ISCOMS 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: Jaap van den Born MD PhD, prof. Stefan P. Berger MD PhD

Field of research: Nephrology 

Description: In Nephrology Dept. various projects are running using diverse methodologies. You are invited to express your interest in one of the following fields: clinical, epidemiological, human or animal in vivo or in vitro experimental research. Please indicate which sub-project interests you the most and provide motivation for your choice.

1. Proteinuria-induced complement activation

Patients with renal disease and progressive renal function loss, are being studied with respect to the mechanisms via which the urinary protein leakage results in renal function loss. We aim to modulate proteinuria-driven complement activation on endothelial and tubular cells.

2. Transplant outcomes and risk factors

Our center also 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. Within this cohort we try to entangle which factors associate/contribute to transplant loss and mortality.

3. Renal risk factors

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. Lifestyle and the kidney

Many lifestyle factors are involved in the risk of long term renal function loss. These include smoking as well as nutritional habits, such as excess caloric intake leading to obesity and diabetes, excess sodium intake and sedentary lifestyle. The mechanisms of renal damage induced by these lifestyle factors are being studied in patients as well as experimental animals, and the effect of lifestyle intervention measures on the course of renal disease is being studied. Nutritional monitoring is part of this project.

5. Endothelium and renal disease

Endothelial dysfunction highly contributes to progression of renal and cardiovascular diseases. We are interested in the effects of uremic 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 renal patients.

6. Immunity and the kidney.

Within this research line we try to unravel the role of the immune system (complement system, leukocytes, endothelial cells) in chronic renal damage in proteinuric and transplanted kidneys. B-cell, endothelial and complement profiling will be associated with clinical outcome parameters.

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

Supervisor: Alexandra Androni, PhD-student

Field of research: Medical education

Description: This project allows you to validate a student engagement observation instrument by assessing its validity and inter-rater reliability. You will work with previously collected data, where researchers used an observation tool to score student engagement behaviour. Since this is a non-clinical project, you will focus on educational theories, literature on educational models, and instruments used to measure student engagement in higher education.

You will start by exploring medical education literature before discussing the observation instrument used during data collection. Afterwards, you will analyse the data and propose a method to validate sub-categories of the instrument. The validation strategies you might work on include content-related, construct-related, or criterion-related validation.

Your research question will be adapted based on your interests and competences, but will always relate to validating the student engagement observation instrument. Ideally, you should have a basic understanding of statistics (SPSS, STATA, etc.) and some experience with quantitative research.

Through this project, you will gain experience working in an interdisciplinary team of medical education researchers, learn about the process of applying to and attending medical school at the University of Groningen, and develop your skills in combining qualitative and quantitative research methods!

Experience from student: Looking for a student with interest in basic statistical knowledge and quantitative research.

Supervisor: Prof. Adriaan Voors, MD PhD

Field of research: Cardiology

Description: Atrioventricular node congestion is considered as the main driver of worsening of heart failure and a poor diuretic response is associated with worse clinical outcomes in patients who are hospitalized for acute heart failure. Several studies have identified clinical predictors of a poor diuretic response. However, the underlying mechanisms for a poor diuretic response leading to residual congestion are not completely understood. We therefore propose to use a plasma proteomic approach to study pathophysiological pathways related to a poor diuretic response, potentially providing novel molecular targets for therapy.  From a cohort of 1020 patients who are hospitalized for acute heart failure, LC-MS proteomics has been performed and includes >1000 unique proteins. You will perform a differential expression analysis to identify proteins that are up- or downregulated in patients with residual congestion. Using AI techniques, these protein profiles will be translated into pathways. You will interpret these pathways to identify potential future targets for novel therapies to improve congestion in patients with heart failure.

Experience from student: Looking for a student who is proficient in working with R Studio.

Supervisor: Kelly Cremer, PhD candidate, Professor J.P.P.M. de Vries, MD, PhD, B. Saleem MD PhD

Field of research: Infectious diseases

Description: You will work with one of our PhD students on the project titled: ‘Antibiotic suppression therapy in patients with a vascular graft or endograft infection’. Vascular graft or endograft infection is a rare condition with high morbidity and mortality rates. The gold standard treatment is surgery, which involves explanting the infected graft, performing a new reconstruction and treating it with antibiotics. However, this procedure is not suitable for all patients due to comorbidities. As an alternative, livelong antibiotic suppression therapy is often considered. While this approach is viewed as inferior, it may be the only viable option for some patients, despite the potential side effects associated with prolonged antibiotic use. You will contribute to a portion of the statistical analysis under the guidance of the PhD student. Additionally, you will write part of the introduction for the article, based on a thorough research of existing literature.

Experience from student: Looking for a student with interest in basic statistical knowledge and quantitative research.

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. Cor Calkhoven MD PhD, PhD-student Clément Karch

Field of research: ERIBA, Ageing biology

Description: Breast cancer is one of the most prevalent cancers worldwide. Breast cancer can be classified into different subtypes requiring different treatment, and despite the existence of treatments for most types of breast cancers, prognosis for metastatic breast cancer is still poor. To develop more specific and effective treatment it is crucial to understand the underlying cellular and molecular mechanisms that specify a certain breast cancer subtype.

The transcription factor C/EBPβ-LIP is specifically overexpressed in triple-negative breast cancer and was shown to be involved in cell migration, cancer metabolism and possibly immune evasion. You will work on aspects of oncogenic functions of C/EBPβ-LIP. The project will likely involve cell culture, transfection, and immunoblotting techniques as well as assays for cancer cell proliferation and survival.

Experience from student: Looking for a student with laboratory experience in molecular biology.

Supervisor: Dr. Priya Vart

Field of research: Urology and Nephrology

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 aims 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 data analysis with any statistical software, preferably SPSS, Stata or R.

Supervisor: Prof. dr. Daan Westenbrink

Field of research: Cardiology

Description: Novel organ preservation strategies including oxygenated hypothermic machine perfusion (HOPE) are shown to successfully preserve donor hearts, and to even extend preservation time in donation after brain death hearts. However, up to date, no serial report is available on prolonged HOPE of donation after circulatory death (DCD) hearts. In this study, we aim to evaluate whether DCD hearts can be successfully preserved using HOPE for a prolonged period of time.

This study is implemented in the existing infrastructure of organ donation in the Netherlands. DCD donor hearts declined for clinical transplantation are included in the study. Hearts are preserved for either 4 or 8 hours using HOPE. After preservation, hearts are evaluated during normothermic machine preservation (2 hours) using pressure-volume loop analyses. In addition, perfusate samples and left ventricular biopsies are taken during both HOPE and NMP.

During this project, you will perform immunofluorescent staining and evaluate the stained biopsies from the donor heart. If a donor heart perfusion is performed during the research fellowship, you have the opportunity to observe the experiment.  

Experience from student: Looking for a student with laboratory experience with histological staining.

Supervisor: Prof. dr. Ilya Nolte Phd, PhD student, Prof. Peter van der Most

Field of research: Genetic Epidemiology & Bioinformatics

Description: Over 850 million individuals world-wide are affected by Chronic kidney failure. It is most commonly diagnosed using the biomarker “serum creatinine”, which is used to calculate the estimated glomerular filtration rate (abbreviated as eGFRcrea). However, this eGFRcrea is only an estimate, and creatinine levels are affected by muscle mass as well as kidney function.

An alternative measure for kidney function is therefore desirable. As it happens, urinary creatinine (when collected over a full 24 hours) is considered a reliable measure of muscle mass. We could potentially make a better estimate of kidney function by including both serum and urinary creatinine into a single measure: the creatinine clearance (CC).

The aim of this project is to identify genes affecting CC. Over the past year, we have conducted a genome-wide association study (GWAS) over the Lifelines population cohort. Here, we identified several genetic loci affecting CC in our population. The next step is to validate these loci; to describe them and place them into the context of creatinine metabolism & function. We will therefore investigate:

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

–      Which genes are located within these loci;

–      What their functions are;

–      To which pathways they belong;

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

The ultimate goal is to provide a list of genes that should be prioritized for follow-up analyses in the lab, and whether CC is a valid (or superior) alternative for eGFRcrea.

Experience from student: Looking for a student with experience with the statistical software R, as this project will be fully computer based.

Supervisor: Prof. Romana Schirhagl, PhD

Field of research: Biophysics

Description: Free radicals are transient, reactive molecules generated during normal cell metabolism, serving as key indicators of cellular stress. Hence, these reactive oxygen species (ROS) play an important role in various disease models. However, their fleeting nature complicates their detection. To tackle this, fluorescent Nanodiamonds (FNDs) with NV centers enable nanoscale detection of free radicals in living cells. T1-relaxometry, a specialized diamond magnetometer technique can be employed to quantify radical species inside live cells in real time.

Experience from student: Looking for a student with biology laboratory experience and microscopy experience.

Supervisor: Maria Eduarda da Silva, PhD Candidate, Professor Dineke Verbeek PhD, Prof. Marco Carvalho Filho, PHD

Field of research: Physician-scientist professional identity formation

Description: In the ever-evolving landscape of medicine and research, physician-scientists bridge the gap between clinical care and scientific innovation. While their role is indispensable, recruiting, training, and retaining physician-scientists remains a global challenge, with a notable decline in research interest among physicians.

This project explores the professional identity formation (PIF) of physician-scientists, focusing on how they navigate and integrate their dual identities as clinicians and researchers. Using a mixed-methods approach, we aim to uncover the motivations, challenges, and experiences of medical students pursuing this demanding path. The insights gained will inform strategies to refine educational programs and support the next generation of physician-scientists.

Experience from student: Looking for a student with a background in qualitative research or an interest in medical education.

This project focuses on the development and characterization of a library of nanogels with different sizes and stiffnesses for the identification of optimal properties to overcome the above-mentioned obstacles. Nanogels are soft colloidal particles consisting of a crosslinked polymer network with tuneable properties, high biocompatibility and high loading capacity for hydrophilic drugs, such as DNA, RNA, proteins and peptides. 

Poly(N-isopropylmethacrylamide) (p(NIPMAM)) nanogels are synthesized by precipitation polymerization. Nanogel properties such as size, charge and morphology will be investigated using different techniques, including dynamic light scattering, zeta potential measurement, atomic force microscopy and nanoparticle tracking analysis. Subsequently, the nanogels will be tested for increased blood circulation time, transport across the BBB and penetration into tumour spheroids.

Experience from student: Knowledge of nanotechnology or biology 

Supervisor: Prof. Hélder A. Santos

Field of research: Biomedical technology & immunotherapy

Description: Glioblastoma (GB) is the most aggressive and lethal primary brain tumour in adults, with current treatment options providing limited efficacy (Fyllingen et al., 2021). Surgical resection followed by adjuvant therapy is the standard of care; however, tumour recurrence is common due to the presence of residual cancer cells (Youngblood et al., 2021). This project proposes the development of a novel therapeutic approach utilizing an in-situ injectable and 3D-printable composite loaded with nano/micro polymeric particles (PPs) to deliver a combination of small molecule drugs and antibodies targeting GB cells post-surgery. Additionally, the hydrogel formulation will be loaded into a triblock copolymer matrix to allow its 3D-printability.

This novel medical technology will be formulated using biocompatible materials to ensure sustained release and prolonged retention at the surgical site as 3D-bioprintable scaffolds. PPs will encapsulate small molecule chemotherapeutic agents and monoclonal antibodies specifically designed to target GB cells while sparing healthy brain tissue. The synergistic action of these agents aims to eradicate residual cancer cells, inhibit angiogenesis, and modulate the tumour microenvironment to prevent recurrence.

The 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.

The successful development of this in-situ injectable hydrogel loaded with drug delivery particles has the potential to revolutionize post-surgical treatment strategies for GB patients by providing a targeted and sustained drug delivery platform capable of eradicating residual tumour cells while minimizing systemic toxicity and improving patient outcomes after GB resection.

Experience from student: Looking for a student with a background in chemistry, biomedical engineering, cell biology or pharmacy.

Supervisor:  Prof. Martina Schmidt; cand.PhD, Prof. Ana Manzano Covarrubias

Field of research: Molecular Pharmacology Department, Faculty of Science and Engineering

Description: Influenza A H1N1 and human adenovirus type C (HAdV-C5) are two common viruses that cause respiratory infections and have been linked to exacerbation in COPD and asthma patients. Both viruses are able to infect both the upper and lower respiratory tract and cause significant cell damage and death. Previous research in the group has found ferroptosis-like features caused by the infection of these two viruses. The aim of this project is to further characterize ferroptosis markers and use inhibitors to evaluate their effect in infection. Special focus will be given to mitochondrial structure and function, next to the crosstalk between calcium and cyclic nucleotides. Lipidomics and bioinformatics might be included in part, depending on the stage of the project flow.

Experience from students: Looking for a student with knowledge of basic bioinformatics and experience with lab experiments.

Supervisor: Prof. E.I Metting, PhD

Field of research: Epidemiology

Description: This project investigates differences in the perspectives and needs of COPD patients regarding digital healthcare, based on the mode of questionnaire submission—paper versus online. The data, collected from approximately 200 patients in the Netherlands and Belgium, includes 50% who completed the survey on paper and 50% online. The survey focuses on patients’ digital literacy, willingness to use eHealth, and their expectations about how digital healthcare could help manage their disease.

A key question is whether patients who submit paper-based questionnaires differ in digital skills or specific concerns compared to those who respond online. For example, are paper questionnaire respondents less digitally literate or more apprehensive about using eHealth? The goal is to identify potential differences between these groups to inform targeted strategies for eHealth implementation and adoption.

The student will work with survey data that includes many categorical variables, performing statistical analyses to identify differences between the groups. Findings will help shape more inclusive digital healthcare solutions for patients with COPD.

The outcomes of this project are expected to contribute to improving healthcare accessibility and innovation by addressing the diverse needs of patients with varying levels of digital literacy.

Experience student: Looking for a student with proficiency in statistical analysis, especially with categorical data (e.g., Chi-square tests, logistic regression); Experience with statistical software such as SPSS (preferred) or R (if using R, sufficient expertise is required); Ability to work with survey data and a basic understanding of healthcare and its current challenges, particularly regarding digital health solutions.

Supervisor: Prof. J.K. Kruit, PhD

Field of research: Pediatrics/Obstetric and gynecology

Description: 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 model of GDM. Offspring of GDM mice showed impaired glucose tolerance, indicating disturbances in glucose control. In this project, you will determine whether the development of the endocrine pancreas in the offspring is affected by GDM.

To determine the effect of GDM on endocrine pancreas development, we performed RNA sequencing on islet samples. You will perform an unbiased transcriptome analysis on these samples to determine whether gene transcription is affected by GDM. Changes in gene expression can be verified on histological samples using pancreatic tissue material. For this, you will perform an immunofluorescent or immunohistochemical staining for proteins involved in for example beta-cell proliferation, apoptosis or dedifferentiation.

Experience from student: Looking for a student with lab experience in immunological staining.

Supervisor: Dr. S. Aluwini, Dr. R van der Walle

Field of research: Radiation oncology

Description: After primary treatment of prostate cancer (PCa), more than 20% of patients develop a biochemical recurrence (BCR) mostly due to metastatic disease. The prognosis of metastatic PCa is highly heterogeneous, with the number of metastases and tumor location being important prognostic factors for PCa-specific mortality. PSMA-PET is the current imaging modality of choice for prostate cancer. It gained popularity due to its improved detection accuracy compared to conventional imaging techniques. This improved diagnostic accuracy is crucial for understanding the heterogeneity in prognosis and opens new options for tailored therapeutic approaches. To optimize the potential of these treatment opportunities it is crucial to gain insight into spreading patterns of recurrences. The aim of this project is therefore to analyze recurrence patterns following primary treatment based on PSMA-PET. Prospective data of over 500 patients enrolled in two KWF granted RCT’s (ADOPT and PERYTON) are used for this analysis.

Experience from student: Looking for a student with basic statistical skills and knowledge of radiology.

Supervisor: Ilja M. Nolte, PhD; Senior researcher in the Unit of Genetic Epidemiology and Bioinformatics;

Field of research: Epidemiology

Description: Adolescence is a transformative period of life, marked by significant physical, emotional, and social changes. Early adulthood represents a critical phase of transition from adolescence to adulthood. These transitions can increase vulnerability to mental health problems in young people. Nearly 14% of adolescents aged 10–19 worldwide are affected by mental health conditions, with almost half emerging before 14 years old. In the Netherlands, over half of young adults aged 16 to 25 reported experiencing mental health problems in 2023. Common mental health problems include emotional problems, such as depression and anxiety disorders, as well as behavioral problems like attention deficit hyperactivity disorder (ADHD) and Oppositional Defiant Disorder (ODD).

Mental health problems are influenced by genetic factors. Previous research based on twin and family studies indicates that heritability is 30%-60% for anxiety, 31%-42% for depression, 77%-88% for ADHD, and 50%-65% for aggressive behavior. More recent genome-wide association studies (GWAS) allow to additionally assess genetic risk for mental disorders by generating polygenic scores (PRS), which aggregate the effects of multiple genetic variants. While genetic factors contribute to the risk of mental disorders, environmental factors may also play an important role. Physical activity, as a modifiable lifestyle factor, is recognized as a protective factor for mental health throughout the lifespan. Literature has shown, for instance, that higher physical activity levels are associated with a lower incidence of depression in older adults. Furthermore, more frequent exercise was associated with reduced rule-breaking behaviors in children aged 9-10 years, no association was found with anxiety, depression, ADHD, or aggression, which may suggest that age specific effects play a role.

Although the effects of physical activity and genetic factors on mental health have been established, investigating the interplay between genetic factors and physical activity may be an important next step for a comprehensive understanding of mental health problems. Evidence of interaction between physical activity and genetic risk for anxiety and aggression is limited so far, in particular in adolescents and young adults.

This study therefore aims to investigate how physical activity, polygenic risk, and their interaction are associated with mental health problems in adolescence. The interaction term will be used to test whether the effect of physical activity on mental health problems is different in individuals at high genetic risk versus those that are at low risk, with a particular interest to assess if physical activity has more impact on mental health problems in adolescents at high genetic risk.

Experience from student: Looking for a student with basic lab skills.

Supervisor: Dr. G.A. Holtman, PhD

Field of research: Medicine general and internal

Description:  In children with acute abdominal pain, general practitioners (GPs) often face difficulties in distinguishing acute appendicitis (AA) from common self-limiting conditions. This causes 19% of AA cases not being recognized at first GP consultation. Furthermore, about 70% of referred children with acute abdominal pain will not have AA. This results in a significant burden for patients, family and the healthcare system. The objective is to evaluate the impact of using a diagnostic strategy, consisting of a clinical prediction rule (cPR) including C-reactive point of care testing (CRP-POCT) for AA, among children presenting with acute abdominal pain in primary care, as compared with usual care. This is a cluster randomized controlled trial in primary care with a process evaluation.

Experience from student: Looking for a student with experience with qualitative or quantitative data analysis.

Supervisor: Dr. G.A. Holtman, PhD

Field of research: Medicine general and internal

Description: Currently, there are no guidelines for blood tests in children with persistent fatigue in general practice. In two thirds of these children GPs order several blood tests, but we do not know whether this is cost-effective. It is often assumed that parents demand blood tests. Different expectations among GPs, children and parents lead to frustration, fear and uncertainty. The main aim of this study is to provide insight into the cascade of blood test ordering in children 4 to 18 years presenting with persistent fatigue in general practice. For common and acceptable test strategies (e.g. ‘a limited strategy’) we will evaluate the impact on costs, missed or falsely diagnosed somatic conditions, and quality of life and whether these test strategies have the potential to be cost-effective. In addition, our aim is to evaluate communication and decision making of ordering blood tests in various test strategies.

Experience from student: Looking for a student with experience in quantitative data analysis preferably with R.