The Mews Lab defines how metabolic signals and experience converge to drive epigenetic plasticity in the brain, shaping cognition, memory, and behavior across the lifespan.

Mechanisms of Brain Plasticity
We study how metabolism and epigenetic regulation converge to control brain function and behavior.
With a focus on neuroepigenetics and substance use disorders, our work seeks to define the molecular pathways through which metabolic
states influence chromatin dynamics—the regulatory processes that govern gene expression in neurons. By elucidating these mechanisms,
we aim to understand how metabolic–epigenetic coupling shapes neural plasticity, cognition, and vulnerability to disease.

Addiction & Epigenetic Priming in Relapse
Why does relapse occur even after prolonged abstinence? We explore how drugs such as cocaine and alcohol induce profound,
long-lasting changes in the brain's genetic programming that persist well beyond drug exposure.
By defining how these substances remodel chromatin—the molecular architecture that governs how DNA is packaged and read—we uncover
epigenetic mechanisms that drive addiction and vulnerability to relapse. Our goal is to identify therapeutic targets that
can reverse these maladaptive epigenetic states and reduce relapse risk.

Metabolic Control of Memory
How does metabolism shape the formation and persistence of memory? Our work establishes a direct link between
systemic metabolic state and gene regulation in the hippocampus, a brain region essential for learning and memory.
We have shown that the metabolic enzyme ACSS2 is recruited to the neuronal nucleus, where it converts acetate into acetyl-CoA to fuel
histone acetylation required for spatial memory formation. Building on this discovery, we investigate how fluctuations in
metabolic state influence chromatin dynamics. Our long-term goal is to identify strategies to modulate maladaptive memories,
including those relevant to trauma-related disorders, and to sustain cognitive function over time.

Aging & Neurodegeneration
How does aging compromise the epigenetic stability required for long-term memory and brain function?
Building on our work in metabolic–epigenetic coupling, we investigate how age-related metabolic dysfunction disrupts the
epigenetic mechanisms that maintain neuronal identity and cognitive function. We focus on how declining availability of key metabolic substrates,
such as acetyl-CoA, leads to transcriptional dysregulation and impaired chromatin regulation in aging neurons. Our goal is to define how
metabolic failure progressively erodes epigenetic maintenance of memory and to identify strategies that preserve cognitive resilience across the lifespan.

Toolkit
We employ a multi-scale approach to interrogate brain function, integrating cutting-edge molecular, cellular, and behavioral techniques.
By combining advanced genomic, epigenomic, proteomic, and in vivo behavioral approaches, we dissect how metabolic signaling regulates chromatin and neural function.

Join the Lab
We welcome inquiries from motivated scientists at all career stages.
The Mews Lab is currently recruiting outstanding Postdoctoral Fellows and Graduate Students,
and regularly hosts undergraduate researchers and interns interested in rigorous, discovery-driven neuroscience.

https://www.philippmewslab.com