Hofer Lab
Targeting immune signalling in neuroinflammation and early brain health
Our research investigates how immune signalling shapes both brain inflammation and development. Chronic neuroinflammation underpins many debilitating neurological disorders, including Aicardi-Goutières syndrome, yet the immune pathways that drive and sustain this inflammation are still not fully understood. In parallel, maternal immune activation has emerged as a critical risk factor for neurodevelopmental disorders such as autism, highlighting the need to unravel how early immune cues disrupt brain development.
The Hofer Lab focuses on interferons—potent cytokines that not only protect against viral infections but also shape inflammatory processes in the brain. Using advanced mouse models and cell-based systems, we investigate how interferon signalling is regulated, and how its dysregulation contributes to neuropathology. Our goal is to uncover key cellular and molecular drivers that could be targeted to prevent or reverse immune-mediated damage in the central nervous system.
We collaborate with leading biopharmaceutical companies that are at the forefront of developing innovative immunological therapies, including those specialising in antisense technology, neuroinflammatory diseases, and innate immune modulation. We also partner with patient advocacy organisations such as the Aicardi-Goutières Syndrome Advocacy Association (AGSAA) to help drive research outcomes that truly matter to patients and families.
By bridging basic science and therapeutic discovery, our research has the potential to inform new strategies for treating neuroinflammatory and neurodegenerative diseases.
Aicardi-Goutières syndrome (AGS) is a rare and severe genetic disorder that causes debilitating brain inflammation, leading to developmental delays and early childhood death. The disease is driven by excessive immune signalling in the brain, particularly interferon-alpha. Our research has identified brain blood vessels as a key target of this immune overreaction, offering new insights into AGS. This discovery shifts the focus from just controlling inflammation to protecting the brain's microvasculature, opening doors to more effective treatments that could change the prognosis for children with AGS.
Neurodevelopmental disorders (NDDs) such as autism and ADHD affect nearly 1 in 10 children. Maternal immune activation—triggered by infection, obesity, or stress during pregnancy—is a key risk factor, disrupting foetal brain development through inflammatory and epigenetic mechanisms. Using advanced mouse models, we investigate how maternal immune signals alter neural development and identify the critical windows of vulnerability. In collaboration with clinicians at Westmead Children’s Hospital, we also assess whether anti-inflammatory interventions can prevent or reduce NDD risk—bridging experimental insights with potential early-life therapeutic strategies.
Cytokine signalling plays a pivotal role in neuroinflammation, influencing both the immune response and neuronal function in the brain. In diseases like multiple sclerosis, Alzheimer’s, and other neurodegenerative conditions, dysregulated cytokine activity exacerbates inflammation, leading to neuronal damage. Key cytokines, such as interferons, interleukins, and tumour necrosis factors, can either protect or harm the brain depending on their regulation. Our research focuses on understanding how these cytokines contribute to neuroinflammatory processes and identifying therapeutic targets to modulate their effects, offering potential treatments for a range of neurological diseases driven by chronic inflammation.
Associate Professor Markus Hofer and Professor Greg Sutherland
Brain Bank Connect is an initiative aimed at establishing a global network of brain banks to advance research and treatment for rare neurological disorders in children. Recognising the critical role of brain tissue in understanding these conditions, the project seeks to address challenges such as fragmentation, lack of global standards, and limited focus on paediatric diseases in existing brain banking practices. By uniting tissue banks, clinical centres, patient advocacy groups, researchers, clinicians, and other stakeholders, Brain Bank Connect aims to enhance collaboration and accelerate progress in the study and treatment of rare neurological diseases affecting children
Hofer Lab is led by Associate Professor Markus Hofer. For more information, please contact: Markus Hofer at markus.hofer@sydney.edu.au and visit our webpage at www.hoferlab.com.
