项目介绍

2024年5月5日

TARGID, the translational research center for gastrointestinal disorders, is one of the largest research groups in KULeuven Biomedical Sciences and is a leading gastrointestinal research center on a global level. The Gastrointestinal Motility and Sensitivity Research group focuses on research in patients and healthy controls, to understand the pathophysiology, impact and treatment of chronic gastrointestinal symptoms, as present in patients with Disorders of Gut-Brain Interaction. This comprises the irritable bowel syndrome and functional dyspepsia, as well as gastroparesis and many similar highly prevalent conditions. The group is led by Prof. J. Tack and comprises 15 to 20 researchers from varied backgrounds. Dr. Florencia Carbone is a research leader in the group and Dr. Karen Van den Houte is a postdoctoral researcher. Given the international composition of the group, the language for daily interactions is mostly English.

Website van de eenheid

Project

The Gastrointestinal Motility and Sensitivity Group at the University of Leuven (KU Leuven, Belgium) is looking for a highly motivated PhD student to unravel the cellular and molecular mechanisms underlying food reactivity and response to dietary and anti-inflammatory therapy in patients with Functional Dyspepsia (FD).

FD affects 7.2% of the adult population and has a significant impact on quality of life. Patients present with recurrent symptoms in the stomach region, but routine investigations including endoscopy are macroscopically normal. Recent studies have shown low-grade duodenal inflammation characterized by influx of activated eosinophils and mast cells and impaired mucosal barrier function in FD. We hypothesize that symptoms are triggered by specific food allergens which, in the presence of impaired mucosal barrier, activate mast cells and eosinophils. Two ongoing pivotal trials are investigating this hypothesis. In a placebo-controlled trial, we are investigating the effects of the endogenous mast cell stabilizing agent palmitoylethanolamide on symptoms and duodenal mucosal alterations in FD patients. In a sham-controlled dietary elimination trial in patients without classical IgE-mediated food alleriges, we are studying the effect of elimination of trigger nutrients, identified by duodenal confocal laser endomicroscopic evaluation of atypical food allergies, on symptoms and duodenal mucosal alterations in FD patients. In all patients, duodenal biopsies and serum samples for various assessments were obtained at baseline and at the end of medical or dietary therapy. In addition, comparator samples are available from healthy controls.

The PhD fellow will be involved in sample collection and some logistics for the studies, which are run by a clinically focused PhD fellow. The aim of your part of the project is to use these samples and ongoing and follow-up in vivo studies to understand:

1) The molecular basis of the alterations of integrity of the duodenal mucosa in FD patients and its evolution during medical and dietary therapy.

2) The characterisation of the cellular inflammatory infiltrate in FD patients and its evolution during medical and dietary therapy.

3) The pathway through which IgE-negative patients display acute atypical allergic reactions to food components as evaluated by duodenal confocal endomicroscopic studies. Both mast cell targeting as eosinophil targeting mechanisms will be considered.

The hypothesis focuses on non-IgE mediated mast cell activation, through for instance MRGPRX2 receptor activation.

4) The findings in the palmitoylethanolamide study will be correlated with tissue levels of palmitoylethanolamide and their correlation with markers of mast cell activation and response to therapy.

5) There is a potential to correlate mechanistic observations to a genetics database.

Key references:

1. Sperber A, Bangdiwala SI, Drossman DA, Ghoshal UC, Simren M, Tack J, Whitehead W, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome

Foundation Global Study. Gastroenterology 2021;160: 99-114.

2. Sarnelli G, Pesce M, Seguella L, Lu J, Efficie E, Tack J, De Palma FDE, D’Alessandro A and Esposito G. Impaired Duodenal Palmitoylethanolamide Release Underlies Acid-Induced Mast Cell

Activation in Functional Dyspepsia. Cell Mol Gastroenterol Hepatol. 2020; 11: 841-855.

3. Fritscher-Ravens A, Schuppan D, Ellrichmann M, Schoch S, Rocken C, Brasch J, Bethge J, Bottner M, Klose J and Milla PJ.. Confocal endomicroscopy shows food-associated changes in the

intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology 2014;147.4. Van den Houte K, Bercik P, Simren M, Tack J, Vanner S. Mechanisms underlying food-triggered symptoms in disorders of gut-brain interactions. Am J Gastroenterol. 2022 Jun 1;117(6):937-946

5. Schol J et al. Role of atypical food allergies in functional dyspepsia: evaluation by six food elimination diet and confocal laser endomicroscopy food allergy testing. Gastroenterology

2022; 162: S926.

6. Giancola F, Volta U, Repossi R, Latorre R, Beeckmans D, Carbone F, Van den Houte K, Bianco F, Bonora E, Gori A, Costanzini A, Boschetti E, Caio G, Vanuytsel T, Stanghellini V, Tack J and De

GIiorgio R. Mast cell-nerve interactions correlate with bloating and abdominal pain severity in patients with non-celiac gluten / wheat sensitivity. Neurogastroenterol Motil. 2020; 32: e13814.

Profiel

• You hold a Master’s degree in Biomedical Sciences, Bioengineering, Biotechnology, or a related discipline.
• Hands-on experience with biochemical assays such as Western blot and qRT-PCR analysis, FISH, cell culture, immunohistochemistry, etc. is a strength. 
• You have a strongh scientific curiosity, are motivated for research, can cope with the need for problem solving as research evolves, and display great precision in your work. You are able to function independently as well as in team. You can interact with patients and patient sample collection. 
• You have excellent oral and written communication skills in English.

Aanbod

• We offer a PhD position in a dynamic and enthousiastic team with large international impact using state-of-the-art technologies and settings.
• We support PhD students with close guidance and provide ample opportunity to participate in (inter)national collaborations and conferences. 
• We aspire to create an open minded lab culture where members are welcomed regardless of age, race, gender, cultural background, or limitations.
• The KU Leuven has a strong international character and is located in Leuven, close to Brussels at the heart of Europe.

Interesse

For more information, contact prof. dr. Jan Tack, tel.: +32 16 37 74 74, mail: jan.tack@kuleuven.be or Dr. Maria Florencia Carbone, mail: florencia.carbone@uzleuven.beSolliciteren voor deze vacature kan tot en met 05/07/2024 via onze online sollicitatietoepassing

KU Leuven wil een inclusieve, respectvolle en sociaal veilige gemeenschap zijn. Wij omarmen diversiteit tussen individuen en groepen als een meerwaarde. Open dialoog en verschillen in perspectief zijn noodzakelijk in een ambitieuze onderzoeks- en onderwijsomgeving. In ons streven naar gelijke kansen erkennen wij de gevolgen van historische ongelijkheden. Wij aanvaarden geen enkele vorm van discriminatie op basis van, onder meer, geslacht, genderidentiteit en -expressie, seksuele oriëntatie, leeftijd, etnische of nationale afkomst, huidskleur, levensbeschouwelijke overtuiging, neurodivergentie, arbeidshandicap, gezondheid, of socio-economische status. Bij vragen over toegankelijkheid of aangeboden ondersteuning helpen we je graag op dit e-mailadres.

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Heb je een vraag over de online sollicitatieprocedure? Raadpleeg onze veelgestelde vragen of stuur een e-mail naar solliciteren@kuleuven.be