Challenge Workshop
June 18-22, 2026
Director: Steven Goldman
University of Rochester Medical Center, USA & University of Copenhagen, Denmark
Faculty:
Lorenz Studer, Memorial Sloan-Kettering, New York, USA
Giovanna Mallucci, Altos Labs, Cambridge, UK
Paul Tesar, Case Western University School of Medicine, Cleveland, USA
Maiken Nedergaard, University of Copenhagen, Denmark
Viviane Tabar, Memorial Sloan-Kettering, New York, USA
Robin Franklin, Altos Labs, Cambridge, UK
Steven Goldman, University of Rochester Medical Center, USA & University of Copenhagen, Denmark
Cellular rejuvenation is emerging as a new field within the broader topic of CNS repair. How can we overcome blocks to cellular differentiation? Can we reverse cell senescence? Can we do so in a controlled manner without triggering neoplasia? How might this process and its endpoints differ between neurons and glial cells? What are the most promising epigenetic and transcriptional targets and treatment strategies for safely reanimating quiescent stem and progenitor cells? What are the potential disease targets for such approaches? How might therapeutic transgenes and transcriptional modulators be best delivered to the brain and to the desired cellular targets? To discuss these and related issues, this workshop will bring together experts in this evolving field, each with distinct expertise and perspectives. Our goal will be to synthesise an actionable framework for this rapidly advancing corner of regenerative neurology.
Robin Franklin
Rejuvenating ageing oligodendrocyte progenitor cells
The two principal properties of adult stem cells are their ability to divide and to differentiate into the cell types of the tissue in which they reside. Both these properties become less efficient with increasing age, with deleterious consequences for tissue maintenance and regeneration – loss of which are well-recognised hallmarks of ageing. In our laboratory, we have studied this feature of adult stem biology, and how it might be reversed or rejuvenated, using the oligodendrocyte progenitor cell (OPC – also called the glial progenitor cell) as a model system.
With age, adult OPCs lose their ability to divide and differentiate efficiently. This loss of function leads to an increasing failure of adaptive myelination (a mechanism of learning) and remyelination (the regenerative response to oligodendrocyte loss in disease) and is in part due to changes in the mechanical properties of the ageing brain. However, youthful function can be restored in ageing OPCs by a number of interventions. This presentation will review these and discuss the broader implications for the biology of ageing and how they might be harnessed therapeutically.
Giovanna Mallucci
To functionally rejuvenate neurons in vivo
Several approaches can ‘rejuvenate’ aged and diseased neurons. We use non-Yamanaka approaches to functionally rejuvenate neurons in vivo. During the lectures, I will discuss stress response modulation and resilience mechanisms that restore impaired synaptic, mitochondrial and proteostatic function, leading to improved cognition and survival in neurodegenerative disease. Further attention will be devoted to translational implications for human treatment and to presenting early human experimental studies.
Lorenz Studer
Capturing neuronal age and rejuvenation in human PSC-based models
The human brain ages very slowly, and our ability to replicate this process in the laboratory has long lagged behind. Human pluripotent stem cell (hPSC)-derived neurons offer a unique window into the biology of neuronal aging: they are born young irrespective of donor history, yet can be experimentally guided towards aged-like states.
Our lab has pursued a convergent strategy: developing complementary tools to induce aging in hPSC neurons, establishing transcriptional frameworks to score the outcome, and exploring whether the process can be reversed. These efforts reveal aging not as a passive deterioration, but as an active, regulated state subject to molecular control.
Parallel efforts in the lab have focused on the mechanism of neuronal maturation and have identified an epigenetic barrier that enforces the protracted timeline over which human neurons mature. Manipulating this barrier may enable not only the more rapid adoption of adult-like neuronal maturation states but also offer an unexpected path towards cellular rejuvenation by restoring barrier factors within the neuronal lineage.
Our broader ambition is bidirectional: using age induction to model late-onset diseases such as Parkinson’s and Alzheimer’s disease, while exploring the possibility of age reversal as a strategy to enhance neuronal resilience to age and disease.
Viviane Tabar
Interplay among α-synucleinopathy, neuroinflammation, and dopamine neuron grafts in Parkinson’s disease
Human pluripotent stem cell–derived dopaminergic progenitor grafts have entered multiple Phase I studies, an ongoing Phase III program, and early autologous iPSC applications. There is growing interest in how the microenvironment affects the function of dopamine neuron grafts. To examine how a chronically diseased neuroinflammatory milieu shapes graft function, we used the 3K synucleinopathy mouse model (hSNCA (C57BL/6-Tg(Thy1-SNCA*E35K*E46K*E61K)), which exhibits progressive complex motor abnormalities, including tremor. We will discuss the impact of intrastriatal grafts on complex motor functions and the contribution of innate immune cells (microglia) to graft function. Our studies highlight the bidirectional crosstalk among α-synucleinopathy, neuroinflammation, and hES DA grafts, and suggest that rational modulation of the host immune microenvironment will be essential to maximize the durability and magnitude of benefit from dopaminergic cell replacement therapies in Parkinson’s disease
Paul Tesar
Glia and the regenerating CNS
Our laboratory investigates how glial cells acquire, maintain, and lose functional states in the developing, diseased, and regenerating central nervous system. We focus particularly on oligodendrocytes, oligodendrocyte progenitor cells, and astrocytes, using human stem cell models, genetic systems, and phenotypic discovery platforms to identify mechanisms that control glial maturation, dysfunction, and repair. Although our work is rooted in myelin disorders, including multiple sclerosis, leukodystrophies, and neurodegenerative disease, many of the same questions intersect with brain aging: why progenitor and support cells lose regenerative competence, how disease-associated glial states become locked in, and whether these states can be therapeutically redirected. Our goal is to define molecular pathways that restore glial function and resilience, opening new strategies for regenerative and disease-modifying therapies in the human brain.