Understanding the complex interplay between the immune system and neurological health, particularly exploring the roles of innate immune cells and metabolic pathways in neurodegenerative diseases, neuropsychiatric disorders, and the aging process, aims to uncover novel therapeutic avenues for improving patient outcomes.

The Neuroimmunomics group led by Dr John Lee at SBMS represents a pivotal initiative in advancing our understanding of the complex interplay between the immune system and neurological disorders. This research endeavour is crucial in the context of addressing pressing health challenges such as motor neuron disease (MND), Huntington's Disease (HD), Parkinson's Disease (PD), and neuropsychiatric disorders.


Our research group is at the forefront of investigating the intricate roles played by innate immune cells - including neutrophils, macrophages, microglia, and astrocytes - in these neurological conditions. Emerging evidence suggests that dysregulation of immune responses within the central nervous system contributes significantly to disease progression and pathology.

Previous studies have highlighted the importance of understanding the metabolic capacity of these innate immune cells and its implications for neuroinflammation and neurodegeneration. Our research focuses on elucidating the underlying mechanisms of immunometabolism in neuroinflammatory processes, with the ultimate goal of identifying novel therapeutic targets.

Furthermore, our investigations extend beyond traditional neuroimmunology paradigms to explore the intricate connections between the immune system and other physiological processes, such as the stress response and aging. By uncovering the links between immune dysregulation and neuropsychiatric disorders, as well as age-related neurological changes, our research provides critical insights into potential therapeutic interventions.

Through collaborative efforts with clinicians, researchers, and industry partners, our research group aims to advance the field of neuroimmunology and immunometabolism, ultimately leading to the development of innovative treatments and personalized approaches for patients affected by neurological disorders.

Our research areas

Neuroimmunology in neurodegenerative diseases

We explore the involvement of innate immune cells in the pathogenesis of MND, HD, and PD to identify potential therapeutic targets. By elucidating the mechanisms underlying neuroinflammation, we aim to develop interventions that halt or slow disease progression.

Immunometabolism in neuroinflammation

Our group investigates the metabolic capacity of innate immune cells within the central nervous system, including neutrophils, macrophages, microglia, and astrocytes. By understanding how alterations in cellular metabolism impact immune function, we aim to uncover new strategies for modulating neuroinflammatory responses.

Immune system – Stress response crosstalk

We explore the intricate relationship between the immune system and the stress response, particularly its implications in neuropsychiatric disorders. By unravelling the molecular mechanisms underlying this crosstalk, we aim to identify new therapeutic targets for conditions such as depression, anxiety, and post-traumatic stress disorder (PTSD).

Immunosenescence and Neurological Aging

Our group investigates the link between the immune system and aging within the context of neurological health. By studying age-related changes in immune function and their impact on brain health, we aim to develop interventions that promote healthy aging and mitigate age-related neurological disorders.


We have 4 main objectives. These are to:

  1. Characterise the activation states and functional roles of innate immune cells in neurodegenerative diseases, aiming to identify potential therapeutic targets
  2. Conduct detailed metabolic profiling of neutrophils, macrophages, microglia, and astrocytes to elucidate the impact of altered metabolism on immune function and neuroinflammatory responses.
  3. Investigate the molecular mechanisms underlying the crosstalk between the immune system and the stress response, with a focus on identifying biomarkers and therapeutic interventions for neuropsychiatric disorders.
  4. Examine age-related changes in immune function and their contribution to neurological aging and age-related neurodegenerative diseases, with the aim of developing interventions to promote healthy aging and mitigate age-related neurological disorders.

Within our research group focused on neuroimmunology and immunometabolism, our primary objective is the identification of new therapeutic targets. Through molecular profiling, functional assays, in vivo models, and analysis of clinical samples, we aim to uncover promising candidates for targeted interventions in neurological disorders, neuropsychiatric conditions, and age-related neurodegeneration.

  • Cell culture: Primary culture of neurons, astrocytes, microglia, neutrophils, and macrophages from mouse and human
  • Animal models: MND, HD, PD, and Neuropsychiatric disorders
  • Efficacy testing: Pharmacokinetics, and pharmacodynamics
  • Motor and cognitive behavioural analysis: Grip strength, rotarod, balance beam, wire hang, open field, activity monitor, APA, Y – maze, and elevated plus maze
  • Immunohistochemistry and Immunofluorescence
  • Flow Cytometry
  • Metabolic Assays: Biolog, Seahorse Extracellular Flux Analyser, Metabolic flux analysis using stable isotope tracers, enzyme activity assays, GTT, ITT, and glucagon tolerance test
  • Gene Expression Analysis: Quantitative real-time PCR, and RNA sequencing
  • Protein Analysis: Western blotting, ELISA, and multiplex cytometry beads array
  • Spatial Techniques: Spatial proteomics, spatial metabolomics (Neurotransmitter), and RNAScope
  • Mass Spectrometry Techniques: Proteomics, metabolomics, and lipidomics

Selected research articles

  • Chen HC, Spiers JG, Lerskiatiphanich T, Parker SE, Lavidis NA, Fung JN, Woodruff TM, Lee JD. (2024). Complement C5a receptor signaling alters stress responsiveness and modulates microglia following chronic stress exposureBiological Psychiatry: Global Open Science. doi: 10.1016/j.bpsgos.2024.100306

  • McDonald TS, Kumar V, Fung JN, Woodruff TM, Lee JD. (2021). Glucose clearance and uptake is increased in the SOD1G93A mouse model of amyotrophic lateral sclerosis through an insulin‐independent mechanismThe FASEB Journal, 35 (7) e21707, e21707. doi: 10.1096/fj.202002450r
  • Lee JD, Heshmat S, Heggie S, Thorpe KA, McCombe PA, Henderson RD. (2021). Clinical and electrophysiological examination of pinch strength in patients with amyotrophic lateral sclerosis. Muscle and Nerve, 63 (1) mus.27111, 108-113. doi: 10.1002/mus.27111
  • Lee JD, McDonald TS, Fung JN, Woodruff TM. (2020). Absence of Receptor for Advanced Glycation End Product (RAGE) Reduces Inflammation and Extends Survival in the hSOD1 Mouse Model of Amyotrophic Lateral Sclerosis. Molecular Neurobiology, 57 (10), 4143-4155. doi: 10.1007/s12035-020-02019-9
  • Deora V, Lee JD, Albornoz EA, McAlary L, Jagaraj CJ, Robertson AAB, Atkin JD, Cooper MA, Schroder K, Yerbury JJ, Gordon R, Woodruff TM. (2020). The microglial NLRP3 inflammasome is activated by amyotrophic lateral sclerosis proteins. Glia, 68 (2) glia.23728, 407-421. doi: 10.1002/glia.23728
  • Lee JD, Levin SC, Willis EF, Li R, Woodruff TM, Noakes PG. (2018). Complement components are upregulated and correlate with disease progression in the TDP-43 mouse model of amyotrophic lateral sclerosis. Journal of Neuroinflammation, 15 (1) 171, 171. doi: 10.1186/s12974-018-1217-2
  • Lee JD, Kumar V, Fung JN, Ruitenberg MJ, Noakes PG, Woodruff TM. (2017). Pharmacological inhibition of complement C5a-C5a1 receptor signalling ameliorates disease pathology in the hSOD1G93A mouse model of amyotrophic lateral sclerosis. British Journal of Pharmacology, 173 (8), 689-699. doi: 10.1111/bph.13730
  • Spiers JG, Chen HC, Steyn FJ, Lavidis NA, Woodruff TM, Lee JD. (2017). Non-invasive assessment of altered activity following restraint in mice using an automated physiological monitoring system. Stress, 20 (1), 59-67. doi: 10.1080/10253890.2016.1276898
  • Woodruff TM, Lee JD, Noakes PG. (2014). Role for terminal complement activation in amyotrophic lateral sclerosis disease progression. Proceeding of the National Academy of Sciences of the United States of America, 111 (1), E3-E4. doi: 10.1073/pnas.1321248111
  • Lee JD, Kamaruzaman NA, Fung JN, Taylor SM, Turner BJ, Atkin JD, Woodruff TM, Noakes PG. (2013). Dysregulation of the complement cascade in the hSOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis. Journal of Neuroinflammation, 10 (1) 119, 119. doi: 10.1186/1742-2094-10-119

Selected reviews

  • McDonald TS, Lerskiatiphanich T, Woodruff TM, McCombe PA, Lee JD. (2022). Potential mechanisms to modify impaired glucose metabolism in neurodegenerative disorders. Journal of Cerebral Blood Flow and Metabolism, 43 (1), 26-43. doi: 10.1177/0271678x221135061
  • McDonald TS, McCombe PA, Woodruff, TM, Lee JD. (2020). The potential interplay between energy metabolism and innate complement activation in amyotrophic lateral sclerosis. The FASEB Journal, 34 (6) fj.201901781, 7225-7233. doi: 10.1096/fj.201901781
  • Parker SE, Hanton AM, Stefanou SN, Noakes PG, Woodruff TM, Lee JD. (2019). Revisiting the role of the innate immune complement system in ALS. Neurobiology of Disease, 127, 223-232. doi: 10.1016/j.nbd.2019.03.003

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