IRF projects 2020
Are you a young, ambitious, (bio)medical student and would you like to experience doing research in the University Medical Center Groningen? The ISCOMS Research Fellowships (IRF) give students who present their research at ISCOMS the opportunity to experience doing research in the Netherlands and more specifically in the UMCG.
Various Research Institutes of the UMCG are interested in welcoming young and talented foreign (bio)medical students into their institutes and giving them the opportunity to experience what doing research in the UMCG is like. As a student you will get the chance to perform research at a leading institute, meet top-researchers, and learn more about the possibilities of doing a PhD-programme in the Netherlands. The IRF are available for presenting participants of the congress only.
When your abstract is chosen to be presented at our congress, you will receive information about the IRF application. It is important to know that we only have a limited amount of thirty places for students to participate in these projects. Therefore, we have a special application procedure for the IRF-projects.
Besides a lot of (bio)medical projects, there are also a few Research Fellowships that focus more on the technical view of biomedical sciences. Students who study applied physics, biomedical engineering, chemistry or such, will also be able to apply for these very interesting Research Fellowships.
The fellowships take place directly after the congress, from the 8th of June until the 19th of June 2020. This makes it convenient for students to participate in the IRF. Besides this, no additional costs are charged. Accommodation and pocket money will be provided for the duration of the project free of charge.
The IRF are a challenging two week programme in which students are expected to actively participate in research at one of the UMCG Research Institutes and gather a great deal of knowledge related to the topic of research. As a student you get the chance to perform research at a leading institute, meet top-researchers and – more importantly – learn about the possibilities of doing a PhD-programme in the Netherlands. There are many foreign students who have been able to start a PhD-programme in the UMCG thanks to following a fellowship.
The application deadline for the IRF of ISCOMS 2020 is the 4th of April 2020!
Project A: Chromosomal instability in cancer and ageing
Supervisor: Floris Foijer MD PhD
Department: European Research Institute for the Biology of Ageing (ERIBA), UMCG
In each cell division, our complete genome is replicated and segregated equally over the two emerging daughter cells. Cancer cells have an intrinsic tendency to missegregate chromosomes occasionally, a process known as chromosomal instability or CIN. CIN results in cells with an abnormal chromosomal content, a state defined as aneuploid. Indeed, more than two out of three cancers are aneuploid, suggesting that CIN somehow contributes to the transition of normal cells into cancer cells.
Paradoxically, CIN and the resulting aneuploidy pose a growth disadvantage to non-cancer cells, suggesting that cancer cells have found ways to cope with the detrimental consequences of aneuploidy. In our lab, we try to map and understand how aneuploid cells transform into aneuploid cancer cells. We developed state of the art mouse models, in which we can provoke CIN in tissues of choice at time points of choice. Using these models, we have shown that whereas CIN is indeed detrimental for some stem cells, it is remarkably well tolerated by epidermal cells, although aneuploid mouse epidermis appears prematurely aged (Foijer et al, PNAS 2013). Furthermore, we found that CIN alone is not sufficient for cancer, but that predisposing mutations (such as p53 inactivation) are required for aneuploidy to contribute to malignancy (Foijer et al, PNAS 2014; Foijer et al, eLife 2017). The main aim of the lab is to develop new intervention strategies that can selectively kill aneuploid cells. For this, we need to better understand the biology of aneuploid cells and which (epi)genetic alterations are required to transform aneuploid cells into their malignant counterpart.
In this IRF project, you will be introduced into the exciting field of chromosome biology. This includes time-lapse microscopy, cytogenetics, mouse models, pre-clinical intervention, and state of the art technology such as single-cell sequencing (see Bakker et al, Genome Biology 2016) and RNA sequencing. While two weeks will not be sufficient to finish a full project, your IRF stay will reveal how we try to fulfil our mission to identify aneuploidy-killing compounds and we will involve you the experiments that are ongoing at that moment in time. More importantly, you will also learn whether the field of chromosomal instability is a field for you to pursue in your future research avenues. Looking forward to seeing you in June!
Project B: Dietary molecules and immunity in consumers
Supervisor: prof. Paul de Vos PhD
Department: Pathology and Medical Biology
During recent years a disbalance in microbiota communities in the intestine, has been implicated in a large number of Western diseases, such as inflammatory bowel disease, metabolic syndrome, and even autoimmune diseases such as T1D. This growing list of Western diseases correlates with the lowering of dietary fibres in Western diets in comparison to more traditional diets. Dietary fibres and its fermentation products are an important energy source for gut microbiota-generated short-chain fatty acids (SCFAs) that impact inflammation through a variety of mechanisms in mouse models. Also, some dietary fibres and or its degradation products induce specific regulatory responses in T-cells, bind to Toll-like receptors (TLRs) and some stimulate Th1/17-cell responses supporting the host responsive against pathogens. SCFAs are just an example. Other fermentation products such as ligands of aryl hydrocarbon receptors (AHR) or polyamides produced by microbiota probably also influence barrier function, immunity, and endocrine functions. In our research, we identify and study different types of dietary molecules that might impact health. The main focus of the IRF will be on oligosaccharides and dietary fibres and its impact on intestinal immune barrier function.
Project C: Gene regulation in ageing and age-related diseases
Supervisor: Prof. Cornelis F. Calkhoven PhD
Department: European Research Institute for the Biology of Ageing (ERIBA), UMCG
Ageing, metabolic disorders, and cancer share common biological mechanisms. Cellular factors that are involved in sensing nutrient (food) and energy availability are decisively involved in ageing and lifespan determination, as well as in the development of age-related diseases like cancer or metabolic diseases. The primary research focus of the Calkhoven lab is determining how metabolic and other growth signals control the expression of specific sets of genes that can alter the organism’s normal function or contribute to disease.
Currently, the Calkhoven lab studies a specific pathway (mTORC1-pathway) that senses if enough nutrients and energy are available to regulate cell growth through the control of protein synthesis and/or other metabolic processes. The Calkhoven lab is particularly interested in the function of mRNA control elements, protein factors and microRNAs that are involved in mTORC1-controlled processes. Using mouse models, they examine the function of these elements, and other factors, on organismal health and life span determination. In addition, they study the modification of gene regulatory proteins by cellular metabolites and how this regulates cell function under different nutritional conditions. With the aim of ‘translating’ the fundamental research into clinical-pharmacological applications, the lab is also involved in developing reporter systems for potential compound screening strategies.
Project D: Hematopoietic stem cell ageing
Supervisor: Prof. Gerald de Haan PhD
Department: European Research Institute for the Biology of Ageing (ERIBA), UMCG
Project Introduction: The group is interested in a unique genetic and epigenetic programme that distinguishes stem cells from non-stem cells. The research group of Prof. de Haan uses state-of-the-art genomic tools to search for common molecular events in stem cells at distinct phases in hematopoietic development and ageing. The team studies how stem cells can be transplanted, and which mechanisms ensure their proper homing and subsequent engraftment to the bone marrow after transplantation. Stem cells are defined by their ability to self-renew and their ability to differentiate into all lineages within a tissue. The group is addressing how stem cell self-renewal alters with age, and how enhanced stem cell renewal can be exploited in stem cell expansion protocols in vivo and in vitro.
Please check our website for more information: (http://eriba.umcg.nl/groups/ageing-biology-and-stem-cells/)
Project E: Nephrology
Supervisor: Prof. M.H. de Borst MD PhD and J. van den Born PhD
Department: Internal Medicine, Nephrology
In the Nephrology Dept. various projects are running using diverse methodologies (see 1-6). 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 in the specific topic.
- 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 tubular cells.
- Our centre 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 the COMBAT consortium, we focus on the role of the complement system in acute graft failure and chronic transplant dysfunction.
- 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.
- 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 excessive caloric intake leading to obesity and diabetes, excessive 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.
- Various animal (rat) models of proteinuria and progressive renal disease are being studied, in order to unravel the mechanisms of renal damage and to optimize antiproteinuric and renoprotective treatments. Focus points are the RAAS – Vitamin D – FGF23 axis; progression of structural tubulo-interstitial changes; and the interplay of proteinuria and dyslipidaemia.
- Innate immunity and the kidney. Within this research line, we try to unravel the role of the innate immune system (complement system, leukocytes, chemokines) in chronic renal damage in proteinuric and transplanted kidneys. By the intervention of novel heparin(oid) related drugs, we aim to reduce the contribution of inflammation in chronic renal tissue remodelling. Research is largely done in vitro and in experimental models of renal disease.
Project F: Functional genetics to understand complex diseases
Supervisor: prof. Sebo Withoff, PhD
Project Introduction: The Immunogenetics group of the Department of Genetics within the UMCG investigates the role of genetic variation in the aetiology of autoimmune diseases (e.g. coeliac disease, inflammatory bowel disease and multiple sclerosis) and the role of the gut microbiome in health and disease.
The data used for these studies are mostly generated by next generation sequencing. The generation of the data and the analyses requires a broad range of scientific expertise. In this group, a dynamic and highly interactive environment is created in which bioinformaticians, geneticists, statisticians, molecular biologists, stem cell biologists and immunologists work together closely.
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), (d) the enrichment of ‘lymphocyte-specific’ long intergenic non-coding RNAs (lincRNAs) in celiac disease associated loci, and 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 (with currently a strong interest in iPS-derived organ-on-chip technology) and on determining how host genetics affects microbiome composition.
Depending on the background and interests of the student, we will design a working plan for the two-week internship.
Project G: Nanoscale MRI for investigating links between free radical load and infertility
Supervisor: Prof. Romana Schirhagl & Ass. Prof. Aldona Mzyk
Department: Biomedical Engineering
Diamond magnetometry is a new technique which allows nanoscale MRI. It makes use of a defect in diamond which changes its optical properties based on its magnetic surrounding. Since optical signals can be read more sensitively, this method currently holds the sensitivity record for MRI measurements. While the technique is already established in physics, our team is the first to apply this technique in cells. The aim of the project is to use this technique to identify links between infertility and free radical generation. To this end, we are investigating bovine sperm under different stress conditions.
Project H: Locomotor-Respiratory coupling effects on age and on the metabolic cost of walking
Supervisor: Dr. Claudine Lamoth (PhD) & Iris Hagoort (PhD student)
Department: Human Movement Sciences
Human walking is a dynamically stable, highly flexible and adaptive activity that is continuously altered to behavioural goals and prevailing circumstances. To date, it is well recognized that flexibility and adaptability of walking resides in the fact that human motor behaviour is intrinsically variable, and that in-depth analysis of this variability might provide insight into underlying control structures. Changes in walking patterns are also the result of the interaction between different physiological subsystems such as the locomotor, and respiratory systems. Locomotor respiratory coupling (LRC) patterns in humans have been assessed based on the interaction between physiological and motor subsystems; these interactions have implications for movement economy. LRC refers to phase locking of walking and breathing patterns, so that the same number of steps occur during each breath. Depending on for instance the speed of locomotion, people frequently use LRC ratios of 2:1, 2.5:1, 3:1, or 4:1 and sometimes lack coupling implying that breathing and stepping frequencies are independent. With advancing age, changes occur in neuromuscular and respiratory function.
The overall goal of the project is to better understand the flexibility and adaptability of gait patterns and the effect of ageing on this gait adaptability and get insight into possible underlying mechanisms in terms of locomotor-respiratory coupling and movement economy.
Healthy young and healthy older adults will participate in the study and will walk at different conditions. Before the walking conditions, participants are asked to fill in questionnaires, about physical activity, sleep, medication and cognition. In addition, some basic tests quantifying grip strength, dynamic balance, gait capacity will be applied.
You will assist in the data collection, and depending on your specific interest work on a part of the data analysis.
Requirements: Knowledge about how to use Matlab and/or Python codes and scripts and preferable Rstudio and basic statistical knowledge.
Project I: Normothermic machine perfusion of Kidneys
Supervisor: Prof. Henri Leuvenink, PhD & Cyril Moers, MD PhD
Organ transplantation is a life-saving therapy for patients suffering from end-stage organ failure. Due to the growing success of transplantation more patients are on the waiting list and more donors are needed. This leads to an increasing percentage of organs of poor quality.
In the Surgery Research Lab researchers are trying to find new therapies to reduce or repair the injury by using machine perfusion techniques.
The IRF student will be involved in a project in which protective treatments during perfusion will be administered to ex vivo perfused porcine kidneys. The IRF student will work together with a PhD student and will get full insight into the principles of machine perfusion.
A laboratory introductory course will be part of the research stay. Depending on the progress and experience of the student a sub-project will be designed.
It is mandatory for the IRF student to follow the Summer School Transplantation which will take place in the first days of the IRF period. For more information about the Summer School Transplantation you can click on the link below:
Project J: Accelerated vascular ageing in Chronic Kidney Disease (CKD)
Supervisor: Lian Feenstra, MSc & Prof. Jan-Luuk Hillebrands, PhD
Department: Pathology & Medical Biology – Division of Pathology
Project Introduction: Cardiovascular mortality is a major complication in patients suffering from Chronic Kidney Disease (CKD). As a consequence of impaired renal function, CKD patients have multiple cardiovascular risk factors like hypertension, proteinuria and altered electrolyte balances (e.g. hyperphosphatemia and hypercalcemia). An important hallmark of cardiovascular disease in CKD is vascular calcification, in which smooth muscle cells change their phenotype and start to calcify. Recently, plasma-derived secondary calcium-protein particles (CPPs) were proposed to play a role in the vascular calcification process in CKD. CPPs are crystalline nano-aggregates consisting of calcium, phosphate and certain proteins. Although formation of CPPs in CKD is enhanced, the mechanism by which they may enhance vascular calcification is still largely elusive.
At the Department of Pathology & Medical Biology we are currently investigating the potential mechanism(s) of CPP-induced vascular calcification with a specific focus on CPP-induced vascular ageing and crosstalk between the endothelium and smooth muscle cells. The IRF candidate will participate in this project. First, the student will be introduced in the field of vascular biology and renal disease. Next, under the supervision of a PhD-student the IRF candidate will participate in lab experiments using various techniques, including cell culture, (immuno)histochemical staining on cells and (human) vascular tissue, and gene expression analysis (PCR). The exact experimental setup will be determined during the project with input from the IRF candidate.
Project K: The pathobiology of lymphoma
Supervisor: Lydia Visser, PhD
Department: Pathology and Medical Biology
We will look at different aspects of lymphoma research by looking at the expression of proteins, drug sensitivity, combination therapy or effect on the micro-environment. We can use techniques as immunohistochemistry, cell culture, flow cytometry, western blot, ELISA and metabolic assays.
Project L: Physiological adaptation of the heart in response to exercise
Supervisor: Daan Westenbrink, MD PhD & Kirsten T. Nijholt, BSc, MD/PhD Candidate
Heart failure (HF) is a worldwide disease affecting many patients by leading to frequent hospitalizations, high mortality rates and by limiting quality of life. Unfortunately, effective therapies directed at the underlying pathophysiology of HF are still lacking. The heart undergoes two types of remodelling to maintain cardiac function when exposed to stress. Increasing our understanding of pathological and physiological growth may enable to lead to the development of novel therapeutic targets focused at the cause of HF rather than the consequences. Our project focuses on a potential target that is involved in the physiological, healthy growth of the heart in response to exercise.
A Kinase Interacting Protein 1 (AKIP1) has been discovered as a pro-hypertrophic gene. Our department has shown that AKIP1 does not influence the adaptation of the heart to pathological stress, such as a myocardial infarction. In vitro experiments of cultured cardiomyocytes have shown that AKIP1 stimulates a physiological type of growth by activation of a specific signalling pathway. In vivo we have observed that AKIP1 is indeed a regulator of physiological hypertrophy in response to exercise. However, how AKIP1 regulates this physiological, healthy growth is still unknown. Preliminary results suggest that an increase in mitochondrial content may contribute to the beneficial growth effects. Therefore, we aim to further unravel the underlying mechanism by which AKIP1 modulates physiological hypertrophy.
In this project, a mouse model with cardiomyocyte-specific overexpression of AKIP1 will be subjected to a model of voluntary wheel running. Measuring exercise parameters and cardiac function, where after heart tissue will be analysed for histology and biochemistry. These analyses are mainly performed using techniques such as microscopy, polymerase chain reaction and Western blot. As a student, you will be able to become acquainted with the described exercise model and to contribute to the analysis of cardiac tissue.
Project M: Detection of neonatal jaundice
Supervisor: Christian Hulzebos MD PhD
Timely detection of jaundice is essential, because severe hyperbilirubinemia may cause brain damage when left untreated. Detection on jaundice relies mainly on visual inspection, whereas transcutaneous bilirubin (TcB) measurements seem more adequate. There are a few transcutaneous bilirubinometers on the market now, but data on comparison of TcB measurements between these instruments are scarce. Research questions: 1. How is screening of jaundice done in the local or national setting of the student? It would be very informative if the students could analyse their own data. 2. To compare TcB data of two bilirubinometers (data analysis) with results of total serum bilirubin.
Project N: Cigarette smoke and loss of E-cadherin as factors contributing to accelerated lung ageing in COPD.
Supervisor: Prof. Irene Heijink PhD, Corry-Anke Brandsma PhD and Kingsley Okechukwu Nwozor, MSc (PhD Candidate)
Department: Pathology and Medical Biology
Chronic obstructive pulmonary disease (COPD) is a chronic, life-threatening lung disease with increasing morbidity and mortality, especially in the elderly. With the ageing of the population, the high social and economic burden associated with COPD is expected to increase further. Currently, COPD is the third leading cause of death worldwide. The main risk factor for COPD is the inhalation of noxious gases, including cigarette smoke, job-related exposures and air pollution. COPD is characterized by an abnormal inflammatory process within the lungs in response to smoking, leading to lung tissue damage which drives remodelling, including small airway disease and emphysematous lung tissue destruction.
Background: Previous research of our group has established that cigarette smoke negatively affects the airway epithelial barrier function, thereby making both the epithelium and the mesenchyme more vulnerable to environmental insults. It has also been demonstrated that there is a significant decrease in the expression of genes responsible for tight and apical junction assembly (for example, CDH1 gene which encodes E-cadherin), in the airway epithelium with ageing, as well as in COPD patients, when compared to controls.
Aim: To investigate if the loss of E-cadherin and the resultant loss of barrier function lead to increased cellular senescence.
Approach: Human bronchial epithelial cell line (16HBE cell line), which is widely used to model barrier function of the airway epithelium, will be treated with cigarette smoke extract (CSE), and barrier function will be assessed using the Electric Cell-substrate Impedance Sensing (ECIS) system. Total RNA will also be isolated, cDNA synthesized and E-cadherin gene expression measured using the RT-qPCR technique. Furthermore, the CRISPR/Cas E-cadherin knockdown 16HBE cell line will be cultured, followed by RNA isolation and quantifying the p16 and p21 genes (which serve as senescence markers), using the RT-qPCR technique.
Project O: Endoplasmatic reticulum stress as driver of remodelling of lung extracellular matrix in healthy lung ageing
Supervisor: Prof. Janette Burgess, PhD & Maunick Lefin Koloko Ngassie, MSc
Department: Cell Biology
Project Introduction: The principal role of the lung is to provide oxygen from the inhaled air to the bloodstream and to exhale carbon dioxide. Worldwide increasingly ageing populations are becoming a major concern for healthcare systems, particularly impacted by the increased prevalence of lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis in the elderly. Connective tissue of the lung is largely constituted by extracellular matrix (ECM) molecules that play an important role in maintaining the structure and functionality of the lung. Ageing-associated changes in ECM contribute to changes in the structure of the lung tissues. Ageing also affects different cellular processes including endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR).
The endoplasmatic reticulum (ER) is an essential organelle where secreted and transmembrane proteins are synthesized and folded. With increasing age, protein folding capacity diminishes due to progressive failure of chaperoning systems, leading to an increased ER stress. Ageing-associated changes in ERS and UPR might promote cellular senescence, add a brief description of what this means. Senescent cells develop a senescence-associated secretory profile characterized by expression and secretion of inflammatory cytokines and growth factors. Thus, mesenchymal lung cells can develop enhanced proliferation and drive fibrosis via paracrine/autocrine effects and synergize ER Stress, UPR and ECM changes in a feed-forward way to promote remodelling. Therefore, there is a considerable interest in investigating the possible link between age-associated changes in ERS/UPR and ECM remodelling in the lung.
This project aims to understand how ageing alters mesenchymal cell responses to ERS and the impact on senescence and subsequent changes in the ECM microenvironment in the lungs.
During your stay in our research facility, you will have the opportunity to have an overview in experimental pulmonology and Inflammation research and experience the collaboration between basic biomedical research and clinical science. We look forward in seeing you in June.
Project P: Composition and structure of portal vein thrombi
Supervisor: E.G. Driever, MSc & Prof. J.A. Lisman, PhD
Our group focuses on haemostatic abnormalities in patients with liver diseases. A common complication in patients with chronic liver disease is portal vein thrombosis (PVT); a complete or partial blockage of the portal vein or its intrahepatic branches. Risk factors for the development of PVT remain under investigation, and there is no consensus on treatment and prevention of the condition. Although PVT is treated similar to the treatment of deep venous thrombosis, and thereby it is assumed that portal vein thrombi resemble deep venous thrombi, the composition of portal vein thrombi has never been studied in detail. In this project, you will use immunohistochemical techniques to study the structure and composition of portal vein thrombi.
Project Q: Generation Y at work: who succeeds? A life-course perspective on mental health and work from childhood to young adulthood
Supervisor: Prof. dr. Ute Bültmann, PhD; Dr. Iris Arends, PhD and/or Dr. Karin Veldman, PhD
Department: Health Sciences
Project Introduction: A considerable number of adolescents (i.e. 10 to 25%) has to deal with the burden of mental health problems, and these problems often track into adulthood. Mental health problems comprise various emotional and behavioural problems (e.g., depressive symptoms, anxiety, aggressive and delinquent behaviour). Adolescents’ mental health problems can have long-lasting negative consequences, as they may have a negative effect on the transition from school to work. Adolescents suffering from mental health problems are at risk of dropping out of high school, and when entering adulthood, to be unemployed and earning lower wages.
Finishing a study and finding a job are major milestones in young adulthood. Especially today, where starters at the labour market and young working adults have to earn a living in a new world of work (e.g. more temporary work, multiple jobs) with transformed labour markets (e.g. more self-employment and a 24/7 work cycle in a global economy). The school-to-work transition into a new world of work evidently challenges mental health. Therefore, the aim of the NWO Vici-project ‘Today’s youth is tomorrow’s workforce: generation Y at work’ is to examine the complex relationship between mental health and work from childhood to young adulthood, using a life course perspective.
Unique data of the TRAILS study (TRacking Adolescents’ Individuals Lives Survey) with 18 years of follow-up will be used to answer relevant research questions. TRAILS is a Dutch prospective cohort study, and follows 2300 children from the age of 10/11 years into young adulthood, currently 27/28 years. An overview of available data of the TRAILS study can be found at the website (www.trails.nl). The specific research question for the IRF students will be determined – in consultation with the students – at the start of the IRF project.
Project T: Personalized medicine in pharmacological lung cancer treatment
Supervisor: Job FM van Boven PharmD, PhD
Department: Clinical Pharmacy & Pharmacology
Project Introduction: The department of Clinical Pharmacy & Pharmacology of the University Medical Centre Groningen (UMCG) performs preclinical, translational and clinical research. Our research focusses on personalized medicine and targeted pharmacological therapy, mostly applied to oncology.
Topics within personalised medicine focus on optimisation of pharmacotherapy (individual response variability, therapeutic drug monitoring, pharmacogenetics, biomarkers, molecular imaging), conducting large clinical trials with investigational medicinal products, drug utilisation research (real-world outcomes such as medication adherence, safety and cost-effectiveness) and development and regulatory assessment of new drugs and dosage forms.
We offer a 2-week IRF project that will focus on drug-related issues in patients with lung cancer. Are lung cancer drugs’ clinical trial effects equally effective in the real-world? Do the current lung cancer drug trials reflect real-world patients’ characteristics? What is needed for personalized medicine in lung cancer treatment? What can we do to optimize adherence to treatment? To assess these issues, you can learn about novel drug monitoring tools using nuclear imaging, pharmacogenetics, dried blood spots, eHealth and hair analysis and work with our experienced multidisciplinary team of physicians, pharmacists and clinical researchers.
For questions regarding this project, please contact: dr. J.F.M. van Boven, assistant professor of Drug Utilization Research (firstname.lastname@example.org)
Project U: Surgery related muscle loss (SRML); is there a difference in SRML between liver resection and local ablation for colorectal liver metastasis (CRLM)?
Supervisor: Prof. J.M. Klaase, MD PhD
Department: Hepatobiliary & Pancreatic Surgery
Surgery related muscle loss can lead to impaired quality of life and fatigue on the mid to longterm.
Preliminary results from our prospective ‘muscle power study’ show in 58% of patients a remarkable SRML loss of >10% after major abdominal surgery (measured with handheld ultrasound) and in 82% of patients a loss of muscle strength of >20%. After liver resection for CRLM, we found SRML in more than half of our patients (measured with total psoas area on the abdominal CT scan at the level of L3). Factors associated with SRLM were diabetes, COPD and low preoperative muscle mass. The hypothesis is that SRML is less pronounced after ablative procedures, which could be an extra argument for this percutaneous procedure. During the four weeks research period we will assess SRML making use of CT-scans in a cohort of patients that underwent percutaneous radiofrequency ablation (RFA) or Microwave ablation (MWA) for CRLM. We will look for factors associated with SRML after RFA/MWA.
Project V: LifelinesNEXT - Introduction to scientific challenges in broad phenotyped cohorts
Supervisor: Prof. Sicco Scherjon MD PhD
Project Introduction: LifelinesNEXT is a prospective birth cohort of mothers, fathers and babies, which includes extensive sample collection starting at 12 weeks of gestational age until at least the age of one year. A variety of biomaterials is collected including blood, stool and breastmilk at multiple time points. Data on environmental, social and medical factors are collected via questionnaires at 14 time points. LifelinesNEXT offers an opportunity to relate integrated information on microbiome, metabolism, immunology, genetics, epigenetics and environmental influences. The LifelinesNEXT cohort will consist of ~1500 pregnant mothers, their new-borns and partners. In this project, we will introduce the student to the many scientific opportunities that occur in a broad phenotyped cohort and LifelinesNEXT in particular.
During the 2 weeks project students will get acquainted with the ongoing process of including pregnant women to the study, the extensive data collection on mother and child, and the preparation of biosamples and the first data analysis.
The course will cover three aspects of research in birth cohorts:
- Bio sample collection
Students will accompany a research nurse during their home visits to participants. Participating in the elaborate research project LifelinesNEXT requires a lot of effort from the participants. Therefore, LifelinesNEXT gives ample attention to the warm contact with participants and visits them at least 4 times.
- Lab introduction
All kinds of biomaterials collected in LifelinesNEXT (breastmilk, blood and stool) are processed and prepared for genotyping at the laboratories of the Genetics department UMCG. By participating in this process, students will be introduced in the fascinating world of genetics.
- Data analysis
The first data from questionnaires became available recently. Our students will perform data analysis to give insight in the inclusion process and provide a first characterisation of LIFELINESNEXT participants. The students will prepare a report on several topics, e.g. food intake of included newborns and characteristics of exclusively breastfed babies.
Project X: Cardiovascular disease in lung cancer screening with computed tomography
Supervisor: prof. G.H. de Bock PhD & M. Vonder, PhD
Project Introduction: Currently lung cancer screening with computed tomography is implemented worldwide. Besides screening the chest for lung nodules, this also offers the unique opportunity to screen the coronary arteries of the heart for calcifications. We know from several large studies that the number of coronary calcifications is a very good predictor of cardiovascular disease in the near future. We are currently working on a big multi-centre trial in the Netherlands and China to evaluate lung cancer, COPD and cardiovascular disease in different populations. The current clinical project focusses on quantifying coronary calcifications on chest CT and the reaction of this imaging biomarker with traditional risk factors.