Neural Stem Cells at the Interface of Development and Immunity
The human brain is built by a small, transient population of cells with extraordinary power: neural stem cells (NSCs). In our lab, we want to understand how these cells make decisions — and what goes wrong when they don't.
OUR VISION
From a single population of neural stem cells emerges the staggering diversity of the human brain: over 80 billion neurons and thousands of distinct cell types, all produced with remarkable precision across development. NSCs are the architects of this process, and their dysfunction has lasting consequences: disrupted NSC behavior can impair neuron production, alter brain architecture, and increase the lifelong risk of neurodevelopmental and neuropsychiatric disorders.
We focus on a question that is both fundamental and clinically urgent: how do NSCs integrate signals from their environment — including immune signals — to make the right decisions at the right time? And when this process goes awry, how does it contribute to disease?
Because the developing human brain is not directly accessible, we engineer advanced stem cell models that faithfully recreate key aspects of NSC biology. These platforms let us probe how immune environments and disease-associated perturbations shape stem cell function with precision and quantitative rigor.
OUR APPROACH
We build experimental platforms designed for causal discovery, moving beyond observation toward mechanism. Our core toolkit combines spatiotemporal gene control, human disease modelling, CRISPR–Cas9 genome engineering and functional screening to study regulators of NSC fate at scale.
Research Themes
1) Extracellular and immune signaling in neural stem cells
NSCs develop within rich, dynamic signaling environments and immune-derived signals are among the most powerful yet least understood inputs they receive. Our work centers on cytokine signaling, with a particular emphasis on type I interferon (IFN) pathways.
Type I IFN activation is a shared feature of conditions that increase neurodevelopmental risk, including viral infections during pregnancy, inborn errors of immunity known as Interferonopathies, and Down syndrome. We use these as windows into how immune dysregulation disrupts NSC biology. We address the following questions:
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How do NSCs sense and respond to cytokines at the molecular and cellular level? What governs their sensitivity and signaling dynamics, and how is this altered in disease?
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How are cytokine gradients established and propagated within NSC niches?
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Where do developmental and immune signaling programs converge within gene regulatory networks?
The goal is to define how immune dysregulation derails NSC development and identify strategies to restore normal function.
2) Microglia interactions with neural stem cells
Microglia — the brain's resident immune cells — colonize the developing brain remarkably early, sharing the same niche as NSC from the very start. Yet the molecular and cellular dialogue that orchestrates their co-development remains largely unexplored.
We are building the first in vitro models of NSC–microglia co-development to ask:
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How do microglia shape NSC fate decisions and developmental potential?
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Is this communication disrupted in neurodevelopmental disorders and could restoring it rescue normal developmental programs?
The goal is to map the cellular and molecular logic of NSC–microglia crosstalk and establish whether its breakdown is a driver of neurodevelopmental pathology.
Ultimately, we want to understand not only how the human brain is built but how it fails, and how those failures might be corrected. By combining precision perturbation tools, functional genomics, and spatially informed stem cell models, we aim to uncover the fundamental rules of human NSC biology and translate them into new strategies for intervention in neurodevelopmental disorders.