Daniel Ojeda Juárez is a postdoctoral researcher in pathologist Christina Sigurdson’s group at the University of California, San Diego. There, he investigates the cellular mechanisms that drive neurotoxicity in human prion diseases, which ultimately lead to synapse loss, cognitive decline, and death. In this Postdoc Portrait interview, he shares how he thrives in the high-risk environment of working with prions.
Decoding Prion Neurotoxicity and Protein Aggregation
Q | What drew you to prions?
I have always been fascinated by complexity and have had a desire to understand the biological world. Growing up in Oaxaca, Mexico, I lived at the epicenter of both classic and emerging tropical diseases. Witnessing the outbreaks of HIV, Zika, Chikungunya, and H1N1, and seeing the catastrophic impact they had on the brain and its development, ignited my passion for neurobiology.
I was driven to understand how external pathogens and internal failures ravage the brain. This curiosity naturally drew me to the ultimate biological puzzles: prion and Alzheimer’s diseases. The fact that prions are inherently transmissible, coupled with growing evidence that amyloid-beta aggregates may share similar seeding properties, represents one of the great remaining mysteries of medicine. Deciphering the common language between these diverse proteinopathies may finally reveal the fundamental rules governing neurodegeneration.
Q | What scientific problem are you trying to solve?
Prion research is a high-stakes balancing act. Following tragic historical lab infections and the variant Creutzfeldt-Jakob disease outbreak, linked to bovine spongiform encephalopathy, stringent biosafety protocols have restricted our work to highly specialized, often isolated, facilities. This frequently limits the techniques and instrumentation we can apply to the disease.
My favorite project addresses this hurdle: I developed a novel induced pluripotent stem cell-derived neuronal model that successfully recapitulates pathological prion signaling without producing infectious aggregates. By decoupling the disease’s molecular signature from aggregate formation, this model allows us to utilize advanced imaging and analytical equipment previously off-limits, significantly accelerating our search for therapeutic targets in a safe, scalable environment.
Precision in High-Stakes Laboratory Environments
Q | What has been the most exciting part of your research journey?
The most exhilarating aspect of my career has been the time spent within biosafety level (BSL-2 and BSL-3) laboratories. Operating in these environments puts you in a unique mental and physical state. You are encased in Tyvek suits, face shields, and respirators, working with pathogens that demand absolute precision. There is a profound, meditative quality to the isolation; the steady hum of the biosafety cabinets, fans, and fridges, combined with the inherent risk, creates an atmosphere that is as thrilling as it is demanding.
It takes a specific temperament to thrive in such a sterile, highly coordinated, and solitary space. However, there is a distinct sense of freedom in that isolation. One of the best perks is the ability to truly immerse yourself in your work, usually with your favorite music echoing through the room, turning a high-pressure environment into a private concert.
Q | If you could be a laboratory instrument, which one would you be and why?
I would be a confocal microscope. My career has been driven by a desire to decode complexity, and in biology, the most profound way to understand a system is to truly see it.
As a confocal microscope, I would be the first to peer into the breathtaking architecture and spatial organization of the cell. I would witness, in full color and high definition, the individual molecular threads that weave together to create the vast, intricate tapestry of a living organism. To be the bridge between the invisible and the visible, capturing the exact moment where cellular structure meets biological function, that would be a sight to behold.
Responses have been edited for length and clarity.
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