Research in the Wattrus Lab
During development and regeneration, cell division, differentiation, and death all occur simultaneously within similar and divergent populations. These cell fates must be balanced and coordinated to successfully generate and pattern new tissue. How does the organism determine which cells ‘win’ and which cells ‘lose’ in these processes? How does this vary between species with different regenerative capacities?
Our research efforts center on the clonal dynamics of stem/progenitor cells and the interactions they have with the immune system during development and regeneration. We aim to understand the mechanisms by which specific cells are eliminated and others are supported by immune cells, with the goal of exploiting unique molecular mechanisms to target specific cells for removal or expansion. We use the zebrafish (Danio rerio) as our primary model organism. Zebrafish are highly regenerative and are able to efficiently repair damage to their heart, brain, spinal cord, and more. They also offer a unique and powerful experimental toolkit and are amenable to high-throughput chemical and genetic screens, sophisticated embryological manipulation, genetic perturbation, and high-resolution imaging. Zebrafish embryos develop and regenerate rapidly and are optically transparent, which allows for unparalleled live observation of cell-cell interactions across multiple stages of development and injury repair. These advantages allow us to investigate fundamental biological questions in ways that would not be possible in other systems.
We also employ the use of the Japanese rice fish Medaka (Oryzias latipes) as a secondary fish model which has a significantly reduced regenerative capacity. In contrast to zebrafish, medaka generate scar tissue after injury to their cardiac and central nervous systems. However, medaka and zebrafish have similar physiology, can swap transgenic tools, and tolerate interspecies transplantation. We use both species as twin model systems to interrogate fundamental aspects of scarring and regenerative outcomes to injury.
Biography
Sam Wattrus received his A.B. in Human Developmental & Regenerative Biology in 2016 from Harvard College. As an undergraduate he worked with Dr. Amy Wagers and Dr. John Gurdon to study aging in skeletal muscle and cellular reprogramming in Xenopus laevis. In 2022 he completed his Ph.D under the supervision of Dr. Leonard Zon at Boston Children’s Hospital. His graduate work focused on developmental hematopoiesis and the stem cell niche in zebrafish. In 2023 he began his independent laboratory at Massachusetts General Hospital.
Dr. Wattrus is a Junior Fellow in the department of Molecular Biology at Massachusetts General Hospital, Lecturer in Genetics at Harvard Medical School, and affiliated faculty in the department of Stem Cell and Regenerative Biology at Harvard University. His work has been recognized in the Forbes 30 under 30 Science list.