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Alejandro Sánchez Alvarado Tackles an Unexplored Frontier in Biology – Regeneration

headshot of Alejandro Sánchez Alvarado
Alejandro Sánchez Alvarado, Ph.D. Credit: Stowers Institute for Medical Research.

Molecular biologist Alejandro Sánchez Alvarado is a rule breaker—from the animals he studies to understand regeneration, to the way he thinks scientists should best be trained, to his outlook on humans’ relationship to the natural world.

Sánchez Alvarado, Ph.D., has been recognized by his peers as a 2021 AAAS Fellow for his distinguished contributions to the field of animal regeneration. He is Executive Director and Chief Scientific Officer at the Stowers Institute for Medical Research in Kansas City, Missouri and a ​​Howard Hughes Medical Institute Investigator.

Sánchez Alvarado has identified dozens of crucial genes in certain planarians, tiny arrow-shaped aquatic flatworms known for their ability to regenerate body parts. His research team focuses on understanding how these creatures integrate their newly made parts into older, pre-existing tissues. And while it may be a long time, if ever, before humans can regrow body parts, Sánchez Alvarado and his team are showing how diseases may be better understood, and someday conquered.

“Regenerating neurons, for example, to restore axons in an individual with a severed spinal cord, the regeneration of neurons for treating stroke, or replace neurons that have Parkinson's or Alzheimer’s manifested in them; cardiac tissue, things that usually, when broken in our system, don't grow back. Those individual tissue types or cell types, I think the field is very close to being able to generate those,” says Sánchez Alvarado.

After studying mouse embryonic stem cells for his Ph. D. in pharmacology and cell biophysics, Sánchez Alvarado became fascinated with the potency of post-embryonic cells after witnessing tadpole tail regeneration as a postdoc at the Carnegie Institution of Washington in Baltimore. Now, the Sánchez Alvarado Lab explores the process and genetic control of regeneration and tissue maintenance.

His research model, Schmidtea mediterranea (flatworm), isn’t as widely used as Drosophila (fruit flies) or C. elegans (roundworm). But it has amazing abilities—if an adult worm is cut apart, almost any piece can form a new, fully functional animal within just two weeks.

“We needed to find an organism that exaggerates the biology we wanted to study, and then build on that biology. It turned out to be this very eclectic looking organism. We chose it because it had a relatively small genome, four pairs of chromosomes,” he adds.

Sánchez Alvarado credits the pioneering approach of his workplace for allowing him to pursue “big picture” questions in disease research and quality of life improvement. The Stowers Institute, a private biomedical research organization, receives 95 percent of its budget from an endowment. That avoids the often lengthy, and never certain, process scientists usually have to go through to secure government grants for new ideas.

“We are sniffing out new technologies, trying to find new things that we could use to try to address our problems. We can go from idea to experiment within days. It gives us a great deal of freedom to follow the trail of curiosity. And that's what I like about the Stowers Institute—that it allows us to really follow our noses. It is a true joy to be able to do science like that,” he says.

His non-traditional approach to scientific inquiry includes efforts to change the rigid way budding scientists gain their skills. He looks to the sports world for a radically different model.

“I'm a strong believer that we need to train our scientists the same way we train our baseball players. They’ve got to start playing games from day one. If we trained our baseball players the way we train our scientists, they would not play a baseball game until they were in their 30s. Who would want to go see those games?” he asks.

Sánchez Alvarado says STEM fields must also do a better job attracting young scientific explorers, regardless of their ethnic background or economic status. He says as a young Hispanic man he was exposed to inequities when he moved to the United States from Venezuela after high school.

“It took me a while to really wrap my brain around what it really means to be a minority, that not everybody has equal access to opportunities,” he remembers.

To help deal with such barriers, the Stowers Institute started a post-baccalaureate program for underrepresented minorities. College graduates with a degree in a STEM field spend a year in one of their labs, for research experience and academic mentoring. It comes with a generous salary to cover expenses. In such an environment, Sánchez Alvarado says the likelihood of identifying individuals who are going to be extraordinary scientists increases significantly.

While laboratory experience is crucial, Sánchez Alvarado also says a return to the natural world may help spark creativity in tackling chronic problems that we have not been able to resolve for centuries.

In the 19th and 20th centuries, he says, it may have been necessary to bring nature into the lab because of the complexity and fragility of laboratory equipment. But instrumentation is now extremely portable, so it’s time for a fresh look at how biology actually works in its natural environment.

Alejandro Sánchez Alvarado at Australian great barrier reef
Sánchez Alvarado on a field trip at the Great Barrier Reef in Australia.

“The answers to many of our questions have already been obtained by nature after four billion years of experimentation. Are we smart enough to identify them? Are we courageous enough, audacious enough to go out there and try to collect all this information? The world is not a Petri dish. It's not on a microscope slide. It is a creek. It is an ocean. It is a lake. It is a mountain. It is a park. That's where all these things are really unfolding right under our noses. It's humbling to see how complex nature is,” he notes.

Sánchez Alvarado often shares his awe and respect for nature’s defiant ones when engaging with others—the single celled organisms that became multicellular or those that moved from the ocean to land or to the air, for example.

“I think all these rule breakers are going to provide us with a great deal of insight into what those mechanisms are that make complex biological systems possible. I am a sucker for animals that did not get the memo and chose to do their own thing. To just break the rules and say—we don't care, we’re doing it this way,” he says.

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