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Next generation: Conchi Estarás

Estarás with her nephews and niece: Alex, Isabel, Miguel and Javi

Mallorca, a stunningly beautiful island lying off the east coast of Spain, is known for several distinctive exports. The red sausage sobrasada. Tennis great Rafael Nadal. Father Junípero Serra, who left the island in 1749 to make his mark in what would become California.

Now, some 240 years later, another ambitious Mallorcan has arrived on California's shores: Salk postdoctoral researcher Conchi Estarás. She's here to explore the inner workings of cellular machinery.

"I've always been curious," Estarás says with an infectious laugh, "even from the time I was a child. The telephone, the television— how does this work? I would always ask this. Then later, when I watched a caterpillar transform into a butterfly, I was completely fascinated. Metamorphosis is like magic for me. But tell me how it works!"

She's had to blaze that educational path for herself. No one in her family was interested in science: Estarás' mother is a seamstress and her father works in construction. None of h er three sisters has a bent for research. But Estarás, with her unflagging curiosity, simply had to know more.

Conchi Estarás

So after excelling in her undergraduate schooling, she went on to earn her doctorate at the Universitat de Barcelona in Spain. That's where she discovered that her innate curiosity was well suited to the field of molecular biology. "What I do is very mechanistic," she explains. "I like to learn how all the parts work together and to understand how one part directly influences another. In my studies I try to understand how everything works inside the cell."

Ever eager to expand her education, Estarás eventually packed her bags for the Salk Institute, where she found a mentor to guide further exploration: Kathy Jones, professor in the Regulatory Biology Laboratory. "Kathy has been wonderful," says Estarás. "She supported me in pursuing a new line of research within her lab."

That research culminated in a paper, recently published in Molecular Cell, with Estarás as the first author. In it, Jones and Estarás describe new details about stem cell growth that could bolster regenerative therapies to, for instance, create tissues for organ replacement, stroke victims and patients of other diseases.

They unveiled specifics about two cellular processes made up of clusters of signaling proteins, collectively called the Wnt and Activin pathways. These two processes work together to activate about 200 genes essential for stem cells to differentiate into cell precursors of a particular tissue, such as liver. The Wnt pathway initiates transcription and the Activin pathway increases the speed and efficiency of the cellular machinery. The team also learned that the Activin pathway was not effective unless the stem cells were first exposed to the Wnt signal. Additionally, they identified a connection to a third cellular signaling process, Yap, known to control tissue growth and organ size. Yap appears to buffer the effects of Activin in a late step of transcription. Better understanding these cellular processes will offer guidance for improving stem cell therapies to, for example, create effective replacement tissue for the lungs or pancreas.

"It's been a delight to work with Conchi to explore this emerging area of science," says Jones, "and amazing to see how quickly she has been able to discern unique aspects of the transcriptional environment."

The team's study has implications for cancer research as well. Wnt is known to turn on very early in human colon cancer, for example, and Activin-related transforming growth factor beta (TGF-ß) is tied to the metastasis of many cancers. Unraveling each gene's role in cancer could point the way to new therapies. "There is great interest in developing transcription-based inhibitors of the Wnt pathway," says Estarás, "because these would have strong anticancer activity for many tumor types."

In her free time—what little there is of it—Estarás will sometimes indulge in reading a mystery (no surprise there!) such as Isabel Allende's Ripper. She communicates regularly with her niece and nephews in Mallorca, claiming them as her "favorite hobby." And she also enjoys cooking. True to her independent nature, though, she doesn't follow a recipe. "I recently made moussaka," she says, "or at least, my version of it. I'm sure they do it differently in Greece. But people like mine a lot!" When asked if she finds similarities between cooking and scientific research, a mischievous gleam sparks her eyes. "First, I say 'no,' because that would mean that I don't follow protocol. But the truth is, when you get a protocol from someone else, you need to make it yours. You need to adapt it to your system and to your tools. So maybe the answer is 'yes.'"

She finds puttering in the kitchen to be relaxing, one of the few times of day she doesn't have to think about science. But often that's when breakthroughs happen. "Sometimes I'm in the lab 10 or 12 hours and I don't get any ideas," she says. "But when I go home and start cooking, it's suddenly like 'I know! I know!' And then I realize I do know how to further my project."

If her brain is sometimes resting, her vibrant personality is not. "I like going to work," she says. "The days I have more work are the days I enjoy better. But as the day progresses and there are failures, I start feeling like 'I don't want to do this anymore.' And by night I'm disappointed about everything. But the next day I wake up and think, 'Okay, maybe I can find a solution to this. Let's give it another try.'"

That sort of genial persistence might be a Mallorcan trait. Father Serra had it. Estarás' parents teach it. "You have to try to be the best at whatever you choose to do. That is what my parents always told me. It doesn't matter what you do. The important thing is just to try your hardest."

And that's what she's doing in her laboratory at the Salk Institute. "There's no place like Mallorca!" she proclaims. "But Salk is a wonderful place to make discoveries."