Exploring How Immune Defenses Change in Response to Evolving Viruses
Daniel Blanco-Melo, Evolutionary Virologist
Not long after he began his Ph.D. studies at the Aaron Diamond AIDS Research Center in New York City, Dr. Daniel Blanco-Melo found himself reconstructing the genome of a 30-million-year-old virus.
Just as paleontologists piece together the evolution of ancient life by studying fossils freed from rocks, the young molecular biologist was discovering the history of ancient pathogens from traces of viral genes woven into the DNA of primates, including humans.
“Viruses are able to get endogenized. By that, I mean they become part of the genome of the organism they infect. With time, some of these viral sequences were passed from generation to generation until this day, where they are now part of us.” Blanco-Melo said.
The virus he reconstructed was part of a line known as human endogenous retroviruses, the genetic remnants of which comprise about 8% of the human genome. Blanco-Melo concluded that this particular virus emerged in ancient monkeys 40 million years ago and faded out some 10 million years later — yet its history can be traced in the DNA of modern human beings.
Now a faculty member at Fred Hutchinson Cancer Center, Blanco-Melo is continuing his exploration of the evolution of viruses and of the immune defenses our bodies have used to protect against these microbial threats.
“By observing the history of viral evolution, we are gaining insights on the development of our own antiviral strategies," Blanco-Melo said.
One of his goals is to match our understanding of how viruses evolve with the parallel evolution of antiviral strategies of the immune systems of humans or our ancient primate ancestors.
Using a combination of molecular biology, genomics and advanced computational techniques, he is deepening our understanding of how evolving viruses interact with our ever-changing natural defenses against them. By observing the history of viral evolution, he is gaining insight on the development of antiviral strategies by the various components of the human immune system.
The ultimate goal is to uncover clues to better ways to stop diseases as varied as HIV/AIDS, influenza A and COVID-19.
Before joining the Hutch in November 2021, he worked as a postdoctoral fellow at the Icahn School of Medicine at Mount Sinai, in New York. There he was the lead author of an early analysis of immune responses to SARS-CoV-2, the virus that causes COVID-19. The paper found that the coronavirus elicits an imbalanced response, marked by low production of antiviral enzymes but high production of inflammatory molecules.
Blanco-Melo’s career took unexpected turns in its own evolutionary path. The son of architects in the colorful, nearly 500-year-old Mexican city of Puebla — at the base of the Popocatepetl volcano — he was groomed for a career in the same field.
“By observing the history of viral evolution, we are gaining insights on the development of our own antiviral strategies."
But serendipity intervened. One day, while he was still in high school, he gave his father as gift a popular science book, Matt Ridley’s “Genome: Autobiography of a Species in 23 Chapters.”
He cracked open the book himself and was hooked.
His focus on architecture began to shift, and when it was time for college, he chose the National Autonomous University of Mexico, which was building a world class program in genomics. He found that he fit right in. “As an undergrad, I was getting basically a graduate school-level education,” he said.
In retrospect, Blanco-Melo is not surprised that he ended up a scientist. A fan of movies, he was captivated as child by films as diverse as Jurassic Park, Back to the Future, and Raiders of the Lost Ark. The common thread is that the heroes were scientists.
“I was always drawn to the scientific characters, even in absurd movies such as Ghostbusters,” he said.
He has never dropped his interest in the arts. In New York he was a regular visitor to museums, where he favored the work of the early 20th century abstract painters. He and his wife — also a molecular biologist — are opera lovers and moviegoers.
Although he had seldom visited Seattle before he was recruited by Fred Hutch, he has been familiar with it since his college days. During a scientific meeting in Canada that he attended as an undergraduate, he met Hutch evolutionary virologist Dr. Harmit Malik, already a renowned expert in the field.
“We’ve had several conversations since 2009,” Blanco-Melo said. “Harmit is interested in a million things, and in parts of that, we kind of overlap. So, we have kept in touch.”
At the Hutch, he set up his own lab in the Steam Plant facility, which is designed to foster collaborative research throughout the center. Blanco-Melo has been building relationships with other Hutch experts, including virologists and data scientists.
“I guess it doesn’t matter what virus or theme I jump into next, there’s a person who is an expert at Fred Hutch,” he said.
— By Sabin Russell, January 24, 2022
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