Gijs Kooij

About

Gijs Kooij is a PI (associate professor) at the Department of Molecular Cell Biology & Immunology as well as the MS center Amsterdam. His main research focus is to understand the natural process to resolve neuro-inflammation in order to provide new perspectives on the pathogenesis of chronic (unresolved) neuro-inflammatory diseases like multiple sclerosis (MS) and to reveal new treatment opportunities. He recently discovered endogenous lipid mediator circuits in the central nervous system (CNS) and revealed the absence of protective lipid mediators in various disease stages of MS. These findings in combination with personal Vidi (NWO) and Fellowship (Dutch MS society) grants have enabled him to establish his own research group on inflammation-resolution mechanisms in health and disease.

Research Line

(Re)solving MS: Understand and exploit endogenous protection mechanisms.

Inflammation is a host-protective response when properly orchestrated. Beside immune checkpoints, the inflammatory cascade boasts an additional checkpoint, driven by chemical lipid mediators that induce resolution of inflammation. These novel autacoids, called specialized pro-resolving lipid mediators (SPMs), not only inhibit the inflammatory response, they also actively terminate it, leading to the restoration of tissue homeostasis. Novel sensitive detection methods (i.e. lipidomics) have set the stage to identify and decode these SPMs, which opens new perspectives on the pathogenesis of chronic (unresolved) inflammatory diseases like multiple sclerosis (MS).

By using a state-of-the-art lipidomics and mass-spectrometry imaging approach in combination with primary cell cultures, ex vivo brain slice cultures, in vivo neuro-inflammation models and human post-mortem tissues, we will elucidate in the coming years how altered inflammation-resolving mechanisms underlie MS pathogenesis by investigating both fundamental (Vidi) and clinical (fellowship) aspects. His ultimate goal is to provide novel diagnostic, prognostic and therapeutic opportunities for MS and other chronic (neuro-)inflammatory diseases based on resolution pharmacology (Figure 1).

**Figure. Decision paths during neuro-inflammation: chronicity or resolution?**
An effectively mounted inflammatory response will also trigger the activation of protective resolution pathways intended to safely terminate the inflammatory cascade and promote healing (1). Failed resolution can extend in time the actions of pro-inflammatory mechanisms resulting in prolonged (chronic) inflammation (2). I here propose that activation of endogenous circuits of resolution through novel resolution-based therapeutics (SPMs) can restore tissue structure and function to return to homeostasis (3).

Key publications

Broos JY, van der Burgt RTM, Konings J, Rijnsburger M, Werz O, de Vries HE, Giera M, Kooij G. Arachidonic acid-derived lipid mediators in multiple sclerosis pathogenesis: fueling or dampening disease progression? J Neuroinflamm 2024; 21(1):21. PMID: 38233951.
Broos JY, Loonstra FC, de Ruiter LRJ, Gouda M, Fung WH, Schoonheim MM, Heijink M, Strijbis EMM, Teunissen C, Killestein J, de Vries HE, Giera M, Uitdehaag BMJ, Kooij G. Association of arachidonic acid-derived lipid mediators with disease severity in patients with relapsing and progressive multiple sclerosis. Neurology 2023; 101(5):e533-e545. PMID: 37290971.
Derada Troletti C, Enzmann G, Chiurchiù V, Kamermans A, Tietz SM, Norris PC, Jahromi NH, Leuti A, van der Pol SMA, Schouten M, Serhan CN, de Vries HE, Engelhardt B, Kooij G. Pro-resolving lipid mediator lipoxin A4 attenuates neuro-inflammation by modulating T cell responses and modifies the spinal cord lipidome. Cell Rep 2021; 35(9):109201. PMID: 34077725.
Kooij G, Troletti CD, Leuti A, Norris PC, Riley I, Albanese M, Ruggieri S, Libreros S, van der Pol SMA, van Het Hof B, Schell Y, Guerrera G, Buttari F, Mercuri NB, Centonze D, Gasperini C, Battistini L, de Vries HE, Serhan CN, Chiurchiù V. Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction. Haematologica. 2020 Aug;105(8):2056-2070. PMID: 31780628.
Hansen CE, Konings J, Toth G, Chornyi S, Karsten M, van Het Hof B, van der Pol SMA, Beekhuis-Hoekstra SD, Kok N, Fung WK, Dijksman NS, Baron W, Witte ME, Lanekoff I, de Vries HE, Kooij G. Spatial mapping of the AA-PGE2-EP axis in multiple sclerosis lesions. Acta Neuropathol. 2025 Apr 29;149(1):39. PMID: 40299057.

Group members

Gema Muñoz González, MSc

PhD student
My research investigates early changes within the normal-appearing white matter of the Multiple Sclerosis brain. Specifically, we study subtle alterations in myelin lipids that may compromise myelin structure and lead to functional deficits. By integrating LC-MS/MS lipidomics, biochemical assays, and advanced microscopy techniques, we aim to understand the molecular triggers and consequences of these early myelin changes. Furthermore, we are currently establishing a human post-mortem organotypic slice culture model for investigating Multiple Sclerosis disease mechanisms and screening potential therapeutic interventions.