Guest speakers

09:15 - Welcome

Welcome speech by prof. Guy Joos (Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences) and prof. Tom Coenye (Department of Pharmaceutical analysis, Faculty of Pharmaceutical Sciences)

Welcome speech by prof. Rik Van de Walle, rector of Ghent University

09:30 - Lecture 'Stem cells and cancer'

Guest speaker: Prof. Cédric Blanpain (Laboratory of stem cells and cancer, Université libre de Bruxelles (ULB)) 

Cédric Blanpain' group uses lineage-tracing approaches to study the role of stem cells during development, homeostasis and cancer. His group uncovered the existence of stem cells and progenitors acting during homeostasis and repair of the epidermis and uncovered a novel paradigm of lineage segregation in the mammary gland and prostate. His lab was pioneered in using mouse genetics to identify the cancer cell of origin of epithelial cancers. They identified the cancer cell of origin and the mechanisms regulating the early steps of tumor initiation in skin basal cell carcinoma, skin squamous cell carcinoma and mammary tumors. His lab developed novel approaches to unravel the mode of tumour growth within their natural environment and to understand the mechanisms regulating cancer stem cell functions. Cédric Blanpain will discuss these different aspects of stem cell biology in his lecture.

Moderator: prof. Elfride De Baere (Department of Biomolecular Medicine, Faculty of Medicine and Health Sciences)

10:00 - Lecture 'Assisted reproductive technology (ART) in humans and animals'

Guest speaker: Prof. Bernard Roelen (Department of Clinical Sciences in Veterinary Medicine, Utrecht University)

While millions of oocytes are formed during the embryonic and fetal development, only a small fraction of these will form a developmentally competent oocyte and be fertilized. Development to  competence relies on an intimate contact between the oocyte and its surrounding somatic cells. Aspects of these oocyte-somatic interactions will be discussed. Furthermore, old and modern techniques that enable fertilization of oocytes outside the body, in a culture dish, will be discussed for both human and animal oocytes.

Moderator: prof. Ann Van Soom (Department of Reproduction, Obstetrics and Herd Health, Faculty of Veterinary Medicine)

14:30 - Lecture 'From bench to bedside: lessons learned from a rare genetic syndrome​'

Guest speaker: Prof. Guillaume Canaud (Institut Necker Enfants Malades, Université de Paris)

CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.

This lecture is a good example of translational research (from bench to bedside) of interest to a broad audience.

Moderator: prof. Lies Lahousse (Department of Bio-analysis, Faculty of Pharmaceutical Sciences)

16:30 - Lecture 'In the shadow of the genome: a challenging journey to the roots of adaptation in Leishmania.'

Guest speaker: prof. Jean-Claude Dujardin (Molecular Parasitology Unit, Institute of Tropical Medicine, Antwerp)

Leishmania is a vector borne parasitic protozoa responsible for leishmaniasis, a major tropical disease endemic in 98 countries worldwide and affecting more than 1 million new individuals each year. The parasite is characterized by strong adaptive skills, which is illustrated among others by its capacity to colonize different types of hosts (vertebrate and invertebrate), infect multiple tissues and easily adapt to drug pressure. Since ten years we are exploring the genomic bases of this adaptability. This endeavour was made possible by a series of technological advances in whole genome sequencing and occurred so far in three steps. First,  we sequenced the genome of 204 clinical isolates of Leishmania donovani (responsible for visceral leishmaniasis, the most severe clinical form) from the Indian subcontinent. This allowed to track the recent history of that population and to highlight events leading to the multiple emergence of antimonial resistance. Furthermore, the study evidenced a dramatic level of variation in gene dosage, both locally and at whole chromosome level, with 33 out of 36 chromosomes showing a variable copy number (somy) in 80% of the isolates. This unprecedented level of aneuploidy would be detrimental in most eukaryotes, but in Leishmania it appears to be part of an adaptive strategy. In a second step, we performed a series of experimental evolution studies and discovered that upon selection of drug resistance in vitro, the first adaptive response of the parasites was a change in the somy of specific chromosomes. This likely occurs in order to increase or decrease the number of transcripts involved in drug resistance. We also found that aneuploidy varied between free culture forms and intracellular parasites obtained from infected animals, suggesting again an adaptive response to changing environment. In a third step, we started a program of single cell genomics to understand the basis of this genomic plasticity. We sequenced the genome of about 1,000 individual cells from a cloned line and were astonished to discover more than 150 different karyotypes in these cells. We found that the karyotypes emerging during resistance selection or in animal experiments were already present among some of the sequenced cells. This aneuploidy mosaicism appears to be a unique strategy allowing Leishmania population to always have cells pre-adapted to changing environment. Implications of our findings and further exploitation will be discussed.   

Moderator: Representative of the student councils StuGG, StuFF and VDK