Family loss spurs quest for knowledge

Finals week was just around the corner, and the pressure had become unbearable. Rodrigo Baltazar-Nuñez, then a freshman at the University of California, Los Angeles (UCLA), was barely coping with the chaos unleashed by the COVID-19 pandemic — the possibility that the University would evacuate the campus dorms loomed over him like a dark cloud. Just when he thought things couldn’t get worse, he got a call from his mother.

His grandmother had passed away. 

It felt as though the Earth had shifted on its axis. “Doctors said she had gone into liver failure,” recalls Baltazar-Nuñez. “But I didn’t understand — wouldn’t she have had severe symptoms if the disease was that advanced?”

Rodrigo Baltazar-Nuñez (right) with Manuel Leonetti (left) at CZ Biohub San Francisco.

Since then, profound grief, a sense of helplessness, and a yearning for closure have shaped Baltazar-Nuñez’s path toward pursuing science. Now, as a research associate in the lab of Manuel Leonetti, who heads the Intracellular Architecture group at Chan Zuckerberg Biohub San Francisco, Baltazar-Nuñez is contributing to the team’s cell biology research, seeking to understand processes underlying human diseases. He describes this work as a crucial step in his pursuit of a career in medicine, where he hopes to leverage his personal and professional experiences to mitigate health inequities and help those affected by chronic diseases.

“Rodrigo is incredibly passionate about understanding how the human body works and how these functions are disrupted in disease,” says Leonetti, also director of systems biology at CZ Biohub SF. “I think he’ll make a fantastic physician and scientist, and I’m very excited to be a part of his journey.”

Searching for closure in science journals

By the time Baltazar-Nuñez was five, he accompanied his parents to every medical appointment. Unlike other preschoolers who would play in the waiting room, his responsibility was enormous. With his eyes darting between his parents and the doctor, he assumed the role of translator, trying his best to understand medical jargon in English and find a way to express it in Spanish.

Over the years, Baltazar-Nuñez’s medical vocabulary expanded exponentially, but he grew no more comfortable in his role as interpreter and caregiver to his parents. Instead, with each visit, the stress of delivering serious health diagnoses ate away at him. But there was little choice — his parents were undocumented immigrant farmers from Mexico with no health insurance, relying on whatever help they could get from free community clinics in Visalia, a city in California’s agricultural hub, supported by private donations and volunteers.

The lack of health insurance, coupled with significant language barriers and financial constraints, meant that his grandmother, who lived down the street and helped to raise him and his three siblings, also struggled to access medical care.

“But I remember she was always just really tired,” says Baltazar-Nuñez. “We thought maybe she had some kind of gastrointestinal illness.”

By the time she was finally able to see a doctor, years later in Mexico, it was already too late. Over the course of a decade or so, her body had been fighting a silent battle with fatty liver disease, which eventually progressed to cirrhosis by 2020.

To Baltazar-Nuñez, it was painfully clear that his grandmother’s death was the result of not receiving adequate medical care when she desperately needed it. “If she would’ve been able to see a doctor regularly to monitor her health, maybe she’d still be here,” he says.

Spurred by this realization, Baltazar-Nuñez joined a campus organization called Compas during his freshman year at UCLA, which uplifts immigrant communities with limited access to healthcare. “We taught people how to take blood pressure readings and do basic clinical care like measuring their blood sugar,” he says. “These are things they otherwise would have had to pay for out-of-pocket in a clinic, and many of these families just can’t afford that.”

But there were still too many unanswered questions around his grandmother’s illness and death. What Baltazar-Nuñez needed most was clarity.  “I spent months reading journal article after journal article about liver disease, heart disease, and other related conditions,” he recalls. “I think it was a way for me to find closure by understanding scientifically what was going on in my grandmother’s illness.”

This eventually led him to the Tarling and Vallim Labs at UCLA, which jointly investigate how cells and tissues in the body manage fat breakdown and storage in conditions like fatty liver disease.

As an undergraduate research fellow in the Tarling-Vallim Labs, Baltazar-Nuñez’s project used a mouse model to explore the roles of three genes linked to fatty liver disease, which scientists suspect may play a crucial role in regulating metabolism. By deactivating these genes using CRISPR-Cas9 technology, his research aimed to deepen our understanding of how mutations in these genes — which interact within a biological pathway — affect liver function.

Carving a path to health equity

At CZ Biohub SF, Baltazar-Nuñez is now leveraging his training in genetic engineering to help the Leonetti Group in mapping the internal architecture of cells at the level of specialized compartments known as organelles. These structures perform essential tasks that ensure the cell functions smoothly. Mitochondria, for example, act as the cells’ powerhouses, while nuclei store genetic instructions that guide cell growth and reproduction.

By deconstructing cells piece by piece, the team aims to understand cell dysfunction at a granular level — an issue that underlies many chronic illnesses like cancer, diabetes, neurodegeneration, cardiovascular diseases, and autoimmune disorders.

Rodrigo Baltazar-Nuñez (right) with Camille Januel at CZ Biohub San Francisco.

Working under the guidance of scientist Camille Januel on the Leonetti team, Baltazar-Nuñez is helping to uncover mechanisms underlying neurodegenerative disease – and in particular,  Alzheimer’s disease (AD) – using organelle profiling methods that have been developed by the team.

Most days, he’s focused on generating and maintaining large populations of induced pluripotent stem cells (iPSCs), which are crucial for his team’s experiments. Derived from patients’ skin or blood samples, these immature stem cells possess the remarkable ability to develop into any cell type in the body, but preparing them for experiments is no easy feat — Baltazar-Nuñez routinely sequences their genetic data and compares the results across multiple cell populations to ensure they’re free of mutations that might otherwise compromise the reliability of the team’s experiment results.

“We’re talking about hundreds and hundreds of samples that have to be processed in parallel, which is extremely challenging technically,” says Leonetti. “It takes a village to do this work in a coordinated manner, and Rodrigo is an absolutely essential part of this effort.”

Using CRISPR-Cas9 technology, he tags each organelle within the iPSCs with a different fluorescent protein, enabling him to track their behavior once AD-linked genetic mutations are introduced. Once these cells pass his quality control checks, Baltazar-Nuñez carefully matures them in the lab, guiding their development into neurons over a challenging process lasting two to three weeks. This is where the excitement begins — by employing advanced cell imaging techniques, he can then observe real-time changes in the organelles in response to genetic mutations.

Januel says she has been pleasantly surprised by how quickly he’s learned, especially since he only recently traded mice for cell culture. “He joined our lab just after graduating from undergraduate, so he’s at the beginning of his career,” she says. “We’re all impressed by his skill, and also his enthusiasm and curiosity and his willingness to help make the work really rewarding and enjoyable. There’s no doubt he will have a nice and bright scientific career.”

While his ultimate goal is medical school, conducting research that has the potential to reshape our understanding of chronic illnesses, along with being a part of Biohub’s scientific community — where like-minded individuals are dedicated to advancing human health rather than being driven by financial incentives — fills him with hope for a future where health disparities aren’t so stark.

“Most of all, there’s always something new to learn here and someone to teach you,” he says. “It’s one of the most remarkable aspects of the Biohub culture that will always resonate with me.”