Position | PhD-Student |
Research fields |
Former Education: BSc. in Biotechnology by the University of Brasília, Brazil (2017), MSc. in Molecular Medicine and Innovative Therapeutics (previously named Medical and Pharmaceutical Drug Innovation) cum laude by the University of Groningen (2019), the Netherlands.
Research Groups:
Department of Biomedical Sciences of Cells & Systems | Molecular Neurobiology (Eggen group)
&
Faculty of Science and Engineering | Groningen Research Institute of Pharmacy | Department of Molecular Pharmacology
Promotors: Bart Eggen & Erik Boddeke
Co-promotors: Amalia Dolga & Susanne Kooistra
Project: Microglia immune memory in multiple sclerosis.
Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system (CNS), and the most common non-traumatic neurological cause of disability in young adults. Current therapies reduce the frequency of relapses but have limited efficacy in preventing disease progression. Peripheral inflammation and infections can affect the CNS and influence the development of neurological diseases. Contrary to the classical view that immunological memory is restricted to the adaptive immune system, innate immune cells, such as microglia (the CNS-parenchyma macrophages), can also display an epigenetically-mediated innate immune memory. Microglia are implicated in several neuroinflammatory diseases, they sense microenvironmental cues and adapt with diverse activation states, and microglia epigenetics is key for their plasticity. Studies from our group and others show that repeated stimulation can induce long-lasting epigenetic changes in microglia and alter their subsequent response. Notably, repeated peripheral challenges with bacterial lipopolysaccharide (LPS) induce changes in microglia response and influence the development of neuropathology months later in stroke and Alzheimer’s disease (AD) models. However, how these epigenetic mechanisms orchestrate microglia immune memory, and whether this immune memory is implicated in MS is unknown. In my project I aim to investigate the mechanisms underlying microglia immune memory, using in vitro models, such as human induced pluripotent stem cells (hiPSC)-derived microglia, combined with state-of-the-art epigenomics and transcriptomics techniques, and real-time cell analysis instruments. Furthermore, I aim to assess the influence of microglia immune memory in MS mouse models, and to characterize the epigenetics of human microglia from MS patients. This study will give mechanistic insights into how epigenetics orchestrates immune memory and microglia function and its impact on neurodegeneration, neuroinflammation, and de/remyelination, aiding to identify novel intervention targets for the treatment of MS. Furthermore, the knowledge generated in this project will indicate factors that potentially drive other neurodegenerative diseases, such as AD, and neuropsychiatric disorders, such as schizophrenia and autism, in which microglia immune memory is also implicated.
Funding: Graduate School of Medical Sciences.
RUG: https://www.rug.nl/staff/t.medeiros.furquim.mendonca/research
Linkedin: https://www.linkedin.com/in/tiago-medeiros-furquim-mendonca/
Researchgate: https://www.researchgate.net/profile/Tiago_Medeiros_Furquim_Mendonca
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