Where science connects with care: A Q&A with Leonard Zon

Leonard Zon in the lab

Leonard Zon, MD, is founder and director of the Stem Cell Research Program at Boston Children’s Hospital and an investigator with the Howard Hughes Medical Institute and the Harvard Stem Cell Institute. His laboratory research focuses on stem cell therapies for patients with cancer and blood disorders, using a high-throughput, automated system for screening potential drugs in zebrafish. Zon was cofounder of Scholar Rock and Fate Therapeutics and founder and past president of the International Society for Stem Cell Research.

Your hospital just received a #1 ranking from U.S. News & World Report. What does this mean relative to your role there?

I’ve been at Boston Children’s Hospital for 25 years, and it’s really satisfying to be at the premier institution for clinical care. And we’re very lucky to have one of the premier stem cell programs in the world. I have a strong sense that my impact on society is as a physician-scientist, bringing basic discoveries to the clinic. We’re able to have a huge impact on finding new diagnoses and new therapies for our children.

What inspires you to do your job every day?

As a hematologist I take care of patients who have devastating diseases – a variety of blood diseases and cancer. When I see these children, I’m always wondering, could there be ways to treating them that haven’t been thought of before? Successfully treating a child gives them an entire lifetime of health.

The mixture of science and medicine here is intellectually exciting, fun and satisfying – knowing that I am doing something important for patients.

Why is scientific research so important for a children’s hospital?

We have the best and brightest scientists in the world here coming to work on pediatric disease. I feel that everyone works really hard to deliver the best care to children, and the research often generates new ideas that could be transformational.

By having an excellent research operation, we have the ability to find new mechanisms involved in a disease and to translate that into finding new diagnostics and ultimately new therapies for patients.

How does that play out in stem cell research?

We have been able to generate stem cell lines from the skin or blood cells of patients who have a variety of different diseases — rare genetic diseases, blood diseases, immunodeficiencies and even very common diseases such as diabetes.

And with those lines we can begin to understand many aspects of these diseases, including finding chemicals or drugs that could be used to treat them. We’re very excited by the potential of this work to model any disease in a dish.

With stem cells, we also have the ability to generate new cells and tissues that could be put in the body to fix a diseased organ, and hopefully someday cure many patients from their diseases. We’re very lucky to have a unit in our midst that allows us to grow cells in a pristine way so that they could be given back to patients. We think stem cell therapies will develop over next 10 years.

Why do you do research in zebrafish?

Zebrafish have certain attributes that make them very powerful. The embryos are completely transparent, so you can see all the organs develop under a microscope, and every mother has 300 babies every week.

Leonard Zon explains zebrafish to Lieutenant Governor Timothy P. Murray
Zon shows then-Lieutenant Governor Timothy P. Murray around the zebrafish facility in 2013.

It’s very interesting to study the genetics of disease in these fish. We have made mutant zebrafish that have blood disease or that have cancer. This has allowed us to study the diseases and to find new treatments.

We have one of the largest zebrafish facilities in the world, with over 300,000 fish, and that allows us to do things more quickly. Several of the chemicals we have found to rescue disease in zebrafish also seem to be helping humans, based on clinical trials.

How is your work advancing clinical care for blood disorders?

We’re very interested in the process of marrow transplantation. A lot of patients receive a marrow transplant for a blood disease or for leukemia. This is actually curative, but 25 percent of patients actually die from this procedure. So there’s a great need to make it more safe.

Using our zebrafish models, we have discovered a drug in my laboratory that can increase the number of stem cells. And we’ve been using this drug clinically in patients undergoing marrow transplantation and cord blood transplantation. The results, based on early clinical trials, suggest that this is going to be very useful and help with the toxicity associated with marrow transplantation.

More recently, we have found a drug that can increase the ability of a stem cell to engraft. That means it will get into the marrow better and more quickly. This would allow the blood system to recover more quickly and ultimately help the patient. Once again, zebrafish gave us the clues:

In addition, we think that stem cell lines that come from patients could be used as an alternative source of blood stem cells. This would allow patients who do not have a perfect marrow match in their family to essentially receive a stem cell transplant from themselves.

This would allow the graft to occur without any toxicity. We’re very excited about this new approach and trying to pioneer it as we speak.

Visit the Zon laboratory.