Anna Greka on mentors, superheroes, and a neglected disease

At a talk in the Broad Institute auditorium last spring, Anna Greka recounted a story from her childhood. The daughter of a kidney specialist, Greka learned about George, a boy her age who suffered from nephrotic syndrome, a debilitating kidney disease that often made him miss out on the usual adventures of childhood, instead keeping him tethered to a dialysis machine while he waited for a kidney transplant.

The story, and others her father shared, stuck with her. While studying to be a doctor, she found herself making connections between what she knew of nephrotic disease and the newest human genetic research that was coming out in the wake of the Human Genome Project. She also learned that little had changed in the kidney disease field in the intervening years. Today, Greka, who is an institute member at the Broad, an assistant professor at Harvard Medical School, and a nephrologist at Brigham and Women’s Hospital, is trying to change that. She’s taken a fresh approach to studying kidney disease that is yielding new leads in the search for much-needed treatments.

In this World Kidney Day edition of #WhyIScience, Greka talks about her work and what inspired her to pursue science as a career:

Q: How would you describe your life as a scientist?
A: I’m a physician-scientist, so I wear two hats. I treat patients with kidney conditions at Brigham and Women’s Hospital. When I’m not seeing patients, I am trying to discover new treatments for kidney diseases, which are on the rise worldwide but for which we have not developed any new therapeutic approaches in the last 40-50 years. More specifically, my lab studies rare, genetic forms of kidney disease to better understand the mechanisms that lead to kidney failure. That work led to our recent Science paper, which was a long-awaited game changer: we showed for the first time how to develop a targeted, mechanism-based therapy for a progressive kidney disease.

Q: What was new about your approach? And, what made you think it would work?
A: We focused on developing a treatment based on information from genomics and on molecular mechanisms—a genetically-inspired, mechanism-based approach, if you will. Inspired by what was known from human genetics about kids with inherited forms of nephrotic syndrome, we zeroed in on a molecule called Rac1. We found that Rac1 triggers another molecule called TRPC5 and the two together ignite an injury pathway in precious kidney cells called podocytes—and losing those podocytes eventually causes kidneys to fail. The most exciting discovery was that we found a candidate drug that can efficiently block TRPC5 and prevent podocyte loss. We tested it in many animal models and saw great results, so we are hopeful that one day in the not-so-distant future this might be a new treatment for patients with nephrotic syndrome and other kidney diseases.

Q: What got you interested in science?
A: My parents and early teachers got me interested in science. And, for as long as I can remember, I wanted to be a physician-scientist. There was a book, Arrowsmith, by Sinclair Lewis, a novel about a young physician-scientist in 1920s America. I knew when I read it that I wanted to be like him. It is interesting to re-read this book now (it got the Pulitzer Prize in 1926, but Lewis refused to accept it), as it appears to be current even today in the way it considers the challenges facing physician-scientists as they navigate a complex world of academia and pharma/industry in their quest to make a difference for patients.

Q: Were there any real-life historical figures who contributed to your decision to pursue your career?
A: Marie Curie. When I visit my kids’ school to talk with their class about what it’s like to be a scientist, one thing I always do is ask them who their favorite superheroes are. They say Batman or Superman, of course. Then I tell them that Marie Curie is my superhero! She’s still to date the only person, man or woman, with two Nobel Prizes in two distinct scientific fields—and of course she received this recognition at a time when science wasn’t a welcoming field for women.

Q: Do you feel that science is a welcoming field for women now?
A: Some people still put barriers in front of young women working in science and medicine, not necessarily intentionally, but because they have long held biases which are hard to change, mostly related to traditional male/female roles and balancing the demands of work and family. This creates challenges for young physician-scientists like me. I have learned, and I am continuing to learn, that persistence is the single most important trait for success.

Anna Greka with trainees from her lab at Harvard Medical School.

Q: Are there particular things researchers can do to make the field more welcoming for young scientists entering the field?
A: I’ve learned that one can be a mentor at any stage in one’s career. Spending the time and effort to hear someone out and try to guide them is critically important. Paying it forward is something I feel very strongly about. It is not only our moral obligation, but it also secures the future of our field and science at large. I have a program where I bring one top high school student from my old high school in Thessaloniki, Greece to my lab every summer. It brings me great joy to see them grow and blossom into successful students and young scientists as they have all gone on to places like Harvard, MIT, Columbia, Johns Hopkins, Brown, Williams, etc.

Q: On a broad scale, what would you like to see from scientific leadership in the future?
A: I’d like to see scientific leaders who are adaptable, agile, innovative, and fearless.