MxW Connect - London 2026

Dr Madeline Lancaster is a Group Leader in the Cell Biology Division of the Medical Research Council (MRC) Laboratory of Molecular Biology, part of the Cambridge Biomedical Campus in Cambridge, UK. Madeline studied biochemistry at Occidental College, Los Angeles, USA, before completing a PhD in 2010 in biomedical sciences at the University of California, San Diego, USA. She then joined the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA) in Vienna, Austria as a postdoctoral researcher in the Knoblich lab where she developed the first brain organoids, or cerebral organoids, before joining the LMB in 2015.

Professor Selina Wray is a Professor of Molecular Neuroscience in the Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology. Her work focussing on understanding the molecular mechanisms of Alzheimer’s disease and other forms of dementia using patient-derived stem cell models. Selina received her degree in Biochemistry and Biological Chemistry from the University of Nottingham in 2004 and was awarded her PhD in 2008 from Kings College London. She joined UCL Queen Square Institute of Neurology in 2009 as a postdoc with Professor John Hardy, supported by Alzheimer’s Research UK Junior and Senior fellowships, before establishing her own group.

Understanding clinical heterogeneity in Alzheimer’s disease and related dementias using personalised stem cell models

iPSC-based models provide a powerful platform to study the human biology of Alzheimer’s disease and related dementias. In this talk, I will present our work using iPSC systems to model familial Alzheimer’s disease (fAD), focusing on mutation-specific effects of APP and PSEN1 on Aβ generation and processing, and Familial British Dementia (FBD), focusing on cell type specific contributions to amyloid production. I will discuss how advanced in vitro systems can be used to capture and dissect the cellular, clinical and pathological heterogeneity that underpins these disorders. A particular focus will be placed on approaches to benchmark model fidelity against patient-derived tissues and biofluids, enabling more accurate representation of disease mechanisms and improving translational relevance. Together, these strategies aim to move preclinical modelling towards more predictive, human-relevant systems that can better inform therapeutic development.

I studied Medicine at the University of Birmingham (1991-97) and continued my general medical training in Oxford. I then spent three years working on the genetic linkage and association of neurological disorders at the Wellcome Trust Centre for Human Genetics. After obtaining my DPhil in 2003, I completed my training in Clinical Neurology at Oxford. I joined the Department of Physiology, Anatomy and Genetics in 2007 after being awarded an MRC Clinician Scientist Fellowship to establish my own research group. I then led IMI StemBANCC - an large public-private partnerhsip funded by the EU to establish iPSC resources for academia and industry across europe.

I now lead IMI IM2PACT which is an amibitious research programme to investigate disease mechanism involving the brain neurovascular unit and find transport mechanisms to get therapeutics into the brain.

My research group aims to develop resources and tools to improve drug discovery by leveraging human data and human iPSC brain models. We work on pain/migraine, Alzheimer's disease and autism/epilepsy.

I am also active clinically and work as a Consultant Neurologist at the John Radcliffe Hospital with an interest in Headache Disorders. I am Director of the Oxford Headache Centre and developed the Oxford Community Headache Service.

Zoltán Molnár is Professor of Developmental Neuroscience at the University of Oxford. He is known for key contributions to our understanding of how the birth of cortical neurons is regulated, how they migrate, differentiate, generate axons and assemble into circuits, and how those circuits change over time, partly as a result of activity passing through them.

Molnár earned his M.D. at the Albert Szent-Györgyi Medical University, Szeged, Hungary and D.Phil. at the University of Oxford, UK. He also investigated thalamocortical development working at the Institut de Biologie Cellulaire et de Morphologie, Université de Lausanne, Switzerland, and learned optical recording techniques to understand early functional thalamocortical interactions at Kyoto Prefectural School of Medicine, Japan.

He was appointed to a University Lecturer position at the Department of Human Anatomy and Genetics at Oxford associated with an Official Fellowship and Tutorship at St John's College from 2000. He was awarded the title Professor of Developmental Neuroscience in 2007. Molnar has been Elected Member of Academia Europaea (Physiology and Neuroscience); European Neonatal Brain Club; Fellow of the Anatomical Society, Awarded New Fellow of the Year Award for 2018.

I studied Pharmacology (B.Sc. Hons) at the University of Edinburgh between 2001 – 2005. In 2005, I joined the Department of Neuroscience, University of Dundee, to undertake a BBSRC-Case PhD studentship. Here, using patch-clamp electrophysiology techniques, I examined the structure-function of pentameric ligand-gated ion channels. My time in Dundee included a short post-doctoral position (JBC, 2008 and JBC, 2011).

I joined the University of Edinburgh at the start of 2011 and undertook a postdoctoral position to examine the functional capabilities and developmental properties of pluripotent stem cell-derived cortical neurons (J.Neurosci, 2014; J.Physiol, 2014 and PLoS One, 2014). In this time I became interested in using this technology in order to model disease, specifically amyotrophic lateral sclerosis and frontotemporal dementia, and was awarded a Royal Society of Edinburgh Fellowship (2015) in order to investigate synaptic impairments in ALS-FTD (Nature Neuroscience, 2016; Nature Communications, 2018; J.Pathology, 2020; Molecular Neurodegeneration, 2021). Furthermore, noting the increasing appreciation of the roles of non-neuronal cell types in healthy neuronal health and disease, I have also explored the functional properties of oligodendrocytes-derived from ALS patients (Stem Cells, 2016) and also began to examine the heavily underexplored area of oligodendrocyte physiology (Glia, 2019; Journal of Neuroscience, 2021).

In March 2020, I arrived at SITraN as a principle investigator to lead work on neurophysiological perturbations and their mechanistic bases in ALS-FTD.

I graduated from medical school at the Georg-August-University Göttingen in Germany with both a medical degree and a research MD (summa cum laude and prize for the best thesis of the year). My MD project with Paul Lingor investigated the role of the autophagic protein ULK1 in axonal degeneration and regeneration. I subsequently completed an MSc in Neuroscience and a DPhil in Clinical Neurosciences at the Oxford Motor Neuron Disease Centre with Kevin Talbot and Martin Turner, focusing on the role of microglia in ALS. During my DPhil I was Clarendon Scholar and held additional scholarships from St John’s College, the MRC, and NIHR. After three years as a Postdoctoral Researcher in the Talbot Lab, I am now an independent Research Fellow, funded by an MNDA Lady Edith Wolfson Fellowship. I am also Junior Research Fellow at Kellogg College, having previously served as Fulford Junior Research Fellow at Somerville College.

Thomas received his Integrated Master’s degree in Neuroscience from King’s College London, United Kingdom in 2023, where he completed a project investigating lipid dysregulation during ageing in human neural stem cells in the laboratory of Professor Sandrine Thuret. After this, he worked as a Research Assistant in the group of Marc-David Ruepp (King’s College London) exploring the cellular cold-shock response and it’s potential in the treatment of amyotrophic lateral sclerosis.

Thomas joined the Pluchino lab in January 2025 as a PhD student funded by the Doctoral Training Program in Medical Research (School of Clinical Medicine, University of Cambridge). Utilising brain organoids, he will be investigating the interplay between senescent neural stem cells present in MS and healthy brain cells, supervised by Alex Nicaise.

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New Approach Methodologies for MS Research

Progressive multiple sclerosis (pMS) remains a major unmet clinical need, with smouldering neuroinflammation and neurodegeneration driven by complex CNS-intrinsic mechanisms that traditional animal models fail to recapitulate adequately. New approach methodologies (NAMs) leveraging human patient-derived systems offer a transformative opportunity to study these processes with unprecedented fidelity. Our laboratory has developed a progressive NAM framework, moving from patient-derived 2D induced neural stem cell (iNSC) cultures — generated via direct reprogramming to preserve disease-relevant epigenetic memory — towards sophisticated 3D patient hybridoid models. These novel human hybridoids are built on developmentally mature air-liquid interface cortical organoids (ALICOs) transplanted with control or patient-derived iNSCs, enabling the study of neuroimmune interactions within a structured, physiologically relevant architecture.

To comprehensively phenotype and interrogate these models, we apply an integrated multi-module analytical strategy encompassing spatial transcriptomics to resolve disease-associated cellular states in their tissue context, multielectrode array (MEA) recordings to capture functional network dynamics, and RABIDseq to map intercellular communication at single-cell resolution. Together, this NAM pipeline — spanning patient-specific 2D cultures through to functionally and molecularly profiled 3D hybridoids — represents a powerful new platform for dissecting pMS pathogenesis and identifying novel therapeutic targets.