For Anna Greka, MD, PhD, the most gratifying part of her work as a physician-scientist is seeing the potential of her team’s efforts to help patients. While running a lab at the Brigham and the Broad Institute of MIT and Harvard, Greka continues to care for patients with rare kidney diseases in the clinic. Recognizing that patients’ stories can be a great motivator, she invites patients to meet with scientists in her lab and share their perspectives.

“We hear what is most important to them,” said Greka. “Patients have a chance to articulate what a possible treatment might look like and what they are hoping for. It’s a chance to help demystify the research process for patients and an incredible opportunity for scientists on our team to be inspired and reminded of our ultimate goal.”

Greka acknowledges that the research process can be slow, and that there are many false starts. But her team is determined to make progress.

“There are mountains of work that remain, but we’re excited about the possibilities that lie ahead,” she said. “One thing I emphasize to my colleagues who are at the early arc of their career is that curiosity-driven science, when done well, can lead you to wonderful discoveries, with unexpected benefits for science and for patients.”

Scientific Dual Citizenship

Today, Greka is an associate professor of Medicine, a physician in the Renal Division, and the director of the Kidney-NExT Center for Kidney Disease and Novel Experimental Therapeutics at the Brigham. She traces her journey back to her undergraduate days at Harvard when her interest in biomedical research was ignited by doing work in a Brigham lab. Greka also completed clinical rotations at the Brigham as part of her studies at Harvard Medical School. After concluding her clinical training at the Mass General and the Brigham, she embarked on her independent scientific career.

“I’m a physician-scientist and, by definition, wear two hats,” said Greka. “At the Brigham, I run a clinic where I see patients with difficult-to-treat kidney diseases who are referred to us from around the world. The Brigham is also where many of my collaborations begin, especially around patient samples. Building bridges between the Brigham and the Broad has been incredibly empowering in terms of collaborations, resources, and opportunities to grow my research program.”

In fact, Greka describes being a part of the Brigham and the Broad as having “scientific dual citizenship.”

“Our team of scientists working across the two institutions are integrated in a way that benefits our research and, hopefully, will ultimately benefit patients,” she said. “I am proud of our fearless attitude toward going into unknown territory to make discoveries, and I love our openness in collaborating with colleagues in all the other hospitals and institutions in our area. We’ve been able to develop collaborations with people across the entire Boston ecosystem, and across the world.”

The Realm of Research

Greka’s lab is focused on dissecting how mechanisms of cell homeostasis – the fundamental processes that maintain life – are disrupted in ways that lead to kidney and related degenerative diseases. By investigating diseases caused by genetic mutations – small errors in the DNA – the team is learning valuable lessons relevant not only to diseases of the kidneys but also disorders affecting many other organs throughout the body and across the human lifespan.

“Kidney diseases affect 850 million people worldwide and while there are a few drugs that can slow progression, there are none that can stop these diseases in their tracks,” said Greka. “We need a deep, mechanistic understanding of what goes wrong in order to develop targeted treatments that can stop or reverse these disorders.”

Currently, one area of intense focus for the lab is a newly discovered mechanism that controls the quality and trafficking of certain proteins inside cells. The team discovered a previously unknown way by which some misfolded, mutant proteins become toxic by accumulating in cells of the kidney, the eye, the brain, and more. Protein misfolding conditions are broadly known as proteinopathies and include prion diseases, Alzheimer’s disease, Parkinson’s disease as well as many rare or “orphaned” diseases. Most excitingly, the team has identified compounds that may reverse the harmful effects of toxic protein build-up.

“We are now hard at work figuring out how to advance our discoveries toward the clinic,” said Greka.

Never Losing Sight of Patients

Greka is the recipient of several accolades, including the 2018 Donald Seldin~Holly Smith Award for Pioneering Research. Most recently, she was named a National Academy of Medicine’s 2021 Emerging Leader in Health and Medicine Scholar for her extraordinary work in renal medicine.

“I’m so grateful for these honors, but it’s important to me to never lose sight of the most important stakeholders for everything that we do: our patients,” said Greka.

In her acceptance speech for the Seldin~Smith Award, Greka read from one of the letters she has received from patients over the years.

“This patient had sent me an old-fashioned, handwritten note and it meant so much to me,” said Greka. “Her letter was inspiring, motivating and a great reminder that all of our work—everything we do—is about the patients.”


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