In overlooked cellular connections, this researcher charted Zika’s path to the placenta

admin By admin 2025 年 10 月 16 日

A few months into his postdoctoral research at Baylor College of Medicine in 2021, Rafael Michita made a curious observation. Peering at Zika viruses infiltrating placenta cells under a microscope, he noticed thin filaments connecting infected cells to their neighbors.

“When I discussed this finding with my lab mates, they weren’t sure if these connections were worth studying further,” said Michita. “But I thought, they cannot be nothing. I was new to the field and wanted to dig deeper.”

Michita had come to Baylor from Brazil, where he had specialized in genomic studies correlating genetic variation to pregnancy disorders. Although this project was his first deep experience in cell biology, he had a nagging conviction that these intercellular conduits were key to Zika virus biology.

Now, Michita, who was recently named a STAT Wunderkind, is a trailblazer in the study of maternal-fetal viral transmission.

The filaments Michita observed, known as tunneling nanotubes (TNTs), are exploited by viruses such as HIV, influenza A, and SARS-CoV-2 to move between cells while evading immune detection. His research is among the first to suggest that TNTs may also provide a route for viruses to breach the placenta—a barrier that normally shields the developing fetus from pathogens.

He also demonstrated that Zika virus uses nanotubes not only for cell-to-cell spread but also to siphon mitochondria from healthy cells into infected ones, potentially fueling additional rounds of infection. Together, these discoveries point to new therapeutic strategies aimed at blocking viral transmission and safeguarding the fetus.

“Tunneling nanotubes are a very out-of-the-box concept that, at first, wasn’t accepted by researchers. They needed more proof,” said Olena Shtanko, an assistant professor in the Host-Pathogen Interactions Program at the Texas Biomedical Research Institute, who discovered that Ebola virus uses TNTs to travel through its host.

The role mitochondria may play “adds to our understanding of what we need to target to stop viral replication. TNTs are not going anywhere, and I think we’re going to see a lot more evidence that they contribute to viral pathogenesis.”

### ‘He Was Onto Something Exciting’

Beginning in the early 2000s, tunneling nanotubes were identified in human cells as a form of direct communication that transfers signaling molecules, nutrients, and organelles over long distances. TNTs were also observed in cancer, where they facilitated the transfer of mitochondria from healthy cells to malignant ones, exhausting the body’s antitumor response and boosting cancerous growth.

Despite these discoveries, it has taken years to apply these findings more broadly to viruses, which seem to co-opt TNTs in a similar way.

When Michita began his research with Zika virus, reports of virus-induced TNTs were so limited that he first encountered the concept of these cellular connections in the context of cancer.

“I think, initially, there was some disconnect between classical virologists and cell biologists. We use some cell biology, but we’re not trained to recognize tunneling nanotubes,” said Shtanko, who noticed that her colleagues would exclude images of TNTs from their publications.

“They thought these tubes made cells look distorted and ugly, and so were intentionally omitting them from pictures.”

Indira Mysorekar, a professor at Baylor College of Medicine who leads the laboratory that Michita works in, credits his expansive curiosity and knowledge for drawing connections between cancer growth and viral infections.

“I remember [a few months after joining the lab], he wanted to talk about a new project and this entity he had read about. I had never heard of tunneling nanotubes, but he had become very interested in thinking about whether they could be playing a role in the placenta, in terms of viral infections,” she said.

“I knew right away he was onto something exciting. He looks at everything holistically. He looks at what has been done in the past, what is out in the literature, what are the key questions coming in the future, and is able to integrate them in a very thoughtful, rigorous way. Which is exactly all the key features that we see in great scholars.”

### Diving Deeper into Zika

Michita attributes his inquisitive nature and eye for detail to his multicultural upbringing in Brazil and travels as an adult. His grandparents, who immigrated to Brazil from Japan, cultivated his sense of exploration—especially his grandmother, who was an elementary school teacher.

“I grew up in the countryside and was always running around in the wild,” he said. “I would say that we didn’t have a lot of friends, but I had a lot of books. I was always interested in nature, biology specifically.”

Michita, who entered university at 16, completed most of his studies in Brazil but also spent time abroad. After his sophomore year, he lived in New Zealand for a year and a half, working on a kiwi farm while learning English.

During his Ph.D., he spent two years in Germany, where he not only picked up the local language but also received specialized training in the immunogenetics of organ transplantation.

“It’s important to move and get exposure to new things,” he said. “We should not stop trying to improve as a person because there is always something new to discover.”

In Brazil, Michita became fascinated by the scientific and societal significance of pregnancy, focusing on uncovering the genetic factors that govern the delicate interplay between mother and fetus. As with an organ transplant, the mother’s immune system must accept the fetus—even though it contains non-self genetic material—for a healthy pregnancy.

“I believe this is one of the most interesting questions in biology, not only scientifically but also in terms of the perpetuation of our species,” said Michita, who demonstrated how breakdowns in immunotolerance can lead to miscarriage and preeclampsia, a serious pregnancy complication.

“Even before beginning this journey, I was aware of how poorly pregnancy-related diseases are understood, and I sensed that my research could help bridge this gap, impact clinical practice, and improve maternal health.”

Although Michita was making progress, he found himself increasingly drawn to new questions and innovative ways of looking at biological problems, rather than focusing on pure genetics.

This shift was accelerated by the Zika virus epidemic that swept through Brazil in 2015 and 2016. As research teams scrambled to analyze tissues from infected mothers and their babies, he saw firsthand how science could not only connect genes to health outcomes but also uncover the deeper cellular and molecular processes underlying the disease.

For Michita, the urgent search to explain how the virus spread from mother to fetus and caused birth defects such as microcephaly spurred fresh ways of thinking.

“The lack of understanding of how the virus infects the placenta, coupled with the unsettling reality that there is no cure for Zika virus, made it clear that I needed to expand my skill set to answer these and other pressing questions,” he said.

Michita, who had specialized in genetic association studies but never had the opportunity to work in cell biology, later added, “When I arrived in [Indira Mysorekar’s] lab, that’s when my academic motivation really sparked again.”

At Baylor, Michita joined one of the world’s most advanced laboratories for studying Zika virus infection. From a broad clinical perspective, scientists were analyzing placental samples from infected mothers and testing experimental treatments in mouse models.

They were also zooming in further, tracking the molecular cascade of infection in real time using cells plucked from fresh placentas and grown as two-dimensional sheets in Petri dishes, as well as in organoids—three-dimensional miniatures of the original organ.

Just as importantly, Mysorekar empowered scientists to think big, develop their own ideas, and incorporate their research into the greater infrastructure that the laboratory provided.

“Maternal and fetal health, pregnancy health, is Rafael’s core passion. But he knows that all different aspects are important in this field,” said Mysorekar.

“He’s the rare scientist who bridges disciplines—virology, immunology, mitochondrial biology, and maternal-fetal medicine—with creativity and rigor.”

### A Lab of His Own

In the next two years, Michita plans to launch his own laboratory. Backed by the NIH Pathway to Independence Award, he is broadening his research beyond Zika virus to include HIV, another pathogen capable of crossing from mother to fetus during pregnancy.

His early experiments have suggested that HIV-infected immune cells also use TNTs to spread into placental cells. He is also probing how TNTs develop, with the aim of creating a widely applicable therapy that targets vulnerabilities shared by viruses exploiting these nanotubes.

In Zika virus research, his work has zeroed in on NS1, a protein essential for TNT formation. Encouragingly, disabling NS1 in pregnant mice shielded their pups from birth defects.

When thinking about what’s next for virology and TNTs, Michita is guided by an early experiment with NS1.

To observe the protein’s action in real time, he and his lab mates genetically modified placental cells to produce NS1 tagged with a red fluorescent protein. Huddled together in the darkness of the microscopy room, they watched as a constellation of glowing proteins came to life, ruffling the cell membrane and sprouting connections to neighboring cells.

“We could see NS1 traveling through TNTs. The movement was so clear, how they were traveling from one cell to another,” said Michita.

“So far, we’ve studied just one aspect—viral proteins and mitochondria—but there is much more to be done. It’s an exciting and growing field.”
https://www.statnews.com/2025/10/17/rafael-michita-wunderkinds-zika-hiv-virus-research-placenta/?utm_campaign=rss

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