top of page
Research
Key Biological Questions
Define Neural Stem Cells
Our lab is driven by a fundamental question: How can we unlock the regenerative potential of the brain by reactivating dormant neural stem cells (NSCs)?
We study NSCs across health, aging, and disease to understand how their identity, function, and environment change over time. What defines an NSC—and how do intrinsic programs and extrinsic cues determine its fate? Why do NSCs become dormant with age, and can we reverse this process?
We are particularly interested in how NSCs behave in the context of neurodegenerative diseases such as Huntington’s Disease (HD), Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and brain injury. What is their identity in these disease states, and how does it differ from their healthy counterparts? How do human NSCs compare to those in mouse models?
We investigate how inflammation and immune cells - including microglia and T cells - interact with NSCs and influence their behavior. How does the aged or inflamed brain limit neurogenesis, and can immune modulation restore it? What neurotrophic factors drive NSC activation or maintain quiescence?
Finally, we seek to define the spatial and molecular signals that reawaken NSCs in vivo - and to harness those signals for therapeutic brain regeneration.
Summary of some of the most important questions:
What defines a neural stem cell (NSC), and how does this definition shift across health, aging, and neurodegenerative disease? Why do NSCs become dormant with age, and can this dormancy be reversed? What are the key intrinsic and extrinsic mechanisms that regulate NSC identity and fate? How do NSCs differ in the context of specific diseases such as Huntington’s Disease (HD), Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and brain injury? How similar are human NSCs to their mouse counterparts at the molecular and functional levels? What neurotrophic factors promote NSC activation versus quiescence? How does chronic inflammation reshape NSC behavior and regenerative potential? What is the nature of the interaction between NSCs and the immune system? How do NSCs communicate with microglia and T cells, and what are the consequences of this crosstalk in aging and disease? Can targeted immune modulation restore neurogenesis in the aged brain? And finally, what are the spatial, molecular, and cellular cues that enable the reactivation of dormant NSCs in vivo?
Modulate Neural Stem Cells
Our lab is focused on developing strategies to precisely and safely modulate neural stem cells (NSCs) for therapeutic purposes. We aim to transform NSCs from a dormant population into an active source of brain repair - without compromising safety, identity, or long-term stability.
We explore how small molecules and antisense oligonucleotides (ASOs) can reprogram or rejuvenate NSCs in vivo, and how repeated delivery might enhance regeneration over time. A key goal is to guide NSCs toward specific fates -neuronal or glial - on demand, enabling targeted repair based on disease context.
To do this safely, we are investigating how to promote controlled proliferation without triggering tumorigenesis, and how to reset or slow the NSC aging clock to restore their youthful potential. We also ask whether intercellular engineering - for example, reprogramming local microglia or T cells - can create a supportive niche that boosts NSC function and regenerative capacity.
Ultimately, we aim to build a toolkit for modulating endogenous NSCs in a way that is scalable, disease-specific, and clinically translatable.
Summary of some of the most important questions:
How can we therapeutically modulate neural stem cells (NSCs) in the aging or diseased brain? Can we design small molecules or antisense oligonucleotides (ASOs) to precisely control NSC behavior? Which ASOs are most effective for reactivating or reprogramming NSCs in vivo? Is it possible to safely repeat these interventions over time without diminishing their efficacy? How can we direct NSCs to generate specific neuronal subtypes or functional glia on demand? What strategies allow us to promote NSC proliferation without increasing the risk of tumorigenesis? Can we slow or even reverse the molecular aging clock of NSCs? Is it feasible to enhance NSC function by engineering their interactions with other brain cells, such as microglia and T cells?
Enhance Neural Stem Cells Based Therapy
Our long-term goal is to translate neural stem cell-based regeneration into real-world therapies for neurodegenerative diseases. To do so, we ask not only how to generate new neurons and glia, but how to ensure they are functionally integrated, long-lasting, and therapeutically meaningful.
We study whether the newly generated neurons are wired into existing circuits, whether they modify behavior, and how many cells are required to produce measurable clinical benefits. We also investigate potential side effects, such as aberrant differentiation, immune activation, or off-target reprogramming - critical concerns as we move toward human applications.
To improve safety and precision, we explore CRISPR-based genome and epigenome editing tools to fine-tune NSC behavior in vivo. In parallel, we are developing real-time tracking and control systems to monitor cell fate, integration, and function over time.
By combining NSC reprogramming with circuit-level delivery strategies and immune modulation, we aim to build next-generation therapies that do more than slow neurodegeneration—they reverse it.
Summary of some of the most important questions:
What constitutes an effective and safe NSC-based therapy for neurodegenerative disease? Are the newly generated neurons functionally integrated into existing circuits—and do they improve behavior? How many neurons or glia must be generated to achieve therapeutic benefit? What are the potential side effects or risks of in vivo reprogramming or NSC activation? Can we meaningfully improve neurological phenotypes, such as motor or cognitive function, in disease models? What strategies will allow us to translate these findings into human therapies? How are new neurons wired into existing neural networks—and can we guide or accelerate this integration? Can we use CRISPR-based tools to enhance the precision, safety, or scalability of NSC-based interventions? How do we monitor and control the long-term fate and function of regenerated cells in vivo? Can we combine NSC modulation with immune engineering or circuit-targeted delivery systems for enhanced efficacy?
bottom of page