Research Projects

Host Institution: 

Department of Laboratory Medicine, Faculty of Medicine, Lund University

P1. Project Description

Title: 'Advancing Gene Therapies for Inherited Hematopoietic Disorders'

Theme: Invention & Innovation, Clinical Translation

Hematopoietic stem cell (HSC) gene therapy offers curative potential for inherited blood disorders, yet manufacturing bottlenecks, including rapid loss of stemness during ex vivo culture, inefficient transduction of long-term HSCs, limit clinical translation. This project addresses these challenges by developing novel small molecules to enhance HSC expansion and lentiviral transduction efficiency, potentially transforming ATMP manufacturing economics. 

This research directly supports RAMP-UP goals through its interdisciplinary design spanning medicinal chemistry, stem cell biology, and clinical manufacturing. The project unites academic partners (Lund University, Hannover Medical School, Chemical Biology Consortium Sweden) with industry leaders (Miltenyi Biotech), creating unique training opportunities across the ATMP value chain, from molecular tool development through CliniMACS Prodigy-based cell processing to regulatory considerations. 

By establishing patient-derived iPSC models for Diamond-Blackfan Anemia, this work bridges fundamental discovery to clinical validation, accelerating European ATMP implementation. The doctoral training encompasses translational competencies essential for next-generation ATMP scientists: understanding manufacturing constraints, navigating academic-industry partnerships, and connecting bench discoveries to bedside applications. Ultimately, by reducing gene therapy production costs and improving product quality, this research aims to democratize patient access to curative cellular therapies across Europe

 

Supervision

Main Supervisor: Agatheeswaran Subramaniam (Lund University)

Co‑Supervisors: Johan Flygare (Lund Stem Cell Center, Lund University), Axel Schambach (Hannover Medical School)

Secondment

The Doctoral Fellow will undertake a secondment at Miltenyi Biotec for a minimum of three months during Year 2. This placement, supervised by Dr. Eleni Papanikolaou, will provide hands-on training in clinical-scale HSPC processing using the CliniMACS Prodigy platform. The doctoral fellow will gain expertise in GMP-compliant manufacturing workflows, quality control procedures, and translational considerations critical for clinical implementation. This industry experience will enable direct integration of our small molecules developed in this project into clinical manufacturing pipelines, bridging academic innovation with industrial translation, a core objective of the RAMP-UP program

Keywords

Cell therapy manufacturing, Ex-vivo hematopoietic stem cell expansion, Inherited hematological disorders, Small molecules, Lentiviral gene therapy

Host Institution: 

Department of Experimental Medical Science, Faculty of Medicine, Lund University, 

P2. Project Description

Title: 'Induced Pluripotent Stem Cell (iPSC) derived mesenchymal stroma cell therapy to recover damaged donor lungs for transplantation'

Theme: Invention & Innovation, Clinical Translation

Lung transplantation is the only effective treatment for end-stage lung disease, but primary graft dysfunction remains a major cause of early mortality and chronic complications. Mesenchymal stromal cells (MSCs) offer therapeutic potential through tissue repair, anti-inflammatory effects, and cell survival. However, MSCs derived from somatic tissues vary in quality and lack standardization. Induced pluripotent stem cells (iPSCs) provide an optimal source for MSC production due to their unlimited expansion, differentiation capacity, and cryopreservation ability. iPSC-derived MSCs outperform traditional MSCs in reproducibility, homogeneity, and rejuvenation, and have shown promise in clinical trials for multiple conditions.

This PhD project aims to develop defined and reproducible high quality iPSC-derived MSCs for lung transplantation. Objectives include: (1) optimizing differentiation protocols, (2) characterizing MSCs using multiomics to ensure quality, (3) translating processes to GMP standards for clinical readiness, (4) testing MSC therapy in human lung models, (5) identifying predictive markers for efficacy using single-cell transcriptomics and AI. The project combines stem cell biology with clinical lung science; success could revolutionize lung availability and accelerate clinical translation, where secondment will be important to include aspects important for market access. The project will use available preGMP and GMP infrastructures and create CMC pipeline for iPSC derived cell therapies.

Supervision

Main Supervisor: Anna Falk (Lund Stem Cell Center, Lund University / LU - ATMP Centre)
Co‑Supervisor: Sandra Lindstedt (Lund University / Skåne University Hospital)

Secondments

There are several secondments that could be of interest for the project and beneficial for the doctoral fellow. Here are some suggestions: CCRM Nordic (SWE), Cellerator (DK), NothXBio (SWE), Bioneer (DK) which are infrastructures for process development and GMP manufacturing, the doctoral fellow would learn clinical translation, GMP manufacturing and automatization. Cellcolabs or Xintela, which are companies that manufacture MSC under GMP from bone marrow and fat, respectively, cells that would be good comparison material for this project’s iPSC derived MSC. Miltenyi, Biolamina and StemCell Technologies have interesting technologies and reagents that would be interesting for the doctoral fellow to learn more about.

Keywords

Cell therapy, Induced pluripotent Stem Cells, mesenchymal stroma cells, lung repair, clinical translation

Host Institution: 

Department of Experimental Medical Science, Faculty of Medicine, Lund University,

P3. Project Description

Title: 'Modelling Inhibitory Neuron Dysfunction in Psychiatric Disease for Therapeutic Discovery'

Theme: Invention & Innovation, Clinical Translation

Schizophrenia (SZ) affects more than 24 million people worldwide, yet there are still no treatments that directly target the biological causes of the disorder. Growing evidence suggests that problems in inhibitory interneurons—especially parvalbumin (PV) and somatostatin (SST) cells—play an important role by disrupting the balance between brain excitation and inhibition. However, the exact causes of interneuron dysfunction and differences between patients are still not well understood. This is partly because human inhibitory neurons are difficult to study, and animal models have important limitations.

This project aims to develop the first patient-derived interneuron model of SZ that accounts for individual differences. Clinical data, genetic information, and brain imaging measures will be combined to identify patients with clear signs of interneuron dysfunction. Induced pluripotent stem cells from these individuals will be used to generate PV and SST interneurons, which will then be grown in 3D cultures together with excitatory neurons. These models will be studied using electrophysiology and single-cell molecular analyses to uncover disease mechanisms and identify drug candidates that can restore normal network activity.

This project supports the goals of RAMP-UP by bringing together stem cell research, data analysis, and clinical neuroscience. It offers strong training opportunities for students from different scientific backgrounds and helps build skills that are useful in both academic and industry settings. By combining patient-based models with early drug testing, the project contributes to collaborative European research and supports the development of more precise and effective treatments for schizophrenia.

Supervisory Team

Main Supervisor: Daniella Rylander Ottosson (Lund Stem Cell Center, Lund University)

Co‑Supervisors: Alexander Frizell Santillo (Lund University), Kostantin Khodosevich (University of Copenhagen)

Secondments

Secondments are designed to give students a broad and exciting training experience across different research environments. Through academic placements, students will develop key analytical and computational skills, including single-cell data analysis at DTU and exposure to computational psychiatry at Aachen and Lund.

Hands-on experimental training will be provided during a secondment at DTU with Prof. Schoof, where students will learn advanced single-cell and proteomic techniques. In addition, a clinical secondment at European neuroimaging centers and a psychiatric hospital with Dr. Gaebler will introduce students to biomarker validation, patient stratification, and clinical trial design. Together, these experiences will help students understand how basic research can be translated into meaningful clinical impact.

Key Words

iPSC disease modelling, Schizophrenia stratification, Interneuron dysfunction, 3D neuronal cultures, Precision Therapeutics

Host Institution: 

Department of Laboratory Medicine, Faculty of Medicine, Lund University

P4. Project Description

Title: 'Harnessing Cellular Reprogramming to Generate Tumor‑Reactive T Cells'

Theme: Invention & Innovation, Clinical Translation

Tumor-infiltrating lymphocytes (TILs) targeting tumor antigens represent a powerful T-cell therapy; however, current expansion protocols yield limited numbers of tumor-reactive cells. This project integrates cancer-to-dendritic-cell reprogramming into TIL manufacturing to selectively expand tumor-reactive T-cells within a safe, scalable, and cost-effective clinical framework. Reprogrammed tumor cells generated from patient biopsies will be used to drive TIL expansion and to comprehensively characterize T-cell phenotype, antigen specificity, clonality, and tumor-killing activity in vitro and in vivo. These studies will culminate in the development of a GMP-compatible protocol for next-generation TIL products with enhanced tumor reactivity compared to current standard-of-care approaches. 

The project directly supports RAMPUP objectives by embedding doctoral training at the intersection of cellular reprogramming, regenerative medicine, cancer immunology, and ATMP manufacturing, equipping the next generation of researchers with end-to-end expertise spanning discovery to clinical implementation. It fosters a European translational ecosystem by integrating academic innovation with clinical GMP environments and industry-relevant development pipelines through a collaborative project with Asgard Therapeutics, spanning academia, industry, and healthcare. By addressing key manufacturing bottlenecks in personalized cell therapies, this work accelerates ATMP translation, improves patient access, and strengthens Europe’s leadership in next-generation cellular immunotherapies for solid tumors.

Supervision

Main Supervisor: Filipe Pereira (Lund Stem Cell Center, Lund University)
Co‑Supervisor: Fábio Rosa (Asgard Therapeutics AB)

Secondment

To strengthen the current proposal and enhance training outcomes, the doctoral fellow will benefit from a secondment opportunity of 6 months at Dr. Svane’s lab (HH, Denmark). This will ensure hands-on integration of DC reprogramming into the clinical manufacturing process at HH, and exposure to a clinical oncology setting. This will accelerate the project’s progress and support skill acquisition in cutting-edge methodologies, while consolidating strategic collaborations for advancing TIL therapy.

Keywords

Cell therapy, TIL immunotherapy, cellular reprogramming, Dendritic cell, T cell

Host Institution: 

Department of Experimental Medical Science, Faculty of Medicine, Lund University

P5. Project Description

Title: 'LUNG – REBOOT: Bioengineering a biomaterial-guided ATMP to reconstruct distal lung tissue'

Theme: Invention & Innovation, Clinical Translation

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death worldwide, is driven by chronic inflammation and aberrant epithelial repair, resulting in progressive alveolar destruction. This hostile microenvironment poses a major obstacle to cell-based therapies. We hypothesize that restoring key developmental extracellular matrix (ECM) cues—structural, biochemical, and mechanobiological—can reactivate regenerative programs required for alveolar repair.

We propose a strategy combining iPSC-derived distal tip epithelial progenitors with a bioengineered ECM microenvironment (BEM) designed to recreate core features of the developmental lung niche. Cells will be delivered within a protective, instructive BEM that restores signals lost in COPD, thereby enhancing survival, differentiation, and regenerative capacity. This PhD project will establish the core components needed to reconstruct the alveolar niche by:

1. Generating and validating iPSC-derived epithelial distal tip progenitor cells; and
2. Systematically rebuilding the lung microenvironment using a microfluidic platform that recapitulates lung architecture, airflow, and vascular support, ultimately yielding a physiologically relevant alveoli-on-chip model.

By harnessing developmental programs, this project aims to enable de novo alveolar formation in emphysematous lungs. It represents the starting point of a broader initiative to develop a bioengineered advanced therapy product (ATMP) for COPD, providing the foundational components for future translational steps.

Supervision

Main Supervisor: Gunilla Westergren‑Thorsson (Lund University)
Co‑Supervisors: Mattias Magnusson (Lund Stem Cell Center, Lund University), Niels Bent Larsen (Technical University of Denmark)

Secondments

The doctoral fellow will regularly work at DTU with optimization of the BEM with the co-applicant Prof. Bent Larsen. A non-academic secondment will be planned with either AstraZeneca (Gothenburg) or Cantargia AB (Lund) focusing on QTPP/CCQA definition and potency assay translation. 

Keywords

Bioengineered ECM microenvironment (BEM), iPSC, Alveolar regeneration, Microfluidic platform, Chronic obstructive pulmonary disease (COPD)

Host Institution: 

Department of Experimental Medical Science, Faculty of Medicine, Lund University

P6. Project Description

Title: 'Inflammation‑Regulated Gene Therapy for Neurological Disorders'

Theme: Invention & Innovation, Clinical Translation

Diseases of the central nervous system (CNS) impose a significant societal and economic burden, yet effective disease-modifying therapies are scarce. Gene-based advanced therapy medicinal products (ATMPs) show great promise, but current approaches often lack the necessary cellular, and disease-state specificity to be effective and safe. The goal of this project is to overcome these limitations by developing next-generation gene regulatory strategies that enable precise, inflammation-responsive transgene expression. 

Based on recent findings from our lab showing that transposable elements (TEs) are activated in a cell-type-specific manner in response to interferon signaling in Parkinson’s disease, this research will exploit TE biology to engineer novel synthetic gene regulatory elements (GREs). 

Using human induced pluripotent stem cell–derived microglia, astrocytes, and dopaminergic neurons combined with immune stimulation, multi-omics profiling, and longread epigenetic sequencing, the project will identify TE promoters that are activated in a cell-type- and inflammation-dependent manner. Machine learning will then be used to design minimal synthetic GREs capable of directing controlled transgene expression. These elements will be tested in viral vectors in vitro, and selected candidates will advance toward in vivo validation. 

This project has the potential to substantially improve CNS-targeted ATMPs and contribute to more precise, effective, and translatable therapeutic strategies. 

Supervision

Main Supervisor: Johan Jakobsson (Lund Stem Cell Center, Lund University)
Co‑Supervisor: Malin Parmar (Lund Stem Cell Center, Lund University)

Secondments

The research plan includes secondment opportunities at international partner laboratories such as the ASAP consortium for extended omics data integration experience, and at Industry partners or manufacturing sites for exposure to industrial-scale gene therapy vector production. These placements will expand the doctoral fellow’s network and technical skill set, directly supporting project objectives.

Keywords

Gene therapy, Viral Vectors, Gene Regulatory Elements, Transposable Elements, Inflammation

Host Institution: 

Department of Experimental Medical Science, Faculty of Medicine, Lund University

P7. Project Description

Title: 'Understanding Transcriptional Regulation for the Generation of Dopamine Neurons: A Perturb‑Seq Approach for Stem Cell Therapy in Parkinson’s Disease'

Theme: Invention & Innovation, Clinical Translation

This project supports RAMP-UP goals and ATMP relevance by advancing regenerative medicine focused on dopaminergic neuron generation for Parkinson's Disease (PD) stem cell therapies. The project fosters innovation critical for Europe to maintain global leadership in advanced therapies by integrating molecular biology, computational modeling, and CRISPR-based functional genomics into the translational pathway. 

Embedded at Lund University within a collaborative network of leading academic groups, healthcare providers, regulatory bodies, and industrial partners across Europe, the program helps build a coherent European education ecosystem. This environment ensures both deep scientific expertise and a broad understanding of the interdisciplinary landscape, thus training expertise across the ATMP value chain from basic discovery to clinical application. 

By refining stem cell differentiation protocols to improve yield, safety, and efficacy of dopamine neuron progenitors, the project bridges bench-to-clinic gaps in regenerative neurology and stem cell therapy. Insights gained will enhance product quality, manufacturing reproducibility and therapeutic outcomes, addressing key bottlenecks in the production of cell-based ATMPs for PD that can be broadly applied also to other diseases.

In sum, this PhD project embodies RAMP-UP's mission by providing innovative and interdisciplinary training in regenerative medicine and ATMPs, positions the candidate within a European ecosystem that connects academia, healthcare, regulators, and industry.

Supervisory Team

Main Supervisor: Malin Parmar (Lund Stem Cell Center, Lund University)
Co‑Supervisor: Petter Storm (Lund University)

Secondments

The research plan includes secondment opportunities at international partner laboratories such as the ASAP consortium for extended single-cell data integration experience, and at Industry partners or manufacturing sites for exposure to industrial-scale cell differentiation CRISPR library design, and advanced genomic applications. These placements will expand the doctoral fellow’s network and technical skill set, directly supporting project objectives.

Key Words

Dopamine Neurons, Stem Cell Therapy, Pluripotent Stem Cells, Perturb‑Seq, Computational Modeling

Host Institution: 

Department of Immunotechnology, Faculty of Engineering, Lund University

P8. Project Description

Title: 'Function focus in development of Chimeric Antigen Receptor (CAR)‑based therapy'

Theme: Invention & Innovation, Clinical Translation

The project will focus on antibody development with high throughput functional screening to identify constructs for Chimeric Antigen Receptor (CAR) based treatment in oncological disease. It will integrate early target discovery data, with high throughput antibody generation capability and unique screening technologies to achieve the goal of discovering constructs for translation to clinical implementation.

The doctoral fellow’s project will generate methodologies, technologies, and data suitable for collaboration between medical and technical faculties and for collaboration with pre GMP and GMP production facilities at Lund University and Region Skåne. A clinical co supervisor and planned secondments will provide a great intersectoral environment for the doctoral fellow to grow into the future leader in the field. Knowhow, processes, and tools will be made available to the wider research community through the Swedish national research infrastructure SciLifeLab Drug Discovery and Development Platform.

Supervisory Team

Main Supervisor: Mats Ohlin (Lund University)
Co‑Supervisors: Sara Ek (Lund University), Mats Jerkeman (Lund University)

Secondments

Skåne University Hospital GMP facility for insight into GMP production requirements; The Swedish Medical Products Agency for insight into regulatory requirements; CCRM Nordic for insight into process and analytical development, and GMP production.

Key Words

Chimeric Antigen Receptor, CAR‑T development pipeline, Functional screening, Bispecific construct, lymphoma/leukemia

Host Institution: 

Department of Clinical science/Cardiothoracic surgery, Faculty of Medicine, Lund University

P9. Project Description

Title: 'Reconditioning Discarded Donor Lungs with Next‑Generation Engineered iMSCs: A Translational ATMP Platform for Lung Transplantation'

Theme: Invention & Innovation, Clinical Translation

Lung transplantation (LTx) is the only curative option for many patients with end-stage lung disease. Yet it is constrained by a high discard rate of donor lungs due to acute injury and by primary graft dysfunction (PGD), a leading cause of early post-transplant mortality. There is no targeted therapy to reliably repair injured donor lungs or prevent ischemia-reperfusion injury (IRI)-driven PGD. This hands-on doctoral project will develop induced pluripotent stem cell-derived mesenchymal stromal cell (iMSC) advanced therapy medicinal products (ATMPs) that are engineered for enhanced potency and immune compatibility (i.e., mitochondrial enrichment, hypoimmunogenicity, and additional immunomodulation). 

In this interdisciplinary, multisector collaboration across Sweden and Germany, the PhD candidate will: 

1. generate and validate engineered iMSCs using mechanism-linked potency assays; 
2. establish scalable, GMP-aligned manufacturing and release criteria; and, 
3. test efficacy and safety in clinically relevant mouse and porcine LTx/ex vivo lung perfusion settings and human lung models. 

The project directly supports RAMP UP goals by training the candidate across the ATMP value chain, from discovery and design, through GMP production and quality systems, to translational development with academic, healthcare, and industry stakeholders, thus accelerating readiness for first-in-human studies and strengthening Europe’s capacity to deliver regenerative ATMPs to patients

Supervisory Team

Main Supervisor: Sandra Lindstedt (Lund Stem Cell Center, Lund University)
Co‑Supervisors: Franziska Olm (Lund University), Constança Sofia Ferreira de Figueiredo (Hannover Medical School)

Secondments

During a 1-month stay at Miltenyi Biotec (DE) as a visiting doctoral fellow, planned for Q4 2026 or Q1 2027, the candidate will learn how to use their automated CliniMACS Prodigy platform to enable process transfer to Lund, allowing us to produce the initial batches of this off-the-shelf ATMP and providing the fellow with valuable insights into the life science industry. Over 3 months at Hannover University, the fellow will be trained on the short hairpin silencing methods for WP1 to create HLA-deficient hypoimmunogenic iMSCs.

Key Words

Lung transplantation, Ex-vivo organ perfusion, Genetic engineering, iPSC‑derived MSCs, ATMP development

Host Institution:

Department of Experimental Medical Science, Faculty of Medicine, Lund University

P10. Project Description

Title: 'Cell‑Selective Gene Delivery to Restore Vascular Smooth Muscle Function in Ageing Vessels'

Theme: Invention & Innovation, Clinical Translation

This project addresses the lack of regenerative strategies for vascular disease by targeting age-dependent dysfunction in vascular smooth muscle cells (VSMCs). Reduced YAP/TAZ activity has been implicated in vascular inflammageing and loss of VSMC phenotypic stability. The project will test VSMC-selective gene delivery as a basis for vascular advanced therapy medicinal products (ATMPs), using established models of vascular ageing, atherosclerosis, and vein-graft disease, with validation in organ-cultured intact human vessels. 

The project contributes to RAMP-UP’s objective of interdisciplinary doctoral training by combining vascular biology, gene therapy, advanced imaging, and translational research within a single PhD program. The doctoral candidate will gain experience spanning target identification, vector design and delivery, in vivo and ex vivo disease models, and data integration. 

The work is embedded in a European research environment linking Lund University, Leiden University Medical Center, and the MAX IV Laboratory. This structure integrates academic research, clinical vascular surgery, large-scale imaging infrastructure, and industrial ATMP expertise, supporting cross-sectoral training and knowledge exchange. 

To support translation and future patient access, the project focuses on clinically relevant local gene-delivery strategies and incorporates considerations related to vector scalability, manufacturability, and regulatory pathways through interaction with industrial partners. This approach connects mechanistic discovery with realistic ATMP development in a European context.

Supervision

Main Supervisor: Sebastian Albinsson (Lund University)

Co‑Supervisors: Margreet de Vries (Leiden University Medical Center), Karl Swärd (Lund University)

Secondments

A 6-month secondment at Leiden University Medical Center with Margreet de Vries, PhD, (in 2027) will provide in-depth training in vein-graft models and photoacoustic imaging. In addition, short visits to the RAMP-UP associated partner NorthX Biologics and to national infrastructures such as MAX IV or SciLifeLab will provide exposure to AAV manufacturing, regulatory considerations, and advanced imaging and spatial transcriptomics.

Keywords

AAV-mediated gene delivery, Vascular smooth muscle, Vascular ageing, Atherosclerosis, YAP/TAZ-dependent transcriptional regulation

Host Institution: 

Department of Laboratory Medicine, Faculty of Medicine, Lund University

P11. Project Description

Title: 'Transplantation of gene‑repaired hematopoietic stem cells as novel treatment for myelofibrosis'

Theme: Invention & Innovation, Clinical Translation

Myelofibrosis (MF) is one of the most severe hematopoietic stem cell (HSC) malignancies. Allogeneic stem cell transplantation (allo-HSCT) is currently the only curative option, but most MF patients are ineligible due to advanced age and the high risk of treatment related mortality. Autologous HSC transplantation (auto-HSCT) is less intensive and suitable for older patients, but MF HSCs carry disease driving mutations. Therefore, a successful autologous strategy requires transplantation of genetically corrected HSCs. 

This doctoral project aims to develop a novel, potentially curative approach to MF therapy through ex vivo gene repair of MF HSCs. We will establish optimized CRISPR Cas–based correction of MF HSCs using a novel acoustic trapping gene transfer platform, followed by ex vivo expansion to generate sufficient HSCs for transplantation. The functional potential of the expanded HSCs will be assessed using our unique MF xenotransplantation model. 

The ultimate goal is to develop an Advanced Therapy Medicinal Product (ATMP) for clinical application in MF, integrating age adapted conditioning, autologous transplantation of expanded, gene corrected stem cells, and post-transplant strategies to target minimal residual disease.

Supervisory Team

Main Supervisor: Stefan Scheding (Lund Stem Cell Center, Lund University)
Co‑Supervisors: Niklas Landberg (Lund University), Hongzhe Li (Lund University)

Secondments

1. AcouSort AB (co-founder Scheding): provides training in acoustic cell and particle handling.
2. Biolamina AB: optimized and automated ex-vivo expansion systems

Key Words

Myelofibrosis, GTMP, gene therapy medicinal product, ex‑vivo gene repair and stem cell expansion, Acoustic trapping‑enhanced gene transfer, ATMP xenotransplantation models

Host Institution: 

Department of Clinical Sciences, Faculty of Medicine, Lund University

P12. Project Description

Title: 'Brain repair after stroke by new reprogrammed neurons and oligodendrocytes'

Theme: Invention & Innovation, Clinical Translation

Cortical ischemic stroke disrupts interhemispheric interaction because of death of transcallosal projection neurons (TCPNs) connecting corresponding cortical regions. These connections usually facilitate integration of sensory, motor, and cognitive functions. We hypothesize that stroke recovery can be improved by:

1. restoring lost interhemispheric communication through the transplantation of new TCPNs and,
2. promoting remyelination of stroke-damaged axons and axons of grafted neurons via oligodendrocyte (OL) transplantation, with both cell types derived from human induced pluripotent stem cells. 

First, we will develop an efficient method to produce humaninduced TCPNs (hiTCPNs) and OLs (hiOLs) with myelination capacity as ATMPs. Next, we will validate a new approach for reconstructing cortical networks by simultaneously transplanting hiTCPNs and hiOLs in animal model of ischemic stroke. To move this method toward clinical application, we will use a microfluidic chip-based ex vivo system for focal ischemic stroke using postsurgical human brain tissue, allowing the assessment of these ATMPs in an allotransplantation setting (human cells to human tissue). 

Our innovative, interdisciplinary doctoral program is designed to promote bridging of bench and clinic. While combining ATMP development with new regenerative medicine strategies based on co-transplantation, it will train PhD students across key areas of modern biomedical and translational research.

Supervisory Team

Main Supervisor: Zaal Kokaia (Lund Stem Cell Center, Lund University)

Co‑Supervisor: Sara Palma‑Tortosa (Lund University)

Secondments

To strengthen doctoral training and translational impact, planned secondment opportunities are with academic partners specializing in neuroimaging (current collaborator Markus Aswendt, Goethe University Frankfurt) and advanced analysis of neuronal network data (current collaborators Daniel Tornero (Barcelona University) and Zoltan Molnar (Oxford University)). These secondments will broaden methodological expertise, expand international networks, and support career development.

Key Words

Stem cell, Reprogramming, Ischemic stroke, Transcallosal Projection Neurons, Regeneration

Host Institution: 

Hannover Medical School

P13. Project Description

Title: 'iPSC-derived and CAR-enhanced natural killer cells as an advanced off-the-shelf technology to treat autoimmune diseases'

Theme: Invention & Innovation, Clinical Translation, Commercialisation, Ethical, Legal, and Social Implications (ELSI)

Autoimmune diseases (AID) are considerable medical problems as they involve the immune system, which attacks the own body, causing chronic inflammation, organ damage, and potentially life-threatening complications, with AID affecting ~ 1 in 10 people. 

Very recently, novel gene- and cell-based strategies were developed to use chimeric-antigen-receptor-equipped autologous T cells to deplete the autoreactive B cells in patients and to reprogram their immune repertoire back into a healthy one as a groundbreaking and long-lasting cure. 

Here, we built upon these successes by developing an off-the-shelf strategy that is less likely to cause cytokine release syndrome and might be even better tolerated. We aim to generate broadly applicable off-the-shelf NK cells from human induced pluripotent stem cells (hiPSC) targeted to deplete B cells in patients. iPSC will be equipped with state-of-the-art NK chimeric-antigen-receptors, offering a tailored approach to deplete B cells and autoimmunity. 

This project is based on an existing collaboration with Lund University (Niels-Bjarne Woods) and ideally fits into the scope of RAMP-UP, creating an innovative, interdisciplinary project and contributing to a European educational ecosystem to create iPSC-based immunotherapeutics as novel off-the-shelf ATMPs for patients in urgent need.

Supervisory Team

Main Supervisor: Axel Schambach (Hannover Medical School)

Co‑Supervisor: Hildegard Büning (Hannover Medical School), Niels Bjarne Woods (Lund Stem Cell Center, Lund University)

Secondments

We plan an intense collaboration with the Woods lab at Lund University. A 2nd secondment is planned in the Lund University ATMP Center to learn more about the further translation of the established technology in GMP labs and the scaling to clinical trials.

Key Words

Gene therapy, ATMPs, iPSC‑derived cell transplants, CAR‑equipped natural killer (NK) cells, autoimmune diseases.

Host Institution: 

Hannover Medical School

P14. Project Description

Title: 'Novel gene therapy approaches for Diamond-Blackfan Anemia'

Theme: Invention & Innovation, Clinical Translation 

Gene therapy represents a new curative treatment option for several monogenetic defects of the blood and immune systems, as shown for severe combined immunodeficiencies, globinopathies, metabolic diseases, and aplastic anemia. The team has translated several of these discoveries from bench to bedside, e.g., for babies with severe combined immunodeficiencies, and also using CAR-T approaches for different cancer settings. 

Moreover, together with Johan Flygare (Lund), we have recently developed a gene therapy for Diamond-Blackfan Anemia (DBA) that could potentially serve as a curative treatment, addressing its life-threatening nature and limitations of current therapies (like frequent transfusions/iron overload) by correcting the underlying genetic defect. 

Here, using the principles learned, we aim to extend this novel and groundbreaking strategy to treat other DBA forms to form a broad basis for proof-of-concept to treat all children with DBA. This project will develop novel and state-of-the-art lentiviral vectors for the genetic correction of the underlying disease and validate efficacy and safety in disease-relevant modeling systems. 

Thus, this proposal will create an international EU-based innovative ATMP platform and educational ecosystem for DBA, translating these novel treatment options to patients in need.

Supervisory Team

Main Supervisor: Axel Schambach (Hannover Medical School)

Co‑Supervisor: Johan Flygare (Lund Stem Cell Center, Lund University), Martin Sauer (Hannover Medical School)

Secondments 

A strong collaboration with the Flygare lab in Lund is planned and a secondment in his lab is planned to validate the new gene therapy vectors generated at MHH. Further secondments are envisioned at Miltenyi Biotec /Lentigen (producer of the previous GMP batch for rps19-dependent DBA) and Novo Nordisk.

Key Words

Gene therapy, ATMP, translation, Diamond‑Blackfan anemia, ribosomal proteins.

Host Institution: 

Institute of Experimental Hematology, Hannover Medical School

P15. Project Description

Title: 'Designer Macrophages: Modular, Target-Responsive iPSC-Derived Macrophages for Neurodegenerative Disorders'

Theme: Invention & Innovation

Genetic engineering to express chimeric antigen receptors (CARs) in induced pluripotent stem cell (iPSC)- derived macrophages opens new therapeutic avenues, particularly for neurodegenerative diseases, such as Alzheimer's disease (AD). In AD, accumulation of Amyloid Beta (Aβ) is a key driver for chronic neuroinflammation and microglial dysfunction, accelerating neuronal loss and disease progression. Central nervous system (CNS) infiltration, long-term persistence, clearance of pathological protein aggregates, and dynamic immunomodulation are crucial for an effective therapy targeting the multifactorial nature of AD. 

In this project, we will develop iPSC-derived designer-Macrophages that combine CAR-mediated uptake of pathological targets with modulation of neuroprotective and anti-inflammatory factors directly at the site of disease. This multifactorial, target-responsive approach aims to restore neuroimmune balance, enhance neuronal protection, and overcome limitations of current single-target therapies. 

The project directly supports the RAMP-UP mission by training doctoral researchers at the interface of regenerative medicine, synthetic immunology, and ATMP development, while combining clinical, academic and industrial expertise. By advancing a scalable, modular, and clinically transplantable CAR-Macrophage platform, this work contributes to accelerating ATMP implementation and improving patient access to innovative therapies across Europe.

Supervisory Team

Main Supervisor: Lucas Lange (Hannover Medical School)

Co‑Supervisor: Søren Skov (University of Copenhagen), Axel Schambach (Hannover Medical School)

Secondments

Two focused secondments will complement the project’s experimental and translational goals. Miltenyi Biotec could provide expertise in myeloid cell processing, GMP-compatible workflows, and scalable manufacturing, supporting differentiation optimization, and GMP-compliant CAR-Macrophage production. CCRM Nordic could offer training in ATMP development, regulatory pathways, and early clinical translation, strengthening the candidate’s understanding of ATMP classification, documentation, and trial planning. These placements would provide complementary technical and translational skills essential for advancing designer macrophages toward clinical application

Key Words

iPSC-Macrophages, Chimeric Antigen Receptors (CAR), Cell Therapy, Neurodegeneration

Host Institution:  

nstitute of Experimental Hematology, Hannover Medical School

P16. Project Description

Title: 'Development of novel CAR-T and CAR-NK cells against cancer'

Theme: Invention & Innovation

Advances in immune therapies are reshaping paradigms of modern medicine. Engineered cell therapies such as chimeric antigen receptor (CAR)-modified T and natural killer (NK) cells showed efficacy against several types of B-cell malignancies. However, these advanced therapy medicinal products (ATMPs) were thus far less effective against solid cancers like pancreatic ductal adenocarcinomas (PDAC). 

Here, we will generate novel cell therapies using state-of-the-art vector systems that incorporate TRUCK (T cells redirected for antigen-unrestricted cytokine-initiated killing) principles to combine the targeting capacity of CARs with an inducible gene expression cassette to redirect immune cell cytotoxic activity for improved elimination of tumor cells, such as PDAC. 

This project will contribute to the current European initiatives to generate and translate novel gene and cell therapies. The student working on this project will gain expert knowledge on design and use of clinically applicable retroviral vectors, state-of-the-art cell modification technologies and assays to assess immune cell activity. Our close collaboration with clinical experts will help further strengthen the translation of research results to clinical use. Thus, this interdisciplinary project will have a real clinic to bench to clinic character, which keeps delivery of newly developed ATMPs to the patient as a central goal.

Supervisory Team

Main Supervisor: Michael Morgan (Hannover Medical School)

Co‑Supervisor: Thomas Wirth (Hannover Medical School), Linda Feldbrügge (Hannover Medical School)

Secondments

A secondment at Miltenyi Biotec to gain experience in how GMP vectors for clinical use are produced would support student development and translation of this project.

Key Words

Gene and cell therapy, T cells, Natural Killer (NK) cells, Chimeric Antigen Receptor (CAR) technology, cancer

Host Institution:  

Institute of Experimental Hematology, Hannover Medical School

P17. Project Description

Title: 'Understanding clonal dynamics in gene therapy trials'

Theme: Clinical Translation

Retroviral gene therapy is a life-saving treatment for patient with inborn errors of the immune system lacking a suitable donor, but it can trigger insertional oncogenesis. In early clinical trials with gammaretroviral vectors, insertional mutagenesis induced oncogenesis. In one trial, eight out of nine patients developed leukemia. Integration site analysis (ISA) was not able to predict the onset of leukemia at that time. Even in a current clinical trial using a lentiviral vector, ISA monitoring failed to predict the onset of clonal imbalance. The field needs a better understanding of which parameters precede clonal imbalance.

We will use a state-of-the-art integration site analysis pipeline to study a unique longitudinal sample collection from the past Wiskott-Aldrich trial (DRKS00000330). We will investigate when malignant clones first emerge and which compartments best predict danger. We will recreate patient-specific high-risk insertions via guided integration to dissect early clonal kinetics and cooperating mutations in vitro models. 

Finally, we will build quantitative reference standards to calibrate ISA pipelines across labs. We aim to enable early clonal detection, mechanistic insight, and robust monitoring across trials, reducing leukemia risk while preserving therapeutic benefit.

Supervisory Team

Main Supervisor: Michael Rothe (Hannover Medical School)

Co‑Supervisor: Steven Talbot (Hannover Medical School), Erik van den Akker (Leiden University Medical Center)

Secondments

We are using the Stem Span medium for the expansion of hematopoietic stem and progenitor cells and the guided insertional mutants. Hence, a secondment at StemCell Technologies would be a great fit. Furthermore, the external co-supervisor Prof. van den Akker already signaled his approval to host the student for a secondment at his lab to teach crucial bioinformatic techniques.

Key Words

Product safety of integrating viral vectors, integration site analysis, monitoring of gene therapy trials.

Host Institution: 

Department of Cell and Chemical Biology, Leiden University Medical Center

P18. Project Description

Title: 'Beta-cell destruction in type 1 diabetes: when sweetness fails'

Theme: Invention & Innovation, Clinical Translation

Type 1 diabetes (T1D) results from the specific destruction of insulin producing beta-cells by autoreactive T-cells. While the hyperexpression of HLA molecules at the surface of beta-cells represents the hallmark of T1D, the TCR-HLA class I molecular interactions driving CD8-mediated cell destruction is tightly regulated by cell surface sugar moieties that fine-tune the strength and specificity of the immunogenic response. 

In cancer, the modulation of surface neolacto-series, shielding immune cell receptors, is an established mechanism, identified as key component in tumor evasions. Learning from tumor immunology, we anticipate that such processes are disturbed during type 1 diabetes development, increasing beta-cell visibility to immune cells and precipitating beta-cell destruction. 

By bridging critical synergetic expertise in immunology, glycobiology, regenerative medicine, with cutting-edge technologies, this project aims at establishing the glycomic profile of insulin-producing cells and at determining the impact of T1D pathophysiological conditions on the beta cell surfaceome to advance our understanding of the development of autoimmunity. 

Exploring these processes will provide new insight into the T1D pathology and offer novel stealth approaches for advanced therapy medicinal products, to protect iPSC-derived beta-cells from autoimmune rejection in T1D, and other stem cell products for regenerative therapies.

Supervisory Team

Main Supervisor: Arnaud Zaldumbide (Leiden University Medical Center)

Co‑Supervisor: Francoise Carlotti (Leiden University Medical Center), Marie-José Goumans (Leiden University Medical Center)

Secondments

The project will benefit from the geographic embedding of the LUMC within the bioscience park Leiden but also labs and expertise present at the Faculty of Science of Leiden University.

A 3 to 6 months internship period will be planned at the Stem Cell Technology for Microphysiological Modelinggroup headed by Prof. Micha Drukker and Image-based Computational Biology group headed by Dr. Joost Beltmanat the Leiden Academic Center for Drug Research (https://www.universiteitleiden.nl/en/science/drug-research) for real time monitoring of islet function, immune cell infiltration and T cell mediated destruction.

Key Words

Autoimmunity, beta cells, stealth technology, glycosylation, pluripotent stem cells.

Host Institution:  

Department of Immunology,Leiden University Medical Center

P19. Project Description

Title: 'Human iThy-organoids restore T cell immunity in thymus-deficient patients'

Theme: Invention & Innovation

The thymus is the primary lymphoid organ for the development of hematopoietic progenitor cells into mature T-cells, and thus responsible for T-cell immunity. Thymic epithelial cells are essential for the selection of T-cells that can recognize a wide range of foreign antigens and are tolerant to self-antigens. 

Patients born without a thymus (~1:400,000) lack functional peripheral T-cells and die early in life from recurrent infections, if left untreated. Novel cellular therapies are urgently needed, as the only available treatment involves transplantation of scarce allogeneic donor tissue, carrying risks of rejection and autoimmunity. 

A promising strategy for thymic regeneration involves the use of human induced pluripotent stem cells (hiPSCs). Using autologous hiPSC sources to generate induced thymic epithelial progenitor cells (iTEPCs), we ultimately aim to generate thymic (iThy) organoids as cellular treatments to restore T-cell immunity. Differentiation into iTEPCs for the generation of fully functional thymus organoids has not been successfully established and would add innovation to regenerative medicine and ATMP development. 

To advance our experience with differentiating iPSCs into iTEPCs, we will test differentiation factors including potential supporting 3D-scaffolds and/or clinically suitable feeder cells, while anticipating future regulatory requirements. iThy organoids will be tested in vitro and in humanized NSG-nude (athymic) mice for the generation of functional T-cells with a polyclonal repertoire

Supervisory Team

Main Supervisor: Kirsten Canté (Leiden University Medical Center)
Co‑Supervisors: Frank J.T. Staal (Leiden University Medical Center)

Secondments

Prof. Robert Zweigerdt (Hannover) has expressed his commitment and agreed to collaborating. He has extensive experience in hiPSC-organoid models reflecting heart, foregut and hematopoiesis development. We envision a mutual beneficial exchange of experience in further developing our hiPSC-derived thymic organoid as well as sharing hiPSC-derived T- and B-cell differentiation in in vitro models.

Key Words

Thymic organoids, Human induced pluripotent stem cells, T cell development, T cell immunity, Cellular therapy

Host Institution: 

Department of Anatomy and Embryology, Leiden University Medical Center

P20. Project Description

Title: 'Repair-Independent Gene Integration in Patient-Derived Human HSPCs for Immune Correction of ZIP7 Deficiency'

Theme: Invention & Innovation

Advanced Therapy Medicinal Products (ATMPs) are increasingly driven by next-generation genome-engineering technologies that allow safe, precise, and efficient gene integration in human cells. EvoCAST, an engineered CRISPR-associated transposase system, enables programmable, template-free DNA integration, overcoming key limitations of conventional CRISPR-Cas-based genome editing in hematopoietic stem and progenitor cells (HSPCs). This repair-independent approach is particularly well-suited for inborn errors of immunity (IEI), where broad genetic diversity makes mutation-specific strategies difficult to scale.

This PhD project will establish EvoCAST-mediated gene integration in patient-derived human HSPCs and deliver a mechanistic understanding of the factors that determine transposition efficiency, integration precision, and stem-cell fitness. The candidate will optimize delivery and transposition parameters, then systematically map integration outcomes, and assess genomic safety using targeted assays and genome-wide sequencing. Together, these studies provide a strong, career-building platform at the interface of advanced genome engineering, stem cell biology, and translational safety assessment for ATMP development.

To directly link editing outcomes to therapeutic function, the project will use ZIP7 deficiency, a disorder characterized by a complete block in B-cell development, as a disease model. EvoCAST-edited HSPCs will be evaluated for on-target integration, integration fidelity, and functional rescue using established differentiation assays and disease-relevant models. After proof of concept, the EvoCAST–HSPC framework can be expanded to additional IEI, enabling scalable, mutation-independent ex vivo strategies with broader clinical impact.

By integrating molecular biology, clinical immunology, and translational assay development, this project supports RAMP-UP’s training objectives and aims to establish a CRISPR-associated transposase-based gene-integration paradigm in primary human HSPCs, with transformative potential for next-generation immune ATMPs.

Supervisory Team

Main Supervisor: Prarthana Mohanraju (Leiden University Medical Center)
Co‑Supervisors: Lisa Ott de Bruin   (Leiden University Medical Center), Niels Geijsen (Leiden University Medical Center)

Secondments

An optional 1–6-month secondment has been mutually agreed with Prof. Dr. Axel Schambach’s laboratory at Hannover Medical School (MHH), with the exact timing and scope to be defined. His group specializes in gene therapy–associated mutagenesis and would provide hands-on training in off-target profiling and genomic stability assays, strengthening the translational evaluation of EvoCAST in HSPCs.

Key Words

Genome editing, Inborn Errors of Immunity (IEI), CRISPR associated transposase (CAST), Hematopoietic Stem and Progenitor Cells (HSPC), Mutation independent gene integration

Host Institution:

Department of Immunology, Leiden University Medical Center

P21. Project Description

Title: 'Engineering Lentiviral Vectors for Precise Gene Expression to Improve Safety of Hematopoietic Stem Cell Gene Therapy'

Theme: Invention & Innovation, Clinical Translation

Rare genetic diseases affect more than one million people in the Netherlands and lack curative treatments. Gene therapy targeting hematopoietic stem and progenitor cells (HSPCs) offers the potential for durable, possibly one-time cures for inborn errors of immunity (~1:1,000-5,000 prevalence), as corrected stem cells sustain lifelong tissue renewal. This strategy has already proven lifesaving in infants with RAG1-deficient severe combined immunodeficiency (SCID). Current lentiviral (LV) vectors provide limited control over transgene expression, raising safety concerns such as insertional oncogenesis and highlighting the need for safer vector designs.

 This project aims to develop next-generation LV vectors that enable cell-type-specific and temporally regulated gene expression by incorporating endogenous gene regulatory sequences (GRS). Combining single-cell multi-omics, human bone marrow and thymus organoids, CRISPR-based functional validation, and iPSC-derived disease models, the project will engineer and validate GRS-containing LV vectors for precise and safe genetic correction of HSPCs. In vivo xenotransplantation and genotoxicity studies will support translational readiness. The approach is expected to be readily transferable to CRISPR-Cas9 gene-editing strategies, enabling regulated transgene expression from safe harbor loci.

Supervisory Team

Main Supervisor: Sander de Kivit (Leiden University Medical Center)

Co‑Supervisors: Karin Pike‑Overzet (Leiden University Medical Center), Frank J.T. Staal (Leiden University Medical Center)

Secondments

Prof. Johan Flygare (Lund University; design erythroid/myeloid-specific vectors) and Dr. Michael Rothe (Hannover Medical School; LV vector safety assessment) have expressed their willingness to offer secondments. Our groups have extensive and complementary expertise in HSPC-based gene therapy development. Through these secondments, we will strengthen our collaborations and exchange expertise to establish an internationally acknowledged network of excellence in ATMP development, with a focus on HSPC-based therapies.

Key Words

Hematopoietic stem and progenitor cells, Gene therapy, Lentiviral vectors, Gene regulation, Inborn errors of immunity