About our research group/lab
Our research aims to improve outcomes after organ transplantation by understanding and modifying the biological processes that determine long-term graft function.
We focus on:
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understanding transplant rejection and degenerative processes
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modifying alloimmune responses
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identifying biomarkers for the early detection of rejection
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modulating organ immunity
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stimulating tissue regeneration and repair
Our research focuses primarily on kidney transplantation, while also extending to other transplantable organs. We combine access to clinical samples from transplant recipients with advanced stem cell-derived organoid models to study organ injury, disease and repair.
Research Lines
1. Transplantation Immunology
We work towards the concept of “one kidney for life”, in which a better understanding and targeted modification of the alloimmune response are essential.
Our research includes strategies to modify donor organs and make them less visible to the recipient’s immune system, as well as the development of novel donor-specific therapies to target the alloimmune response.
We also investigate:
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virus-specific immunity in transplant recipients
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the potential role of virus-specific immune responses in transplant rejection
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HLA- and non-HLA-reactive T cells
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mechanisms underlying rejection and fibrosis in kidney transplant recipients
Our studies combine molecular techniques, cell culture and serological analyses.
2. Immune Monitoring
The alloimmune response is a major cause of transplant rejection and can negatively affect long-term graft outcomes. We investigate biomarkers in blood and urine that reflect the alloimmune response and may help predict or detect rejection at an early stage.
A particular focus is on donor-derived cell-free DNA (dd-cfDNA) as a minimally invasive biomarker of graft injury and rejection.
Our research aims to:
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identify biomarkers that predict or detect rejection
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develop combinations of biomarkers for improved diagnostic accuracy
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reduce the need for invasive kidney biopsies
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develop and validate technical approaches for clinical implementation
3. Kidney Organoid Disease Modelling
We use kidney organoids derived from healthy and patient-specific induced pluripotent stem cells (iPSCs) to model kidney disease, injury and repair.
Our models are used to study:
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transplant-induced kidney injury
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genetic kidney diseases, including ADPKD and CAKUT
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drug and compound toxicity
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fibrosis and tissue repair
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interactions between kidney cells and the immune system
We have developed methods to incorporate stem cell-derived immune cells and endothelial cells into kidney organoids. In addition, we have developed multi-organ-on-chip platforms to create more physiologically relevant models of disease and therapeutic intervention.
Our organoid systems provide a range of readouts to monitor cellular toxicity, fibrosis, tissue injury and regeneration, enabling us to investigate mechanisms of disease and identify potential new therapeutic strategies.
Overcoming immunological barriers
The ABO blood group and HLA tissue type can be a formidable barrier to organ transplantation. We work on several strategies to either transiently or permanently remove ABO blood groups to allow transplantation over the ABO blood group barrier without treating the patient. We make use of cell culture systems and kidney organoids, as well as discarded human organs during machine perfusion. Additionally, we work on Chimeric HLA Antibody Receptor (CHAR) T cells as specific HLA-desensitization therapy in order to facilitate transplantation for highly sensitized transplant candidates. We use various methods for genetically redirecting T cells towards alloreactive B cells.
Virus-specific immunity in transplant recipients
Transplant patients have to take lifelong immunosuppressive drugs to prevent organ rejection. This non-specific immunosuppression affects their anti-viral immunity as well. We study qualitative and quantitative aspects of the immune response against respiratory viruses in kidney transplant recipients in collaboration with the Viroscience department of Erasmus MC. We also investigate whether virus-specific immunity can be used as a read-out of general immunosuppression in transplant recipients. Furthermore, we study the potential cross-reactivity of virus-specific T cells with allogeneic HLA, also known as heterologous immunity. We use cell culture systems, flow cytometry, and functional immune cell assays for these studies.
HLA- and non-HLA-specific T cells
Together with Michiel Betjes (internist-nephrologist EMC), we focus on the role of HLA- and non-HLA-reactive T cells in rejection and fibrosis in kidney transplant recipients. Using innovative techniques, we are able to in detail characterize at the single cell level, phenotype as well as function of (antigen-reactive) T cells within the circulation, allograft as well as using an in vivo human kidney organoid model to unravel mechanisms involved in rejection and fibrosis of the allograft. By studying the influence of recipient’s age on T cell alloreactivity we aim to facilitate personalized immunosuppressive medicine.
Kidney disease development and regeneration
Using patient-derived and control induced pluripotent stem cell-derived kidney organoids, we study the mechanisms of kidney disease development. Our studies include both genetic kidney disease and kidney injury induced by transplant-related insults. We developed a range of quantitative readouts to determine malformation, cellular injury and kidney fibrosis development. We are currently developing kidney organoids that contain induced pluripotent stem cell-derived macrophages and T cells to study the role of the immune system in kidney disease development.
Selected Publications
Chimeric HLA Antibody Receptor T Cells to Target HLA-Specific B Cells in Solid Organ Transplantation
Gille I, Hagedoorn RS, van der Meer-Prins EMW, Heemskerk MHM, Heidt S.
HLA. 2023;102(4):436-448.
DOI: 10.1111/tan.15146
PMID: 37370222
View publication on PubMed
Everolimus-Based Immunosuppression Induces Alloreactive Regulatory T Cell Expansion Combined with Loss of Alloreactive Effector T Cells
Litjens NHR, Jonker J, Klepper M, Prevoo F, Hesselink DA, Bemelman FJ, Nurmohamed SA, van Zuilen AD, Berger SP, Sanders J-SF, Betjes MGH.
Frontiers in Immunology. 2026;17:1904559.
DOI: 10.3389/fimmu.2026.1904559
View publication via DOI
Human Kidney Organoids Produce Functional Renin
Shankar AS, Du Z, Mora HT, van den Bosch TPP, Korevaar SS, van den Berg-Garrelds IM, Bindels E, Lopez-Iglesias C, Clahsen-van Groningen MC, Gribnau J, Baan CC, Danser AHJ, Hoorn EJ, Hoogduijn MJ.
Kidney International. 2021;99(1):134-147.
DOI: 10.1016/j.kint.2020.08.008
PMID: 32918942
View publication on PubMed
A Novel High-Throughput Droplet Digital PCR-Based Indel Quantification Method for the Detection of Circulating Donor-Derived Cell-Free DNA After Kidney Transplantation
Verhoeven JGH P, Boer K, Peeters AMA, Clahsen-van Groningen MC, Roodnat JI, van de Wetering J, Nieboer D, Bost DA, Baan CC, Hesselink DA.
Transplantation. 2022;106(9):1777-1786.
DOI: 10.1097/TP.0000000000004078
PMID: 35283452
View publication on PubMed
More Publications on PubMed
- Sebastiaan Heidt
View publications on PubMed - Martin Hoogduijn
View publications on PubMed - Nicolle Litjens
View publications on PubMed - K. Boer
View publications on PubMed
Erasmus MC
- Prof. dr. EJ. Hoorn, Dept. of Int. Med.
- Prof. dr. DA. Hesselink, Dept of Int. Med.
- Dr. M. Salih, Dept. of Int. Med.
- Prof. dr. LJW. van der Laan, Dept. of Surgery
- Dr. J. de Jonge, Dept. of Surgery
- Dr. RC. Minnee, Dept. of Surgery
- Dr. J. Mulder, Sophia Children Hospital
- Dr. TPP. van den Bosch, Dept of Pathology
- Dr. R. de Vries, Viroscience
- Dr. H. de Jong, Sophia Children Hospital
- Prof. dr. A.W. Langerak, Dept of Immunology
Outside Erasmus MC
- Prof. dr. MHM. Heemskerk, LUMC
- Dr. D. Roelen, LUMC
- Dr. A. de Vries, LUMC
- Prof. dr. F. Diekmann, Clínic Barcelona
- Prof. dr. R. Kramann, RWTH Aachen University
- Prof. dr. A. Zadpoor, Delft University of Technology
- Doug Bost, Jeta Molecular
- Attila Berces, Omixon Biocomputing
Our research is supported by a range of national and international funding programmes and collaborative initiatives.
Current and Recent Projects
PERMABO
Permanently Removing the ABO Barrier in Kidney Transplantation
Funding: Dutch Kidney Foundation, Creativity Grant
PERSIMMON
PERSonalized IMMunosuppression for ONe kidney for Life
Funding: NWO and Dutch Kidney Foundation
Chimeric HLA Antibody Receptor Therapy
A Promising Approach to Target HLA Sensitization
Funding: Dutch Kidney Foundation, Success Accelerator Grant
Organ Transplantation: Making Unsuitable Organs Suitable
A Transplantation Flagship Convergence programme focused on developing innovative approaches to improve the suitability of organs for transplantation.
Funding: Transplantation Flagship Convergence
Modelling Nephron Endowment in Multi-Hybrid Human Kidney Organoids
Research using advanced human kidney organoid models to study nephron development and kidney function.
Funding: Dutch Kidney Foundation, Creativity Grant
MiniMe
Allo-HLA and Non-HLA-Specific T Cells in the In Vivo Human Kidney Organoid Model: In Search of the Risky Cells for Allograft Function
Funding: Dutch Kidney Foundation, Success Kolff+ Accelerator Grant
TACMONOXL
A research collaboration focused on optimizing tacrolimus monotherapy after kidney transplantation.
Funding: Astellas and Dutch Kidney Foundation
