PhD in cell therapy for hereditary eye diseases: A vision for the future

Developing new treatments starts with models that accurately reflect the disease in the patient. In this four-year PhD project, you will develop and characterize new patient-based preclinical models, both in vitro and in vivo, for inherited retinal diseases, including gyrate atrophy and retinitis pigmentosa. Using these models, you will investigate disease mechanisms and evaluate the potential of cell therapy.

You will work with patient-derived stem cells and develop and optimize differentiation protocols for relevant retinal cell types and tissue models. You will characterize how patients' genetic and clinical characteristics are reflected in the morphology, molecular properties and function of these models. In addition, you will work on the development and characterization of patient-based in vivo models. By connecting findings from cell and tissue models, in vivo models and clinical practice, you will investigate which models and outcome measures are suitable for evaluating new treatments.

These model systems will subsequently form the basis for preclinical cell therapy research. You will investigate how stem cell-derived cells and biomaterials can be combined to create transplantable cell constructs and evaluate their survival, integration and function after transplantation.

The project connects Platform A: Model systems and Pillar 3: Cell-based therapy of the Lifelong VISION consortium. The development of relevant disease models and the development of cell therapy therefore go hand in hand. Through the Emma Center for Personalized Medicine (Emma CPM), the research aligns with the broader ambition of connecting diagnostics and therapy development for rare hereditary diseases.

Lifelong VISION, a Gravitation project funded by the Dutch Ministry of Education, Culture and Science (2024-2033), will develop new treatments against blindness.

Blindness is among the top 15 most disabling conditions and can manifest in many different ways. In young people, a hereditary retinal condition is the main cause, while in the elderly, age-related macular degeneration is a prominent reason. The Lifelong VISION program is developing a new generation of treatment strategies to prevent blindness: genetic therapies, treatments that target the disease pathways, and cell therapies. State of the art cell and animal models will be developed to test these new therapies in vitro and in vivo. The suitability of each patient group, and the optimal timing for therapeutic intervention is predicted using artificial intelligence, so that the right patient receives the right treatment at the right time. The innovative technologies and strategies developed for eye diseases within our project may serve as blueprints for other diseases and organs.

Ten research institutions participate in the Lifelong Vision project. The project is led by prof. dr. Caroline Klaver from Radboudumc and Erasmus MC; other institutions include Amsterdam UMC, University of Twente, Hubrecht Institute, Eindhoven University of Technology, University of Amsterdam, Utrecht University, Tilburg University, and Netherlands Institute for Neuroscience.

Would you like to know more about the different phases within the PhD trajectory? You can read more about this on this page.

Your main responsibility will be to develop, characterize and apply patient-based preclinical models. In doing so, you will work closely with researchers from Human genetics and clinicians from the Emma Children's Hospital and the department of Ophthalmology at Amsterdam UMC. Together, you will translate clinical questions into experiments and discuss what the results mean for understanding disease mechanisms and developing new treatments.

Your tasks will include:

• culturing patient-derived stem cells and developing and optimizing differentiation protocols for retinal cell and tissue models.
• characterizing new in vitro models at the molecular, cellular and functional levels and investigating the extent to which they reflect characteristics of the disease;
• contributing to the development and characterization of patient-based in vivo models and establishing relevant outcome measures for disease progression and treatment;
• applying the models to investigate cell therapy, including combining stem cell-derived cells with biomaterials and performing and evaluating preclinical transplantations;
• integrating experimental findings with genetic and clinical patient data, in collaboration with researchers and clinicians;
• presenting your results within Lifelong VISION, Emma CPM and at scientific meetings, and incorporating them into scientific publications and a PhD thesis.