Research team
Expertise
My research expertise centres on tissue-resident macrophages, immune cell trafficking, neuroimmune interactions, and peripheral contributions to neurodegeneration, particularly in Parkinson’s disease (PD) and Alzheimer’s disease (AD). I employ state-of-the-art in vivo models, single-cell technologies, and spatial proteomics to dissect immune mechanisms in brain disorders. Key research activities include, but are not limited to: -Tissue-resident macrophage function and phenotype, with focus on the gastrointestinal tract -Immune cell trafficking studies: Using animal models to track immune cell migration between the periphery and the brain. -Single-cell and spatial transcriptomics to map immune cell heterogeneity and interactions in neurodegenerative disease models and human tissue. -Proteomic and secretome analyses to identify immune-derived factors along the gut-brain axis -Neuroinflammation and metabolic crosstalk -Behavioural and neuropathological analyses: Evaluating cognitive and motor deficits, α-Syn aggregation, and Aβ pathology in mouse models
VIB-Breaking Barriers: Peripheral Immune Mechanisms in Early Parkinson's Disease (PRIME-PD).
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by alpha-synuclein (α- Syn) aggregation. Despite being the fastest-growing neurodegenerative condition in terms of patients affected, there are currently no disease-modifying treatments and diagnosis typically occurs after significant neurodegeneration has already taken place. Intervening in the prodromal phase remains the critical challenge, and gaining a deeper understanding of the underlying pathophysiology is essential. Compelling evidence suggests that α-Syn might aggregate early in the enteric nervous system, spreading to the brain via the vagus nerve and triggering immune cell migration into the brain, where they contribute to disease progression. This project aims to address three key questions: 1) How are peripheral immune cells recruited to the brain in early α-Syn pathology? 2) How do peripheral immune cells interact with brain-resident cells to modulate the spread of α-Syn and neurodegeneration? 3) How do immune profile changes in the blood of high-risk prodromal PD patients relate to disease progression? To answer these questions, I will investigate the entry of peripheral immune cells to the brain using cutting-edge proximity and enzymatic labelling strategies; determine the immune interactome underlying α-Syn pathology and spread by combining α-Syn aggregation assays with in- situ spatial sequencing; and characterize circulating immune cells in prodromal PD patients by employing a humanized engraftment model to link peripheral immune phenotypes to disease progression in patients. By integrating these innovative techniques, this research aims to uncover how peripheral immune cells contribute to the onset and progression of PD, identifying new biomarkers and therapeutic targets for early intervention. Modifying immune cells in the blood to modulate the brain's immune environment represents a major shift in treating PD as a multisystem neuroimmune disorder.Researcher(s)
- Promoter: De Schepper Sebastiaan
Research team(s)
Project type(s)
- Research Project
Understanding the Immune Response driving Peripheral Synucleinopathy in Parkinson's disease.
Abstract
Parkinson's disease (PD) is a rapidly growing neurological disorder that primarily affects movement, leading to symptoms like slowed movement and tremors, but it also impacts other tissues and organs, including the gut and bladder. The disease is marked by the abnormal clumping of a protein called alpha-synuclein (α-Syn). Scientists believe that these clumps may start forming in parts of the body, such as the gut, long before they appear in the brain, contributing to the progression of the disease. New research suggests that particular cells of the immune system, termed 'macrophages', might play a crucial role in how these α-Syn clumps spread from the body to the brain. These macrophages normally help keep the gut healthy, but may start malfunctioning, leading to the buildup and spread of α-Syn clumps. My project aims to uncover how these gut immune cells interact with α-Syn and how this interaction might drive the disease from the gut to the brain. By studying the proteins involved in this process and the role of the immune system, this research hopes to identify new ways to detect PD early and develop treatments that could prevent or slow down its progression. This research is crucial because it addresses a largely unexplored area of PD—how the disease may start outside the brain. Understanding this could open up new avenues for diagnosing and treating PD much earlier than currently possible, potentially improving the lives of those at risk.Researcher(s)
- Promoter: De Schepper Sebastiaan
- Co-promoter: Rademakers Rosa
Research team(s)
Project type(s)
- Research Project
Neuro-immunology of the gut–brain axis
Abstract
My research programme focuses on the immune mechanisms driving neurodegeneration, with a particular emphasis on tissue-resident macrophages, immune cell trafficking, and peripheral inflammatory signals in Parkinson's disease and Alzheimer's disease.Researcher(s)
- Promoter: De Schepper Sebastiaan
- Fellow: De Schepper Sebastiaan
Research team(s)
Project website
Project type(s)
- Research Project
Deciphering the gut-brain axis in Parkinson's disease: the role of muscularis macrophages in immune cell trafficking and α-synuclein pathology.
Abstract
Parkinson's disease (PD) is one of the fastest-growing neurodegenerative disorders. Alpha-synuclein (α-Syn) aggregation and propagation play a central role in PD pathology, yet the cellular mechanisms driving these processes remain unclear. Recent studies suggest that in 'body-first' PD, α-Syn pathology originates in peripheral tissues, particularly the enteric nervous system, before migrating to the brain via the vagus nerve. We hypothesize that muscularis macrophages, a subset of innate immune cells in the gut, modulate α-Syn pathology and its spreading to the brain. We will elucidate the signalling pathways and immune cells involved in α-Syn migration and immune responses along the gut-brain axis. We will apply cutting-edge in vivo labelling techniques to (i) map the immune interactions of muscularis macrophages and (ii) identify the secreted signals driving immune cell recruitment to the brain. Our findings will not only advance our understanding of the peripheral immune mechanisms governing PD but also provide novel insights for the development of therapeutic strategies targeting early disease intervention.Researcher(s)
- Promoter: De Schepper Sebastiaan
Research team(s)
Project type(s)
- Research Project