Faces of Discovery: Chaska Walton, PhD, and the Dawn of Living Therapies for Alzheimer’s Disease
The Buck Institute is at the forefront of unraveling the intricate mysteries of aging and pioneering innovative approaches to enhance human longevity and well-being. A cornerstone of this mission lies in the dedication and ingenuity of its scientists, whose groundbreaking work is highlighted in the monthly "Faces of Discovery" series on the Buck Blog. This installment delves into a two-part interview with research scientist Chaska Walton, PhD, a pivotal member of Julie Andersen’s lab and a recipient of a prestigious $2.4 million NIH Transformative Research Award. This significant grant, awarded to only nine researchers nationwide, underscores the transformative potential of Walton’s research in developing smart delivery systems designed to combat multiple pathologies associated with Alzheimer’s disease. Walton’s academic journey, marked by a PhD in molecular bioscience from CSIC/Autonomous University of Madrid, laid the foundation for his current work. In the first part of this interview, Walton articulated the personal drive and scientific imperative behind his pursuit of radically new Alzheimer’s treatments. Here, he offers an in-depth look into his laboratory endeavors and his vision for the future of neurodegenerative disease treatment within the next five to ten years.
A Journey of Discovery: From Fundamental Neuroscience to Engineered Therapies
Chaska Walton’s scientific odyssey has spanned continents, from the vibrant intellectual hubs of Barcelona and Madrid to the innovative research environment of California. This trajectory has been propelled by an insatiable curiosity about the human brain, a curiosity that has evolved from foundational neuroscience to the engineering of living therapies for neurodegenerative conditions. Walton’s early academic pursuits included studying psychology and neuroscience at the Autonomous University of Barcelona, a period that ignited a deep fascination with the complexities of neural function.
This foundational knowledge was further honed during doctoral work at the renowned Cajal Institute in Madrid. It was here that Walton, inspired by the forward-thinking vision of Ramón y Cajal himself—who posited that future scientific endeavors might overturn even his most firmly held beliefs—challenged long-standing scientific dogma. Walton’s groundbreaking research demonstrated that mature neurons, previously thought to be terminally differentiated and incapable of division, can re-enter the cell cycle. This discovery, a testament to the potential for biological recalibration, set the stage for his later work at the Buck Institute.
Upon joining the Buck Institute, Walton’s research focus underwent a significant shift. Moving beyond the exploration of neuronal vulnerability and the aging process, his work became increasingly centered on the design of synthetic immune-cell therapies for Alzheimer’s disease. This includes the development of programmable CAR-Treg (Chimeric Antigen Receptor Regulatory T cells) and sophisticated smart cell delivery platforms. Walton’s research is underpinned by a core conviction: that neurodegeneration is not an immutable consequence of aging but rather a biological process that can be rigorously interrogated, ingeniously engineered, and ultimately transformed. His work thus resides at the dynamic intersection of neuroscience, synthetic biology, and translational medicine, operating under the guiding principle that innovation thrives when boundaries are challenged and conventional rules are set aside.
Engineering Living Physicians: A Breakthrough in Alzheimer’s Treatment
Can you describe a recent experiment, breakthrough, or surprising finding in your work—and what it could mean for the future?
A particularly remarkable breakthrough we’ve achieved involves the genetic modification of cells to perform a dual function: detecting amyloid beta senile plaques, a hallmark of Alzheimer’s disease, and subsequently producing and secreting Leqembi, an FDA-approved antibody specifically designed to clear these plaques. This represents a profound shift, enabling cells to function as miniature, internal physicians.
Imagine shrinking your physician down to approximately 20 nanometers and imbuing them with extraordinary capabilities. A human physician, by their very nature, must rely on outward signs and symptoms, often waiting until a patient is demonstrably ill. By this point, depending on the specific pathology, the disease may have been progressing for days, weeks, months, or even years. Engineered cells, however, possess an unparalleled advantage: they can continuously scrutinize the body at a microscopic level, identifying pathological changes far earlier than any human observer. Furthermore, a human physician cannot deliver a drug to a single, affected cell. Engineered cells, conversely, achieve this level of precision with effortless ease. This breakthrough marks the initial steps toward a future where cells serve as our physicians, fundamentally redefining the perceived limits of medicine.
Explaining the Science: A Conversation with a Curious Grandmother
If you were explaining your research to a curious grandmother who hasn’t taken biology since high school, how would you describe it?
Essentially, we are working on teaching living cells to act like tiny doctors that reside inside our bodies. Normally, when we get sick, we rely on human doctors to identify the illness and prescribe medication. However, human doctors can only intervene once symptoms become apparent, and the medicines they prescribe often circulate throughout the entire body, affecting areas where they aren’t needed. My research focuses on engineering specific types of immune cells so that they can recognize the very early indicators of diseases like Alzheimer’s. These engineered cells can then release medicine precisely where it’s needed, and only when it’s needed.
Another critical aspect of diseases like Alzheimer’s is that they are rarely caused by a single issue. Instead, they are often a complex interplay of several problems occurring simultaneously. Conventional medicine typically addresses these issues one at a time. The cells we are engineering can be programmed to deliver multiple medications concurrently, functioning like a combination therapy that can tackle various facets of a disease all at once.
You can visualize this as equipping the body with a new, internal repair crew. This crew constantly patrols for problems, addresses them directly at their source, and ceases its activity once the job is completed. The ultimate aim is to detect diseases much earlier, treat them with greater precision, and transform conditions that are currently considered incurable into manageable or even curable states in the future.
Transforming Everyday Health: The Promise of Internal Therapeutic Systems
How might your work eventually affect people’s everyday lives, health, or understanding of the world?
The implications of this approach to medicine are profound and will dramatically reshape the landscape of everyday health. Currently, our reliance is on physicians to diagnose diseases after symptoms manifest and to prescribe medications that permeate the entire system. Our vision for the future involves the establishment of a secondary immune system, a living entity residing within us for a lifetime. Much like our natural immune system, these engineered immune cells will continuously monitor the body, detecting the earliest signs of disease long before any symptoms emerge. They will then deliver therapeutic agents with pinpoint accuracy to the affected areas. Because these are living cells, they possess the remarkable ability to self-renew, adapt to changing conditions, and remain active for years. This promises a future where protection is not contingent upon periodic clinic visits but is a constant, internal safeguard.
This paradigm shift also means that the body itself will become a manufacturer of many of the drugs it requires. Instead of enduring repeated purchases of expensive medications, or undergoing frequent infusions and injections, therapeutic molecules will be produced on demand within the body, precisely at the site of disease and for only as long as necessary. Treatment will transition from being an external product to an intrinsic function of the body.
Consequently, many of the diagnostic and treatment modalities currently employed by physicians and hospitals may become obsolete. Rather than diagnosing diseases late and reacting to accumulated damage, medicine will evolve into a proactive and continuous process. Individuals will likely require far fewer hospital visits, and the need for frequent imaging, blood tests, or repeated drug administrations for chronic illness management will diminish. Crucially, drugs will no longer flood the body, leading to debilitating systemic side effects. They will be produced locally and with exquisite precision. In this future, it’s conceivable that individuals could experience and overcome illness without ever consciously realizing they were sick.
The Next Frontier: A Self-Renewing Therapeutic Future
What excites you most about where your field is heading in the next 5–10 years?
I firmly believe that within the next five to ten years, the pioneering work being conducted in laboratories like ours will begin to introduce a transformative concept into mainstream scientific and public discourse: the idea that the future of medicine lies in the development of a secondary, engineered immune system capable of curing disease. What truly ignites my enthusiasm is not solely the prospect of building this sophisticated technology, but also witnessing the concept itself take root and gain widespread acceptance. The realization that a living system, residing within the body, could function as a self-renewing therapeutic entity—capable of detecting disease and responding automatically—will fundamentally alter society’s perception and approach to health.
This shift in understanding has the potential to unlock new avenues for addressing a vast array of chronic and age-related diseases, moving beyond the current reactive models of healthcare towards a future where proactive, internal defense and repair are the norm. The integration of advanced biological engineering with our innate biological systems heralds an era of unprecedented potential for human health and longevity.
