Research Fellowships

Supervisor: Lydia Visser MD PhD, working with three PhD-students with an MSc

Field of research: Pathology and Medical biology

Description: We will look at different aspects of lymphoma research by looking at the expression of proteins, drug sensitivity, combination therapy, or effect on the microenvironment. We can use techniques such as immunohistochemistry, cell culture, flowcytometry, western blot, elisa and metabolic assays. There will be different projects.

Experience from student: Looking for a student with interest in labwork.

Supervisor: Sebo Withoff, PhD 

Field of research: Genetics ERIBA

Description: The Immunogenetics group of the Department of Genetics within the UMCG investigates the role of genetic variation in health and the aetiology of autoimmune diseases (e.g. coeliac disease), the role of the gut microbiome therein, and is generating iPSC-based organ-on-chip models to investigate and validate ‘omics’ findings.  

The data for these studies are mostly generated by next generation sequencing such as single-cell RNA-seq and ATAC-seq. The generation and analyses of the data requires a broad range of scientific expertise. In our group, a dynamic and highly interactive environment is created in which bioinformaticians, geneticists, statisticians, molecular biologists, stem cell biologists and immunologists work closely together.  

Important findings published by the group are (a) the shared genetics of autoimmune diseases, (b) 95% of the autoimmune disease-associated single nucleotide polymorphisms (SNPs) affect gene expression rather than gene function, (c) eQTL effects of GWAS SNPs on long non-coding RNAs (lncRNAs), and (d) a range of environmental factors affecting the human microbiome.  

The current ongoing research is for a large part focused on the prioritisation of SNPs, genes, pathways and cell types affected in autoimmune diseases, on in vitro experiments to validate the function of the prioritised candidates and on determining how host genetics affects microbiome composition.  

Depending on the background and your interests, we will design a working plan for the two-week internship.  

Experience from student: Looking for a student with interest in lab work. 

Supervisor: Prof. Gea Holtman, PhD

Field of research: Medicine general and internal   

Description: Patients with long-term conditions (e.g., kidney disease, type 2 diabetes mellitus, hypertension) have regular monitoring appointments, including blood tests, according to guidelines. However, substantial variation in adherence to these guidelines persists in clinical practice. Developing flowcharts for general practitioners on which tests should be performed and when, which could be used in routine practice and provide benchmarks, may help reduce this variation. The aim of this project is to develop flowcharts based on primary care guidelines.

Experience from student: Experience with quantitative data analysis, preferably with R.

Supervisor: Prof. Hélder Santos, PhD

Field of research: Biomedical technology & immunotherapy 

Description: This project will involve the optimization of hydrogel composition, sophisticated particle fabrication, and drug-loading strategies to achieve optimal therapeutic efficacy and biocompatibility. In vitro studies will evaluate the release kinetics, cytotoxicity, and targeting efficiency of the hydrogel-loaded PPs using GB cell lines and primary brain cell cultures. Subsequently, organoids testing and experiments in 3D glioblastoma models or equivalent systems will assess the therapeutic efficacy, tumour-targeting specificity, and biodegradability of the developed system.

Experience from student: Preference is given to a student with a background in chemistry, biomedical engineering, cell biology, or pharmacy

Patient material handling: No

Supervisor: Prof. Hélder Santos, PhD

Field of research: Biomedical technology & immunotherapy  

Description: This project will explore the design of nanoscale drug delivery systems capable of homing to injured cardiac tissue active targeting mechanisms, using cell-based components to build nanoparticles using microfluidics technology. These nanomedicines will be engineered to deliver therapeutic agents that modulate inflammation, promote angiogenesis, and support tissue regeneration. In vitro characterization and 3D-models and iPSCs will be used to assess nanoparticle physicochemical properties, targeting efficiency, and biological performance.

Experience from student: Preference is given to a student with a background in chemistry, biomedical engineering, cell biology, or pharmacy

Supervisor: Prof. Esther Metting, PhD

Field of research: Data Science

Description: In this internship, the student explores the central question: Can companion robots help reduce feelings of loneliness, and under what conditions do they support or hinder well-being? The project combines scientific literature research with hands-on experimentation and personal experience, following a reflective and exploratory approach.

The internship starts with a structured literature review (e.g. scoping or narrative review) on the use of companion and social robots to address loneliness. The student investigates how robots are currently used across different contexts and populations, such as students, older adults, or people living alone. Attention is paid to proposed mechanisms of action (e.g. social presence, daily structure, emotional support), as well as ethical and societal concerns, including dependency, privacy, and the risk of replacing human contact. Based on the literature, the student formulates initial design assumptions and hypotheses about what makes a companion robot supportive in daily life.

Next, the student works hands-on with a robot, programming and iteratively refining an interaction algorithm intended for everyday use by the student themselves. Possible functions include short conversations or check-ins, reminders, encouragement of social or physical activities, mood reflection, and adaptive responses based on user input. The student uses the robot in their own daily life for a defined period and systematically documents their experiences.

A key element of the project is experiential reflection. The student keeps an experience log or diary, describing usage moments, emotional responses, perceived effects on loneliness and well-being, and moments of discomfort or resistance. Based on both the literature and these personal experiences, the student continuously adjusts the robot’s algorithm, critically evaluating which assumptions hold and which do not.

The internship concludes with an experience-based report, in which the student reflects on their personal journey, links insights to scientific literature, and formulates recommendations for the design and use of companion robots. This internship can be carried out individually or in pairs, allowing students to compare experiences and design choices

Experience from student:  Some experience with programming e.g. 

Supervisors: Prof. Romana Schirhagl, PhD & Prof. Marina Volkova PhD

Field of research: biomedical engineering

Description: Fluorescent nanodiamonds (FNDs) are nanoparticles successfully used for intracellular quantum sensing to detect free radicals, which are known to take a crucial part in many cellular processes. Since FNDs are resistant to photobleaching, it allows for them to be used in the real-time assessment of cell health by free radical quantification. We aim to investigate if FNDs can be used as an extracellular biosensors to assess the health of bioreactor-grown Saccharomyces cerevisiae yeast cultures.

Experience from student: Practical lab experience

Supervisors: Dr. J. van den Born PhD, Prof. Dr. S.P. Berger, PhD.  

Field of research: Nephrology

Description: In Nephrology Dept. various projects are running using diverse methodologies (see 1-4). You are invited to express your interests in one of these fields (being either clinical, epidemiological, human- or animal in vivo- or in vitro experimental) to indicate what sub-project interests you most. Please motivate your interest for the specific topic.

1. Antibody-mediated rejection of transplanted kidneys. Within this research line we try to unravel the role of the immune system in chronic renal damage in transplanted kidneys, mostly by antibody-mediated rejection. In an in vitro model using immortalized renal endothelial cells we measure cell death by donor-specific antibodies, NK-cells and/or complement. Results will be associated to clinical outcome parameters.
2. Our center has a large population of renal transplant recipients. These patients are monitored very closely, and regimens aimed at increasing the duration of graft function as well as patient survival are being studied currently. A large database including biobanked urine and plasma is available in TransplantLines. In new trials we work on personalized immunosuppression. Within these cohorts we try to entangle which factors associate/contribute to transplant loss and mortality.
3. General population cohorts are studied to detect which parameters lead to initiation of progressive renal function loss and its complications. The cohorts PREVEND and Lifelines from the general population are good examples. The natural course is followed to study possible causes of morbidity and mortality in relation to renal parameters.
4. Endothelial dysfunction highly contributes to progression of renal and cardiovascular diseases. We are interested in the effects of heavy metals such as cadmium and/or transplantation conditions on the endothelial glycocalyx, and functional consequences of endothelial injury. This work is performed on human (renal) endothelial cells in culture and tissues from experimental animals and renal patients.

Experience from student: Practical lab experience

Supervisor: Dr. Janine K. Kruit, PhD

Field of research: Pediatrics

Background: Optimal maternal health and nutrition status are important for fetal growth and development and sets the stage for future health and disease risk. Currently, however, in many countries more than half of women are overweight or obese when becoming pregnant. Maternal obesity is the main risk factor for the development of gestational diabetes mellitus (GDM), which affects approximately 15% of pregnancies. Diabetic pregnancies not only carry a higher risk for further complications such as fetal macrosomia, preeclampsia and stillbirth, but children born to such pregnancies are at increased risk of poor metabolic health, including a 7-fold increased risk for type 2 diabetes (T2D). In order to understand this increased risk for T2D in the offspring, we developed a preclinical mouse model of GDM. Offspring of GDM mice showed impaired glucose tolerance, indicating disturbances in glucose control. In this project, we will study the impact of GDM on the development and function of metabolic relevant organs, such as fat, liver, intestine and pancreas.

Work description: To determine the effect of GDM on endocrine pancreas development, we performed RNA sequencing on islet samples. Currently, we are confirming these changes in gene expression on histological samples using pancreatic tissue material. You will contribute to this research by performing immunofluorescent or immunohistochemical staining for proteins for example involved in beta-cell proliferation, apoptosis or dedifferentiation.

Experience from student: Interest in lab work

Supervisors: Prof. Priya Vart, PhD

Field of research: Pharmacoepidemiology and Genetics

Description: In the treatment of type 2 diabetes, glucagon-like peptide-1 receptor agonists (GLP1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are among the most effective options for reducing the risk of both chronic kidney disease (CKD) progression and cardiovascular complications. Findings from the recent Evaluate Renal Function with Semaglutide Once Weekly trial suggest that these two drug classes may have complementary benefits and should be considered key components of CKD and cardiovascular disease management. This study aimed to assess real-world prescribing patterns of SGLT2is and GLP1RAs in individuals with type 2 diabetes, stratified by cardiorenal risk categories, based on CKD risk levels and the presence of cardiovascular disease, to determine whether those at the highest risk receive the most intensive treatment.

Experience from student: Experience of some data analysis with any statistical software, preferably, SPSS, Stata or R.

Supervisors: Daily supervisor: Fynn Elvers, MD (PhD-Candidate), 

Head supervisor: Prof. dr. Ton Lisman MD, PhD

Field of research: Experimental Surgery

Description: Hemostasis is the central process leading to blood cessation, consisting of platelet plug formation, coagulation with clot formation, and clot breakdown. Patients with liver disease frequently acquire complex changes in their hemostatic system due to chronic endothelial activation and failure of hepatic protein synthesis. Indeed, plasma levels of various prohemostatic (promoting thrombosis) and antihemostatic proteins (promoting bleeding) are aberrant. The net result of these changes is an unstable hemostatic system. Historically, liver disease was considered a bleeding disorder, however, evidence of the last decade has changed this assumption. Bleeding complications occur seldom and are mostly related to portal hypertension and major procedures, but not inherent coagulation failure. In contrast, evidence suggests that liver disease is frequently characterized by prothrombotic hemostatic abnormalities and associated with an elevated risk of venous thromboembolism. 

Multiple research projects are available. The project of the IRF will be tailored to the laboratory experience of the student(s). During the 2-weeks, you will become familiar with laboratory research on hemostasis in patients with liver disease. This may include techniques such as enzyme-linked immunosorbent assays to determine antigen or activity levels of hemostatic proteins, gel electrophoresis, thrombin generation assays, clotting time assays, or clot lysis time assays. 

Experience from student: Interest in lab work

Group Leader: Prof.dr. Marco Demaria

Direct Supervisor: PhD candidate Francesca Pagliarin

Field of research: Cellular Aging & Senescence

Background: Sex differences play a crucial role in numerous physiological and pathological processes, including aging, cancer, and age-related diseases. Although females generally outlive males and show lower mortality from major conditions, this longevity advantage is paradoxically accompanied by greater frailty and multimorbidity in late life. These patterns suggest that biological aging progresses differently between the sexes and that underlying cellular mechanisms may contribute to this divergence.

Cellular senescence, an irreversible growth-arrest state driven by persistent DNA-damage signaling and the senescence-associated secretory phenotype (SASP), is increasingly recognized as a key contributor to these sex-specific patterns.

Senolytics and senomorphics have emerged as promising strategies to eliminate or modulate senescent cells, delaying the onset of age-related diseases and improving tissue function. However, accumulating evidence indicates that male and female senescent cells respond differently to these interventions, emphasizing the need for personalized, sex-aware strategies. One potential explanation is that pro-survival and anti-apoptotic pathways, which enable senescent cells to resist clearance, may be differentially regulated in male versus female cells, altering their sensitivity to senotherapeutics.

Recent findings from our laboratory demonstrate that female mice accumulate more p16⁺ senescent cells than males as they age. Despite this higher baseline burden, female p16-3MR mice exhibited greater functional improvements following ganciclovir-mediated senescent cell clearance, including enhanced grip strength, improved skin regeneration, and reduced liver damage. These results indicate that both the accumulation of senescent cells and the physiological benefits of their removal are more pronounced in females.

Together, these observations highlight that the biology of aging and the efficacy of anti-aging interventions are deeply sex-dependent. However, the molecular basis underlying the differential responses of male and female senescent cells to senolytics and senomorphics remains unresolved. Clarifying these mechanisms is

essential for developing effective, personalized senotherapeutic strategies capable of improving healthspan in both men and women.

Project Description: It remains unclear why and how female and male senescent cells differently response to senolytics and senomorphics. In this small project, we aim to investigate the potential roles of several pro-survival and anti-apoptotic pathways as modulators of this sex-disparity. The student will employ techniques such as Senescence Associated b-galactosidase staining, Edu proliferation staining, gH2Ax staining, RT-qPCR as well as western blot and MTS assay to assess the impact of these treatments on the cell viability and senescence signature in female and male senescent cells at gene and protein levels.

Experience from student: Practical lab experience is preferred.

Patient material handling: No patient material is included in this project.

Supervisors: Peter J. van der Most, PhD

Field of research: Genetic Epidemiology

Description: The project will be entirely computer-based. Some experience with programming or scripting (particularly R) is desirable, but not necessary. No patient-data or material will be used.

Atherosclerosis is the main pathway leading to coronary artery disease. One of its hallmarks is the calcification of atherosclerotic plaques. This process can be quantified using CT scans, which makes it a viable predictor of cardiovascular risk.

Coronary Arterial Calcification (CAC) is determined by multiple factors, including genetic ones. Recently, we performed a genome-wide association study in the ImaLife cohort (a subcohort of the Lifelines population cohort), where we searched for genes associated with CAC. These genes may help us predict individual risk of CAC, and in turn cardiovascular risk. Also, further understanding of the biological pathways behind CAC may yield clues towards prevention or treatment. This is the objective of the current project.

In this project, the students will perform bio-informatic follow-up of the genes identified in the GWAS. Specifically:

–             What the function is of the genetic variants (and strongly linked variants);

–             The genes where these variants are located, and their function;

–             The pathways these genes belong to;

–             And whether certain pathways are seen more often than expected (gene enrichment).

The eventual goal is to provide a list of genes that should be prioritized for follow-up analyses in the lab.

Methods: R, web tools, unix/linux, slurm

Project type: Computer work

Experience from student: None, but some experience with coding, particularly in R, will be helpful.

Supervisors: Peter J. van der Most, PhD

Field of research: Genetic Epidemiology

Description: The project will be entirely computer-based.  Some experience with programming or scripting (particularly R) is desirable, but not necessary. No patient-data or material will be used.

p-Phenylenediamine (PPD) is one of the most used components in oxidative permanent hair dye, as well as a component in temporary black henna tattoos. It’s also a strong allergic sensitizer. Strangely, despite its popularity, only 4% of European dermatitis patients develop a PPD contact allergy. Susceptibility to PPD is influenced by genetics, but underlying genes are only partially known. 

Recently, we performed a genome-wide association study to look for genes associated with PPD contact allergy. Identifying these genes may help us understand the biology behind contact allergy.

Students will perform bio-informatic follow-up of the genes identified in the GWAS, to determine their function and relationship to other genes. Specifically:

–             The function of these genetic variants (and strongly linked variants);

–             The genes they are located in;

–             The function of these genes; and the pathways they belong to;

–             And whether certain pathways are seen more often than expected (gene enrichment).

The goal is to provide a list of genes that should be prioritized for follow-up analyses in the lab.

Methods: R, web tools, unix/linux, slurm

Project type: Computer work

Experience from student: None, but some experience with coding, particularly in R, will be helpful.

Supervisors: Paola Mian PharmD, PhD

Field of research: pharmacology/pharmacology & toxicology

Description: Medication use during pregnancy is common, as many women require continued pharmacotherapy for chronic or acute conditions to maintain maternal health. However, physiological changes during pregnancy and the presence of the placenta complicate the prediction of fetal drug exposure. The placenta plays a central role in regulating the transfer of drugs between the maternal and fetal circulation, through processes such as passive diffusion, active transport, binding, and metabolism. A limited understanding of these mechanisms contributes to uncertainty regarding fetal safety and hampers evidence-based dosing recommendations for pregnant women.

In this project, students will investigate ex vivo human placental perfusion models as an experimental approach to study placental drug transfer. These models allow controlled investigation of drug transfer across the human placenta by simultaneously perfusing the maternal and fetal sides of an isolated placental cotyledon. Ex vivo perfusion studies provide quantitative data on concentration-time profiles, transfer rates, placental tissue accumulation, and, in some cases, placental metabolism, thereby offering direct insight into fetal exposure without in vivo experimentation.

The first part of the project consists of a structured literature review of ex vivo placental perfusion studies. Students will evaluate different perfusion model designs and experimental conditions, and assess how these influence reported measures of placental drug transfer.

In the second part, students will focus on translating ex vivo perfusion data into inputs for physiologically-based pharmacokinetic (PBPK) models describing maternal-placental–fetal drug disposition. They will identify which types of ex vivo data are required to parameterize and evaluate placental PBPK models and distinguish essential from supportive data elements.

The goal of the project is to understand how ex vivo placental perfusion data can be used to support the development of mechanistic PBPK models that enable evidence-based dosing strategies during pregnancy, ensuring effective treatment for the mother while minimizing risks to the fetus.

Experience from student: Students should be interested in perinatal pharmacology and the use of pharmacokinetic models.

Supervisors: DJ Mulder, MD, PhD en Jesse Cappelle, PhD student

Field of research: Clinical Geriatrics / Internal Medicine of the Elderly

Description: Raynaud’s phenomenon affects up to 5% of the general population, causing episodic vasospastic attacks that lead to painful, cold, and discolored fingers. While often occurring as a primary condition, Raynaud’s can also develop secondary to systemic autoimmune diseases such as systemic sclerosis, where attacks tend to be more severe and may progress to digital ulceration. Current treatment options remain limited, with many patients experiencing inadequate symptom control.

Sodium thiosulfate represents a promising therapeutic candidate due to its combined vasodilatory, anti-inflammatory, and anti-oxidative properties. Originally used for cyanide poisoning and calciphylaxis, this drug may offer a novel approach to treating Raynaud’s phenomenon, with the ultimate goal of providing effective chronic therapy for patients with refractory disease.

The STS-001 study is an ongoing proof-of-concept trial at UMCG investigating intravenous sodium thiosulfate administration in Raynaud’s phenomenon. This two-week student project focuses on analyzing available data from the pilot phase, which includes 12 patients with primary Raynaud’s.

The student will examine clinical outcomes from non-invasive vascular laboratory assessments during standardized cooling experiments. Specific analyses include photoplethysmography signal analysis to evaluate digital perfusion dynamics and thermography data to assess temperature recovery patterns following cold provocation. Additionally, the student will analyze hemodynamic parameters obtained from Finapres measurements, providing insight into systemic cardiovascular responses during treatment.

Working alongside the PhD student and vascular lab technicians conducting this study, the student will gain practical experience in clinical research methodology. Beyond data analysis, there will be opportunities to assist with ongoing trial activities, including study visits and patient screening procedures. This project offers valuable hands-on exposure to translational research that may ultimately improve treatment options for patients with Raynaud’s phenomenon.

Experience from student: Statistic training and experience with analysis technical data / signal analysis is helpful.

Patient material handling: Yes, patient will be assisting in clinical study visits.