman W. Favoreel

Laureate best clinical PhD: dr. Jade Bokma - Innovations in rapid Mycoplasma bovis diagnostics with MALDI-TOF MS and nanopore sequencing

Mycoplasma bovis is a primary cause of pneumonia in calves, resulting in impaired animal welfare, high antimicrobial use, and huge economic losses in all cattle sectors worldwide. For a better control and treatment success both rapid identification of M. bovis and antimicrobial susceptibility testing (AST) are key, as no commercial vaccine was available in Europe. Present diagnostic methods for identification (e.g. culture, qPCR) have several drawbacks, such as costs, diagnostic accuracy, and in particular a long turnaround time. Also, no routine antimicrobial susceptibility testing is performed and a reference framework for resistance determination is lacking. Therefore, the general aim of this thesis was to develop new MALDI-TOF-MS and nanopore sequencing based diagnostic methods, and to apply those methods on Belgian field samples, gaining better insight into the epidemiology of M. bovis. The developed diagnostic methods for rapid identification, antimicrobial susceptibility testing, and strain typing of M. bovis from respiratory tract samples are complementary and immediately applicable in peripheral laboratories. Together with these new methods, also substantial epidemiological information came to light, showing the importance of a more national approach for the prevention of introducing M. bovis into the herd and country. In conclusion, the results of this thesis are a major step towards better prevention and control of M. bovis in cattle.

Promotors: prof. Bart Pardon, prof. Freddy Haesebrouck, and Dr. Filip Boyen

PhD Thesis Prize AY 2020-2021 of the Faculty of Pharmaceutical Sciences

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

Laureate: dr. Annemiek Uvyn  - Multivalent antibody recruiting molecules as a novel type of cancer immunotherapy

The general aim of this thesis was to design multivalent antibody recruiting molecules (ARMs) as a novel type of cancer immunotherapy. ARMs are synthetic bifunctional molecules which can introduce antibodies onto a disease-relevant target. As an alternative to the use of externally administered monoclonal antibodies, exploiting the presence of endogenous antibodies that are present in the serum of every human being could be attractive. ARMs consist of a target binding terminus (TBT) which can interact with a pathogen or cancer cell surface and a hapten as an antibody binding terminus (ABT) that can bind endogenous anti-hapten antibodies. By doing so, a ternary complex is formed between the pathogen or cancer cell of interest, the ARM and the antibody. The subsequent clustering of antibodies on a target surface is capable to induce antibody-mediated immune responses including antibody dependent cellular cytotoxicity (ADCC), complement dependent cytotoxicity (CDC) and antibody dependent cellular phagocytosis (ADCP), to kill the target.  The design of multivalent macromolecules consisting of multiple ABTs and/or TBTs could be an added value in efficiently recruiting antibodies towards a cell surface and subsequent induction of innate cell killing.

Promotor: prof. Bruno De Geest