Research

Our research is driven by the pursuit of new methods to answer fundamental questions in neuroscience. We focus on developing and applying pioneering technologies—from high-resolution functional ultrasound imaging to next-generation gene therapies—to overcome long-standing barriers in the field. This approach allows us to investigate the brain at multiple scales, aiming to bridge the gap between understanding its basic design principles and creating effective clinical applications.

Biotechnology

Our work develops next-generation biotechnologies aimed at repairing, rather than compensating for, disrupted brain function. We focus on advancing molecular and gene delivery systems, neuromodulation technologies, and translational safety frameworks that enable durable and precise interventions in the adult brain.

A central challenge for brain-targeted therapies lies in achieving long-term efficacy and safety across species with complex neural architectures. To address this, we are refining viral vector systems for stable gene delivery and minimal immune activation, and developing robust assays to assess treatment compatibility—such as improved neutralizing antibody detection for AAV-based therapies.

Because rodents do not fully recapitulate the organization or cognitive capacity of the human brain, we extend our studies to large-brained species, including cats and non-human primates. These models provide the necessary bridge between fundamental discovery and clinically viable approaches, guiding the development of biotechnologies capable of truly restorative outcomes.

Explore our current research projects in biotechnology

New Standard for AAV Neutralizing Antibody Detection

Enhancing the safety and effectiveness of gene therapy relies on accurately identifying which patients are suitable for treatment. This is often complicated by pre-existing neutralizing antibodies (NAbs) that can render adeno-associated virus (AAV) vectors ineffective, yet current detection methods are often unreliable and can lead to poor patient stratification. Addressing this critical gap, a new “Constant Serum Concentration (CSC)” AAV assay has been developed to provide more precise and reproducible measurements of NAb levels. This improved method significantly reduces misclassification rates by stabilizing the assay baseline, ensuring that patients are more accurately screened for therapy. This work represents a critical step forward, promising to improve treatment consistency and expand the applicability of AAV-based gene therapies.

Optimized Gene Therapy Delivery Method for Long-Term Brain Imaging

Genetically targeting specific brain cells is a powerful tool for understanding neural circuits and modeling diseases, but applying these techniques safely and effectively over the long term, especially in animals other than mice, remains a major hurdle. The use of gene therapy vectors, which are essential for this work, is often complicated by the body’s immune response and inconsistent gene activity, limiting the reliability and duration of experiments. This research directly tackles this challenge by systematically searching for an optimal delivery method. Through extensive long-term studies involving optical imaging and immune monitoring, an optimized gene therapy approach was identified that ensures stable, long-lasting gene expression for brain imaging while significantly reducing the immune reaction. This breakthrough provides a much-needed method for safe and stable genetic access to the brain, paving the way for more advanced and reliable long-term studies of brain function.

Healing

Why is it so difficult to cure diseases of the human brain?

The child’s brain is remarkably flexible – during development it constantly fine-tunes its neural connections: useful links are strengthened while unnecessary ones are eliminated. In adulthood, however, this flexibility – known as brain plasticity – is largely lost. As a result, the brain can no longer repair or reorganize its circuits after developmental disorders or mental illnesses, which contributes to the persistence of conditions such as amblyopia, attention deficit disorder, or depression.

Our research aims to understand how this “closed” state could be reopened and proper brain function restored in a targeted way. The key may lie in the brain’s mid-level – mesoscale – organizational units. These small, interconnected groups of nerve cells form a bridge between the cellular level and larger brain networks, playing a decisive role in how neural connections are formed and stabilized. If we can target and influence these units, we may be able to restore the adult brain’s ability to retune faulty connections – opening new possibilities for the treatment of developmental and mental disorders.

Explore our current healing research projects

Understanding “Lazy Eye”: How the Brain Predicts What We See

To explore how the brain predicts visual events and how this ability is affected in neurodevelopmental disorders, this research focuses on amblyopia, commonly known as “lazy eye,” as a model condition. The study uses an innovative virtual reality task where participants ride a stationary bike through a digital corridor while their brain activity is recorded with EEG. By introducing sudden, unexpected freezes in the visual motion, the experiment measures how the brain responds to these “prediction errors.” The primary goal is to compare these neural responses between individuals with amblyopia and healthy controls to pinpoint how the disorder impacts predictive processing in the brain. Ultimately, this work aims to build a functional model of the brain networks involved in visual prediction and to track how they change with treatment, providing new insights into which functions can be restored.

Uncovering the Brain’s Design Principles: How Global Maps Shape Local Circuits

A fundamental challenge in neuroscience is understanding how the brain organizes itself to process the vast amount of information in the visual world, especially in animals with sharp sight. The visual cortex contains specialized maps for different stimulus features, such as an object’s location in space and its orientation, but how these maps are arranged in three dimensions and interact has been poorly understood. This research employs high-resolution functional ultrasound imaging (fUSI), a technique that allows for detailed 3D mapping of brain activity across multiple scales—from entire cortical areas down to fine-grained functional structures. The key finding is that the brain’s large-scale map for visual space directly shapes the local patterns of neurons that detect orientation. This discovery provides crucial insight into the design principles of the visual system, explaining how it balances the need for a continuous global picture with the processing of fine local details.

High-Resolution 3D Brain Mapping with Functional Ultrasound Imaging

A persistent challenge in neuroscience is that traditional imaging techniques force a difficult trade-off: they can capture either high-resolution detail over a very small area or a broad view with low resolution. This limitation has made it difficult to fully map the intricate, three-dimensional ‘mesoscale’ architecture of the visual cortex, where complex circuits for processing sight are organized. To overcome this hurdle, this research employs a novel 3D functional ultrasound imaging (fUSI) method, a cutting-edge approach designed to generate high-resolution maps of brain activity across large volumes with excellent temporal precision, effectively resolving the classic trade-off. Applying this technique to the cat’s visual cortex, the study has successfully created detailed 3D reconstructions of functional maps for retinotopy and orientation preference, and has even identified specific features like orientation singularities, also known as pinwheels. This work provides an unprecedented window into the complex organization of neural circuits, significantly advancing our ability to understand how the brain processes visual information.

Animal models

Animal models that facilitate ideas/theories translating to therapies.

Animal models are essential for translating ideas about brain function into effective therapies. While mice have been invaluable for identifying fundamental mechanisms, their sensory and cognitive systems differ markedly from those of humans. For example, a mouse’s limited visual acuity makes it an inadequate model for studying higher-order visual processing or for developing therapies to restore human vision.

To overcome these limitations, we employ feline and primate models whose brain organization, sensory processing, and behavioral repertoires more closely mirror those of humans. These models allow us to both translate emerging biotechnologies—such as gene delivery systems and neuromodulation approaches—toward human application and investigate neural functions that cannot be meaningfully modeled in rodents.

By studying these complex brains, we bridge the gap between basic neuroscience and clinical translation, advancing our understanding of human brain function and paving the way for therapies that can achieve true restoration rather than compensation.

Explore our current animal-model research project

New Framework for Long-Term Neuronal Monitoring in Large Animals

Translational neuroscience, which aims to bridge the gap between basic research and clinical applications, faces a major obstacle: the difficulty of studying brain function in large-brained animals over extended periods. To address this, a novel protocol has been developed that combines high-resolution functional ultrasound imaging (fUSI) with electrophysiology to enable long-term, multimodal monitoring of neuronal activity. This approach allows for comprehensive analysis of brain function in the same subject over several months, which reduces data variability and minimizes the number of animals needed for research. The method’s success has been demonstrated through stable, reproducible recordings in cats, establishing a robust framework for longitudinal neuroscience studies. This breakthrough provides a scalable solution that overcomes the limitations of model scarcity and paves the way for more effective translational research.