Becoming a Scientist
Virus Fighter
Build a virus or fight a pandemic!
Maya's Marvellous Medicine
Battle Robots of the Blood
Just for Kids! All about Coronavirus
Saturday, February 23, 2019 at 10:46AM 
Sad to see John Barber leaving us to go back to his medical degree. He has spent the last year uncovering a novel genetic cause of neutropenia - details to follow soon!
Best of luck John, you'll be missed!
Liston lab Friday, February 8, 2019 at 10:15PM 
Congratulations to Dr Stéphanie Humblet-Baron, who was just awarded the prestigious (and highly competitive) BOF-ZAP award. With this award Stéphanie starts a tenure-track research professorship and her own independent group.
The success of both Prof Humblet-Baron and Prof Schlenner at the BOF-ZAP awards puts the Translational Immunology laboratory in a great position. Going forward from my move to the Babraham, Prof Schlenner is leading the mouse immunology research and Prof Humblet-Baron is leading the clinical immunology research program.
Leaving two such talented and determined women to take over my lab, and push it to new heights, is my proudest legacy of 10 years in Leuven.
The Humblet-Baron team will develop and use cutting-edge systems immunology approach to study the many diseases in which the immune system places a key role, from primary immunodeficiency to infections to cancer to neurodegeneration. Watch out for great things new Prof Humblet-Baron is here!
Thursday, January 24, 2019 at 10:00AM Identical twin girls who presented with severe arthritis helped scientists to identify the first gene mutation that can single-handedly cause a juvenile form of this inflammatory joint disease. By investigating the DNA of individual blood cells of both children and then modelling the genetic defect in a mouse model, the research team led by Adrian Liston (VIB-KU Leuven) was able to unravel the disease mechanism. The findings will help to develop an appropriate treatment as well.
Juvenile idiopathic arthritis is the most common form of all childhood rheumatic diseases. It is defined as arthritis that starts at a young age and persists throughout adulthood, but which does not have a defined cause. Patients present with a highly variable clinical picture, and scientists have long suspected that different combinations of specific genetic susceptibilities and environmental triggers drive the disease.
A single gene mutation
In a new study by researchers at VIB, KU Leuven and UZ Leuven, the cause of juvenile arthritis in a young pair of identical twins was traced back to a single genetic mutation.
"Single-cell sequencing let us track what was going wrong in every cell type in the twin’s blood, creating a link from genetic mutation to disease onset,” explains Dr. Stephanie Humblet-Baron, one of the researchers involved in the study. “It was the combination of next generation genetics and immunology approaches that allowed us to find out why these patients were developing arthritis at such a young age.”
Of mice and men
Parallel studies in mice confirmed that the gene defect found in the patients’ blood cells indeed led to an enhanced susceptibility to arthritis. Prof. Susan Schlenner, first author of the study, stresses the relevance of this approach: "New genetic editing approaches bring mouse research much closer to the patient. We can now rapidly produce new mouse models that reproduce human mutations in mice, allowing us to model the disease of individual patients."
According to immunology prof. Adrian Liston such insights prove invaluable in biomedical research: “Understanding the cause of the disease unlocks the key to treating the patient.”
From cause to cure
Liston’s team collaborated closely with prof. Carine Wouters, who coordinated the clinical aspect of the research: "The identification of a single gene that can cause juvenile idiopathic arthritis is an important milestone. A parallel mouse model with the same genetic mutation is a great tool to dissect the disease mechanism in more detail and to develop more effective targeted therapies for this condition.”
And the little patients? They are relieved to know that scientists found the cause of their symptoms: "We are delighted to know that an explanation has been found for our illness and more so because we are sure it will help other children."
Thankfully, the children’s arthritis is under good control at the moment. Thanks to the new scientific findings, their doctors will be in a much better position to treat any future flare-ups.
NFIL3 mutations alter immune homeostasis and sensitise for arthritis pathology
Schlenner et al. 2018 Annals of the Reumatic Diseases
Liston lab, Medicine, immunology Thursday, December 20, 2018 at 4:59PM In two recent studies, the same team of scientists has uncovered the mechanisms underlying two distinct immunological disorders affecting both children and adults. Stephanie Humblet-Baron(VIB-KU Leuven) was the researcher at the helm of both projects.
A pediatrician by training, Stephanie Humblet-Baron is building a career unravelling immunological disorders that affect children. She divides her time between the clinic and the lab, where she is a senior team leader in the lab of Adrian Liston (VIB-KU Leuven).
From disease to biology and back again
Ever since the start of her medical training, Humblet-Baron developed a special interest in unraveling the biological mechanisms that cause immunological problems. Many immune diseases are poorly understood, and this lack of knowledge also limits treatment options and choices.
“People sometimes refer to these diseases as rare,” says Humblet-Baron, “but we all carry risk factors for many immunological diseases. Even if a given mutation is rare, the accumulated variation in immunological responses affect a broad set of outcomes, for example how someone responds to cancer treatment or drugs for cardiovascular conditions. That is why understanding the mechanisms underlying immune-dysregulation is so important.”
In her most recent work, Humblet-Baron, together with her colleagues in the lab of Adrian Liston (VIB-KU Leuven), focused on the mechanisms causing myeloproliferative disease and hemophagocytic lymphohistiocytosis, two diseases that are fatal unless given aggressive treatment.
Myeloproliferative disorder: a partner in crime for dendritic cells
Dendritic cells are specialized antigen-presenting cells that play a crucial role in coordinating innate and adaptive immune responses. In both patients and mice, depletion of dendritic cells leads to myeloproliferative disorder, but how or why—no one really knew.
“To understand what was going wrong, we created a mouse model where dendritic cells were present in normal numbers, but were functionally impaired,” explains Humblet-Baron. “We found that without the antigen-presenting capacity of dendritic cells, the mice developed myeloproliferative disorder.”
The team uncovered that it was not the number of dendritic cells, but their partnership with CD4 T cells of the immune system that was crucial for disease development. When CD4 T cells were absent as well, the mice showed no symptoms of myeloproliferative disease.
This has important implications for patients, where specific mutations also manifest both dendritic cell deficiency and myeloproliferative disorder. “Based on the original model disease model, the proposed line of treatment would be dendritic cell replacement, currently only possible through bone-marrow transplantation,” says prof. Adrian Liston. “But these new results indicate that attenuating the activatory signal from CD4 T cells could also reduce the development of myeloproliferative disorder.”
Hemophagocytic lymphohistiocytosis: New light on a deadly disease
Hemophagocytic lymphohistiocytosis, HLH for short, is a severe disease less than 2 out of 3 patients survive. It can be triggered by a variety of factors, including genetic defects, viral infections, anti-tumor responses or unchecked autoimmunity. Excessive production of interferon γ was assumed to be the key pathological step, but based on patient evidence and a pre-clinical mouse model of the disease, the Leuven research team has now found that there is much more to it.
Humblet-Baron: “We found that the production of interferon γ was only responsible for part of the features of the disease. Excessive consumption of the immune signaling molecule interleukin 2 by hyperactivated CD8 T cells, the suppressor cells of our immune system, had a much greater impact on the inflammation.”
This means that at least two different disease pathways are at play—knowledge that indicates that we could save the lives of more patients if we also targeted both pathways during treatment.
“This study not only provides a new paradigm for understanding HLH, with major implications for its treatment, but also gives us a broad insight into how hyperactivated CD8 T cells cause damage,” adds prof. Adrian Liston.
“We can learn so much from an in-depth analysis of the immune cells present in a simple sample of blood from patients,” concludes Humblet-Baron, who hopes to uncover the mechanisms underlying many more of these immunological problems. “Coupled with the power of biochemical and animal research, these insights are really changing how we diagnose and treat patients in the clinic.”
—
Humblet-Baron, et al 2018 Blood. "Murine myeloproliferative disorder as a consequence of impaired collaboration between dendritic cells and CD4 T cells"
Humblet-Baron et al. 2018 Journal of Allergy and Clinical Immunology. "IFN-γ and CD25 drive distinct pathological features during CD8 T cell hyperactivation in hemophagocytic lymphohistiocytosis"
Liston lab, Medicine, women in science Tuesday, December 11, 2018 at 10:40AM 
Congratulations to Steffie Junius, the first PhD student to win the Golden Pipette!
Dr Carly Whyte had to relucantly hand over the Golden Pipette to Steffie Junius, in recognition of her pioneering experiments on regulatory T cell fate-mapping.
This means the Golden Pipette will stay in Leuven for now, but the Babraham Team is building up to take back the pipette in 2019!
Wednesday, November 28, 2018 at 8:48PM Congratulations to Prof Susan Schlenner who secured FWO funding today for a four year project on regulatory T cells! FWO is highly competitive and it is very rare for an applicant to be successfully funded on their first independent application. A sign of future success!
Liston lab, women in science Thursday, November 8, 2018 at 5:43PM Liston lab 
