Scholarships
Conference dedicated exclusively to the topic of VEXAS syndrome
JAAR: 2024
‘The first-ever international convention dedicated exclusively to the topic of VEXAS syndrome, will take plave in Paris, France. VEXAS syndrome is a severe autoinflammatory disorder that was first described in 2020 by Beck et al. The Disorder occurs mostly in men over the age of fifty and is caused by an acquired mutation in the Ubiquitin-like modifier activating enzyme 1 (UBA1) gene in myeloid precursor cells. The result is an upregulation of inflammatory pathways in the bone marrow, causing each patient to have a unique presentation. MDS is one of the most frequently observed characteristics of VEXAS syndrome, and mutations in the UBA1 gene have been included in the genetic panel for MDS at the UMCG. Another frequent manifestation are skin lesions, which most often are diagnosed as Sweet syndrome, a type of the neutrophilic dermatoses associated with acute onset and fever. VEXAS Syndrome has a highly mortality rate and due to the complex mechanisms that cause the systemic inflammation, effective treatment is truly challenging. High-dose corticosteroids, interleukin inhibitors like anakinra and tocilizumab, JAK inhibitors and intravenous immunoglobulin therapy show potential for supressing the inflammation, but most if not all patients eventually become therapy-feractory. The sole curative therapy is allogeneic bone marrow transplantation.’
Conference presentation at The Transplantation Society (TTS) Congress 2024 in Istanbul.
JAAR: 2024
The TTS Congress is a biennial even in which renowned researchers present their most recent and most relevant finding in the field of organ transplantation. The applicant has been submitted an abstract to present her most recent findings in the area of lung transplantation. The aim of the project was to study different approaches to increase the organ pool for lung transplantation, as donor organ shortage is an unceasing issue in the field. It evaluated the influence of ventilation during the period of warm ischemia, right after the circulatory death (donation after circulatory death – DCD), in potential organ donors. After this period, the preservation of graft viability is attainable in a few ways, a recent one being via normothermic regional perfusion (NRP), in which the organ is perfused while still in the donor, decreasing the amount of ischemic injury and the costs related to the donation process. Future steps of the project aim to investigate possible pharmaceutical treatments, such as the 17-β-estradiol and female sex hormones, added to the NRP and/or the already established ex vivo perfusion, in order to avoid further injury or even recondition marginal organs. By attending international congresses, the student is in contact with experienced researchers from all over the world and their group’s work. Given the applicant’s Brazilian nationality, this would be a unique opportunity to discuss her research topic with key researchers in the field of transplantation, engage in activities with her Dutch exchange research group, network, and share knowledge.
A lactate challenge as viability assessment tool during normothermic machine perfusion of human discarded kidneys.
JAAR: 2024
‘The worldwide ongoing organ scarcity problem has resulted in a fundamental change, with the accepted requirements for a kidney donor being expanded to fulfill the need. The next significant issue in the area of transplantation today is effective pre-transplant organ viability assessment of those kidneys. Normothermic machine perfusion (NMP) serves as a platform to assess viability of donor kidneys. NMP is gaining popularity, with several transplant facilities adopting their own NMP protocols and kidney viability criteria. However, there are no distinctive on-pump viability markers or criteria yet that could predict transplant outcomes. This research focusses on using lactate as a marker for renal metabolic function. A kidney is fully metabolic active during NMP, which gives the opportunity to test the metabolic function. Especially lactate metabolism is of great interest as is it correlated to transplantation outcomes. Therefore, the aim of this study is to investigate whether a lactate challenge can serve as a marker of renal metabolic function during NMP.’
Congres presentatie op Society on Thrombosis and Haemostasis Congres
JAAR: 2023
Het glycoproteïne von Willebrandfactor (VWF) wordt door het endotheel gesecreerd bij stimulatie door verschillende prikkels (waaronder hypoxie, cytokines, trombine). Verhoogde niveaus van VWF kunnen duiden op endotheelactivatie of -disfunctie. In patiënten met cirrose zijn de niveaus van VWF in het bloed niet alleen verhoogd, maar is er ook een duidelijke relatie tussen VWF en ernst van de ziekte. Pionierstudies hebben aangetoond dat er niet alleen een correlatie bestaat tussen VWF en het optreden van door portale hypertensie veroorzaakte gebeurtenissen (zoals varicesbloedingen), maar dat verhoogde niveaus van VWF ook geassocieerd zijn met een verhoogde mortaliteit bij patiënten met gedecompenseerde cirrose. Er is echter weinig bekend over de waarde van VWF als voorspeller van mortaliteit bij ernstig zieke patiënten met acute-on-chronic liver failure (ACLF). In onze studie hebben we daarom VWF-niveaus gemeten in een groot aantal patiënten met gedecompenseerde cirrose en ACLF, en deze gecorreleerd met andere laboratoriumparameters en voorspellingsmodellen voor mortaliteit. VWF was inderdaad onafhankelijk geassocieerd met mortaliteit en correleerde nauw met andere voorspellingsmodellen. Bij patiënten met ACLF was de voorspellende waarde van VWF zelfs vergelijkbaar met die van klinisch gebruikte voorspellingsmodellen zoals de MELD-score en CLIF-C-ACLF-score. Deze resultaten suggereren dat VWF mogelijk een toegevoegde waarde zou hebben als een laboratoriummarker voor prognose en mogelijk zou kunnen helpen bij klinische besluitvorming bij ernstig zieke patiënten met leverziekte. Met behulp van het Tekke Huizinga Fonds hebben we onze resultaten kunnen presenteren op het International Society on Thrombosis and Haemostasis Congress 2023, een toonaangevend congres waarbij specialisten op het gebied van trombose, hemostase en vasculaire biologie samenkomen om de nieuwste doorbraken te presenteren.
Scholarship mass spectrometry group of prof. Benedikt Kessler at the University of Oxford
JAAR: 2022
Normothermic machine perfusion (NMP) is a state-of-the-art preservation, resuscitation, and assessment technique for donor organs. However, renal NMP is only scarcely implemented in the clinics because we have yet to unravel the exact metabolic needs of an isolated kidney, nor do we know what “good” ex vivo kidney function actually entails. Therefore, research into the underlying molecular processes of ex vivo NMP of donor kidneys is fundamental before implementing NMP as standard clinical care during kidney transplantation. One approach to mapping out these processes is using proteomic technologies. Using the Tekke Huizinga study scholarship, I paid a visit to the mass spectrometry group of prof. Benedikt Kessler at the University of Oxford. During my visit, I analysed 360 kidney biopsies obtained in vivo and during ex vivo perfusion. The results reveal a clear difference between the in vivo and ex vivo proteome, and are currently further analysed
Study visit King’s College Hospital London
JAAR: 2022
Poortader trombose komt weinig voor in de algemene populatie, maar komt relatief vaak voor bij patiënten met chronische leverziekte en kan bijvoorbeeld complicaties geven bij levertransplantatie. De exacte pathofysiologie van poortader trombose is niet geheel bekend. In eerdere studies lieten we zien dat poortader trombose bestaat uit vaatwand verdikking met een fibrine-rijk stolsel in maar 30% van de gevallen. Op basis van daarvan stelden we de hypothese dat poortader trombose een gevolg is van portale hypertensie-gerelateerde veranderingen in de bloedstroom en vaatwand in de poortader. Deze hypothese gaan we onderzoeken door in een groot cohort van patiënten met chronische leverziekte de dikte van de poortader vaatwand te meten. Dit weefsel is afgenomen en opgeslagen tijdens levertransplantatie. De dikte van de vaatwand wordt gerelateerd aan klinische parameters, waaronder ernst en duur van ziekte, factoren die te maken hebben met portale hypertensie en aanwezigheid van ontsteking en infecties. Met de resultaten hopen we meer inzicht te krijgen in de pathofysiologie van poortadertrombose en in de toekomst betere preventie en (farmacotherapeutische) therapie in te kunnen zetten.
Scholarship University of São Paulo (USP), InCor (Heart Institute), Brazil
JAAR: 2022
As part of my PhD, I will conduct an in vivo study with our collaborators of the University of São Paulo (USP), InCor (Heart Institute), Brazil. These synergistic collaborations are based on the extensive animal experimental expertise in Brazil combined with our knowledge of hydrogels and regenerative medicine. The current pre-clinical trial is a continuation of the in vitro research which I am currently performing in the UMCG. In my research I use an innovative stem cell-based approach in which the adipose stem cell-derived secretome-loaded extracellular matrix-derived (ECM) hydrogel is used as a slow-delivery scaffold for therapeutic factors to alleviate myocardial damage. In rats, these secretome-loaded hydrogels will be administered subpericardially, and the cardiac function and histology compared to controls. This potentially clinically relevant application has not yet been studied or published by other research groups.
Study Visit Tokio
JAAR: 2021
Study visit 2 labs in Tokyo improving skills stem cell technologies.
Research internship Calgary, Canada
JAAR: 2022
Research internship in the Jenne lab at the University of Calgary, Canada that specializes in intravital microscopy, especially in mouse models. This technique enables the study of disease, (micro)perfusion of organs, and the direct effect of medications in living animals. I will learn this imaging technique and study the role of activation of coagulation and neutrophil extracellular trap formation in acute liver failure.
Study visit Aarhus, Denmark kidney transplantation
JAAR: 2021
Study visit University of Colorado Anschutz Medical Campus, USA
JAAR: 2020
For this project, we will develop reagents and methods for PET-based molecular imaging of tissue-bound complement activation fragments. In vivo imaging of complement could be useful in transplantation to diagnose and monitor antibody-mediated rejection. (University of Colorado Anschutz Medical Campus, USA).
Study visit University of Massachusetts Medical School, USA
JAAR: 2022
High end research on RNA interference (RNAi)Het gesubsidieerde project omvat een samenwerking tussen het transplantatie-onderzoek lab van dr. Martins en het RNA Therapeutics Insititute van prof. Khvorova waar baanbrekend onderzoek naar RNA-interferentie (RNAi) wordt gedaan aan de University of Massachusetts Medical School in Amerika. RNAi is een natuurlijk verschijnsel waarbij dubbelstrengs RNA-moleculen vooraf geselecteerde genen kunnen stilleggen met dezelfde code. RNAi heeft recent aandacht gekregen op het gebied van orgaantransplantatie om genen gerelateerd aan ischemie-reperfusie schade stil te leggen. Met dit project willen we onderzoeken of RNAi tijdens machine perfusie van donorlevers een belangrijk ischemie-reperfusie gen kan uitschakelen (de apoptose-receptor FAS). We verwachten dat de behandeling met RNAi gericht tegen FAS het orgaan minder kwetsbaar maakt voor ischemische schade en daarmee de leverfunctie na transplantatie verbeterd. In de toekomst zouden zo meer organen van suboptimale kwaliteit kunnen worden getransplanteerd om zo de sterfte op de transplantatie-wachtlijst te verminderen.
Study visit on Renal transplantation at the University Hospital in Oslo
JAAR: 2019
Study visit King’s College Hospital London,
JAAR: 2019
Study visit on prospective cohort study on the effects of prohemostatic interventions on hemostatic status of patients with liver disease in a real-life setting.
Internship clinical physician observer at the Bone Marrow Transplantation Unit
JAAR: 2019
Spending time as a clinical physician observer at the Bone Marrow Transplantation Unit of the Fred Hutchinson Cancer Research Center at the Seattle Cancer Care Alliance, Seattle, USA
Research internship at King’s College London
JAAR: 2019
Research internship on haemostasis in patients with cirrhosis that receive pre-operative transfusion of Fresh Frozen Plasma or platelets at King’s College London
Visit conference American Thoracic Society Annual Scientific Conference in San Diego
JAAR: 2018
Research internship on hemostasis
JAAR: 2018
Research internship on hemostasis in patients undergoing hepatobiliary surgery at the Liver Institute at King’s College Hospital, London U.K.
Study visit First Affiliated Hospital of Sun Yat-Sen, Guangzhou, China
JAAR: 2018
Research Project Great Ormond Street Hospital London
JAAR: 2017
Investigate the role of low perfusion and low oxygenation of the intestine in the pathogenesis of NEC (Necrotic Enterocolitis) and I will investigate if AFS (Amniotic Fluid Stem cells ) cells protect the intestine of ischemia by altering the microcirculation.
Study visit Oxford
JAAR: 2017
With the use of proteomics, we would like to see how the protein profile of kidneys is altered by the hypothermic machine preservation. Furthermore, we would like to see if we can use proteomics to evaluate other preservation and regeneration techniques, studied for the use of kidneys between donation and transplantation.
Study visit Harvard, USA
JAAR: 2016
Progressive renal failure in transplant patients is associated with a highly unexplained pro-inflammatory condition which contributes to increased morbidity and mortality in the renal patient group.
Research scholarship Virginia Commonwealth University, USA
JAAR: 2014
Research internship on hemostatis in patients with fatty liver disease
Study visit International Liver Transplantation Society
JAAR: 2014
Stem Cells and Cancer Keystone Meeting, Banff, Canada
JAAR: 2014
Clinical Elective in Hematology, Cambridge
JAAR: 2013
London Research Institute
JAAR: 2012
ISTH Kyoto
JAAR: 2011