Zebrafish in the Zon laboratory allow researchers to visualize drug responses at a single-cell resolution.
Principal Investigator
Leonard Zon, M.D.
The Zon laboratory aims to dissect how assaults to the hematopoietic system cause severe diseases such as leukemias, lymphomas, and anemias. They investigate hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish.
Leonard Zon, M.D.
- Professor of Stem Cell and Regenerative Biology
- Grousbeck Professor of Pediatrics
Harvard Medical School - Executive Committee Chair
Harvard Stem Cell Institute - Director
Stem Cell Program at Boston Children's Hospital - Investigator
Howard Hughes Medical Institute
Dr. Leonard I. Zon is the Grousbeck Professor of Pediatric Medicine at Harvard Medical School, an Investigator with the Howard Hughes Medical Institute, and Director of the Stem Cell Program at Children’s Hospital Boston. He received a B.S. in chemistry and natural sciences from Muhlenberg College and an M.D. from Jefferson Medical College. He subsequently did an internal medicine residency at New England Deaconess Hospital and a fellowship in medical oncology at Dana-Farber Cancer Institute. Dr. Zon is the former President of the International Society for Stem Cell Research, President of the American Society for Clinical Investigation, Head of the external investigators of the Zebrafish Genome Institution, and Chair of the Harvard Stem Cell Institute’s Executive Committee.
Dr. Zon is internationally recognized for his pioneering research in the new fields of stem cell biology and cancer genetics. His current research focuses on two critical avenues of investigation: identifying the genes that direct stem cells to become cancers or to develop into more specialized blood or organ cells, and developing chemical or genetic suppressors to cure cancers and many other devastating diseases.
Lab Overview
Each day, humans require the production of about one hundred billion new blood cells for proper hematopoietic function. Assaults to the hematopoietic system can cause severe diseases such as leukemias, lymphomas, and anemias.
As a lab we are dissecting hematopoietic development and disease using chemical screens, genetic screens, and analysis of novel transgenic lines in zebrafish. In addition we are validating and expanding our findings in mouse, human cell lines, and induced pluripotent cells.
There are still many outstanding questions about how hematopoietic progenitor cells are induced from vascular precursors, how hematopoietic stem cells (HSCs) home to and engraft into their stem cell niche, what genes controls stem cell self renewal and differentiation, what goes awry in blood cancers and diseases, and how to improve treatments such as bone marrow transplants. Hematopoiesis is well conserved in the zebrafish, which is a wonderful system for studying all of these processes. Zebrafish lay hundreds of embryos a week, develop red blood cells within 24 hours, and are transparent, which means that we can observe the blood cells as they develop and differentiate. A chemical screen recently found that prostaglandins upregulate blood stem cells, and this drug is now in clinical trial to improve engraftment of HSCs upon bone marrow transplant.
Our lab created the first animal model of a BRAF-driven cancer in 2005 with the publication of our Tg(mitf:BRAFV600E);p53-/- zebrafish melanoma model. Using this model, we identified an important epigenetic regulator, SETDB1, that is amplified in some human melanomas and which accelerates melanoma onset in our fish and has identified a novel approach to treat melanomas through targeting of their neural crest phenotype by repurposing an FDA-approved drug, leflunomide.
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How do prostaglandins and other factors enhance HSC production?
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Visualizing HSC engraftment into the niche using novel transgenic lines
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Screening for factors that improve HSC engraftment in a transplant model
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Chemical screening to improve anemic blood cells
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Understanding the genetic and epigenetic regulators of all steps of hematopoiesis