Many blood cell disorders, such as leukemia, require bone marrow transplantation to treat them. This requires a genetic match from donor to patient, which is often impossible to find. If scientists were able to understand the full complement of genetic cues utilized to make blood stem cells during embryonic development, they could replicate this process in the test tube to generate perfectly matched stem cells for lifelong curative therapies. Dr. David Traver, Professor of Cellular and Molecular Medicine at the University of California, San Diego, studies the biology of stem cells, using zebrafish, a small translucent tropical freshwater fish. He and his team are working to understand how stem cells that generate all of the blood cells in our bodies for life are first born in the embryo. Answers to this question will have key implications in understanding how these rare but potent cells self-renew themselves, how they give rise to leukemia when deranged, and how we may replicate their normal development in the test tube to ultimately generate blood stem cells for any patient in need.

Dr. Traver and his team have pioneered the use of zebrafish to study the biology of blood-forming stem cells. They were the first to image directly the birth of these stem cells in their native environment due to the optical transparency of the zebrafish embryo. Despite the zebrafish’s many differences from humans, their genetic code is very closely related to humans. Therefore, the study of zebrafish can unravel mysteries about our own systems in novel ways. In addition, they have taken advantage of the powerful genetics of zebrafish to identify new, unexpected pathways that regulate stem cell emergence. In fact, thanks to their work, zebrafish are now used across the globe in labs that hope to see molecular processes from the outside of the fish. With a unique and creative approach to exploring how stem cells are made, Dr. Traver and his team have high hopes for future applications that include treatment, basic research, and exploratory projects as well.

Current research includes:

• How Stem Cells are Made: Dr. Traver and his team are primarily trying to understand how stem cells that make blood are born. Their research in the last five years has rapidly expanded with the hopes that they can harness new discoveries to ultimately replicate the normal development of hematopoietic stem cells in vitro. In so doing, they may help contribute to stem cell therapy for blood disorders to offer relief from symptoms and stress for patients and their families.

• How the Daughters of Stem Cells Provide Immunity: Dr. Traver is also interested in how stem cell progeny provide immunity. This interest has led to a number of projects with incredible applications in medicine that include:

  • Parasitic Worm Infections: Dr. Traver has developed a zebrafish model that can be infected with parasitic worms just as humans can. Approximately one-third of the earth’s population is infected with parasitic worms, leading to great suffering and mortality. He and his team are hoping to use this new infection model to identify new drug therapies that can be rapidly employed to help people.  

  • Leukemia: Using zebrafish models, Dr. Traver and his team are able to treat leukemic zebrafish with sophisticated chemical libraries to identify new drugs to eradicate human leukemia.

  • Autism Spectrum Disorder: Zebrafish are helping to investigate the function of microglia in the brain, a macrophage subset that plays a large role in many neurodegenerative diseases. Alongside his collaborator, Dr. Alysson Muotri, he is studying a severe form of autism called Rett Syndrome. By studying the mechanisms that lead to disease in vivo, Dr. Traver hopes to treat the excessive inflammation that appears to underlie the development of many ASDs.