research
The brain is one of the most lipid-rich organs in the body, with lipids comprising nearly half of its dry weight. These molecules are far more than structural building blocks—they regulate cellular communication, energy metabolism, inflammation, and myelin formation. Despite their central importance, we still know remarkably little about how lipid metabolism shapes brain function and contributes to neurological disease.
Glial cells—including microglia, astrocytes, and oligodendrocytes—are the major producers, processors, and regulators of lipids in the central nervous system. Oligodendrocytes generate the vast lipid-rich membranes that form myelin, astrocytes synthesize and distribute lipids throughout the brain, and microglia dynamically remodel lipids in response to injury and disease. Together, these cells maintain the lipid environment required for healthy brain function.
The Prakash Lab studies how glial cells regulate brain lipid biology and how disruption of these processes contributes to neurodegeneration.
Our work is driven by a central question: How do changes in glial cell state alter lipid metabolism, and how do these changes drive brain disease?
To address this question, we investigate the biology of microglia, astrocytes, and oligodendrocytes across multiple neurological disorders. Our research has shown that lipid accumulation impairs microglial function in Alzheimer's disease (Immunity, 2025), that reactive astrocytes release toxic lipid species that damage neurons and oligodendrocytes, and that oligodendrocyte dysfunction and myelin pathology are key features of X-linked dystonia-parkinsonism (bioRxiv, 2025). Together, these discoveries suggest that disrupted lipid metabolism is a critical mechanism linking glial dysfunction to neurodegeneration.
Moving forward, we aim to understand how lipid metabolism regulates glial function across development, aging, and disease. We are particularly interested in how lipid pathways influence oligodendrocyte lineage cells, how astrocytes and microglia shape myelin biology, and why specific brain regions show selective vulnerability during neurodegeneration.
Our long-term goal is to establish the fundamental principles of glial lipid biology and leverage these discoveries to identify new therapeutic targets and strategies for neurological disease.
key questions
How does lipid metabolism regulate glial cell identity and function?
How do glial cells coordinate lipid homeostasis across the brain?
How does lipid dysregulation contribute to neurodegeneration?
Can restoring glial lipid balance promote repair and resilience?
tools & techniques
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cellular & molecular biology
We use primary glial cultures, co-culture systems, and molecular techniques to investigate the mechanisms that govern glial function.
Image: Amyloid-β (red) within mouse microglia (green).
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lipid biochemistry
We use biochemical, lipidomic, and spatial profiling approaches to investigate how lipid metabolism regulates glial biology and contributes to disease.
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mouse models
We use transgenic and conditional mouse models to determine how glial dysfunction influences physiology, behavior, and disease progression.
Image: A mouse on a CatWalk platform for gait analysis.
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human studies
We analyze postmortem human tissue and multi-omics datasets to determine how findings from experimental models translate to human disease.
Image: Myelin basic protein (green) in the human striatum.
support
We are incredibly grateful for the generous support of those who fund our work, including Alzheimer’s Association, Department of Pharmacological Sciences, and Renaissance School of Medicine at Stony Brook University.
To support the important work that we do, consider donating to our mission.