Research team
Expertise
I am a neuroimmunologist with over seven years of experience investigating how immune cells contribute to brain inflammation and degeneration. My research combines advanced flow cytometry, single-cell RNA sequencing and proteomic approaches to uncover immune mechanisms driving viral encephalitis and neurodegenerative diseases such as Alzheimer’s and motor neuron disease. I have developed methods to distinguish and analyze microglia and monocytes in the inflamed brain, revealing their distinct roles in neuroinflammation and identifying potential biomarkers and therapeutic targets for early disease detection and intervention.
Brain border immunity in Parkinson's disease.
Abstract
Parkinson's disease (PD) is the fastest growing neurological disorder and is projected to become the second leading cause of death worldwide by 2040. Accumulation and spreading of alpha-synuclein (aSyn) ultimately results in a loss of neurons in the brain stem inducing a devastating decline in motor and non-motor functions. Mounting clinical and experimental evidence supports two potential origins of aSyn pathology: a brain-first or body-first initiation. In the brain-first model, αSyn aggregation is thought to begin in the brain, spreading later to peripheral sites, while in the body-first model, pathology emerges in organs such as the gut and ascends via autonomic pathways to the brain. Brain borders surrounding the central nervous system (CNS) parenchyma are emerging as key sites in the neuroimmune regulation. These regions connect peripheral immune activity to CNS inflammation and act as immune hubs where cerebrospinal fluid and blood-derived molecules are monitored by border-associated macrophages (BAMs). In PD, BAMs are gaining attention as their depletion reduces aSyn-induced neuroinflammation. I hypothesize that BAMs are central regulators of disease progression in both forms of aSyn pathology. I propose that BAMs respond to peripheral and CNS-intrinsic αSyn in body-first and brain-first PD, respectively, thereby coordinating immune signalling between the brain and periphery. I suspect this promotes peripheral immune cell activation and recruitment, amplifying αSyn propagation and neuroinflammation. Secondly, I propose that circulating immune cells recruited to the CNS in PD can be identified in the blood of high-risk patients, where they may serve as biomarkers of early disease or as potential therapeutic targets to reduce disease progression. More specifically, this proposal aims to: 1.CHARACTERIZE BRAIN BORDER IMMUNE POPULATIONS IN PD MODELS: Using two mouse models, including aSyn fibril injections into the CNS or ENS, I will characterize BAM phenotypes and functions using spectral cytometry and single-cell RNA sequencing. These methods are well established in the host lab. 3.IDENTIFY PERIPHERAL IMMUNE SIGNATURES IN PD PATIENTS WITH PRIOR INFECTION: PBMCs are being collected at Antwerp University Hospital and will be analysed by spectral cytometry to identify populations capable of CNS migration and contributing to PD risk. These markers could serve as diagnostic tools or therapeutic targets to limit neuroinflammation. OUTCOMES: This project aims to reveal how brain border immunity drives PD progression. Specifically, it seeks to identify immune-modifying strategies that prevent BAM-mediated recruitment of pathogenic cells into the CNS, blood-based biomarkers for disease monitoring, and trafficking molecules that can be targeted to inhibit CNS infiltration. This research will significantly advance our understanding of PD with scientific, societal and economic implications. Moreover, as a senior postdoc, acquiring independent funding will represent a critical first step enabling me to establish research independence for my career development and the growth of my research group.Researcher(s)
- Promoter: Spiteri Alanna
Research team(s)
Project type(s)
- Research Project