We use planarian flatworms to understand the mechanisms of regeneration. Unlike more established model organisms, planarians rapidly regenerate all of their organs by activating an abundant population of pluripotent stem cells. These stem cells are the basis of the unlimited regenerative capacity of planarians, and consistently supply new cells that fuel animal homeostasis. Just as in mammals, injury stimulates unique cellular behaviors that lead to the restoration of functional organs. However, many questions remain as to how pluripotent stem cells are triggered to proliferate, how they “know” which tissues need to be replaced, and how they coordinate their activity to produce functional tissues. We interrogate gene function with a multidisciplinary approach that combines RNA interference (RNAi), behavioral analysis, cell biological experiments, and transcriptomics.
Project 1: Organ regeneration
The pharynx is the mouth of planarians. In the video below, the pharynx is the large, white tube that sucks up food into the animal’s body.
Project 1: Organ regeneration
The pharynx is the mouth of planarians. In the video below, the pharynx is the large, white tube that sucks up food into the animal’s body.
We discovered how to selectively remove this organ by soaking animals in sodium azide. We call this amputation strategy "chemical amputation" to contrast it with the typical "surgical amputation", which begins with a razor blade. Chemical amputation is precise, reproducible, and challenges stem cells to regenerate an entire new pharynx.
After removing the pharynx, the stem cells in the rest of the body are activated to regenerate a new pharynx. Our goal is to understand the molecular and cellular mechanisms responsible for pharynx regeneration. We are using functional genetics (RNA interference) and single-cell transcriptomics to identify genes involved in pharynx regeneration.
Project 2: Stem cell responses to radiation
Like any dividing cell, planarian stem cells are sensitive to DNA damage, most commonly delivered by radiation. Exposing planarians to radiation introduces double-strand breaks, preventing cell cycle progression and leading to rampant cell death via apoptosis. Because radiation potently induces loss of stem cells, much like it does in humans to mitigate tumorigenesis, we use radiation to study the cell biological effects of DNA damage. We discovered two ways of preventing this inevitable cell death. First, coupling injury with radiation causes robust stem cell persistence, but only locally, adjacent to the wound. We are very interested in the molecular and cellular mechanisms linking injury to apoptosis. Second, we discovered that knockdown of the ATM kinase – a PI3-like kinase that orchestrates DNA repair – prevents stem cell death after radiation.
After removing the pharynx, the stem cells in the rest of the body are activated to regenerate a new pharynx. Our goal is to understand the molecular and cellular mechanisms responsible for pharynx regeneration. We are using functional genetics (RNA interference) and single-cell transcriptomics to identify genes involved in pharynx regeneration.
Project 2: Stem cell responses to radiation
Like any dividing cell, planarian stem cells are sensitive to DNA damage, most commonly delivered by radiation. Exposing planarians to radiation introduces double-strand breaks, preventing cell cycle progression and leading to rampant cell death via apoptosis. Because radiation potently induces loss of stem cells, much like it does in humans to mitigate tumorigenesis, we use radiation to study the cell biological effects of DNA damage. We discovered two ways of preventing this inevitable cell death. First, coupling injury with radiation causes robust stem cell persistence, but only locally, adjacent to the wound. We are very interested in the molecular and cellular mechanisms linking injury to apoptosis. Second, we discovered that knockdown of the ATM kinase – a PI3-like kinase that orchestrates DNA repair – prevents stem cell death after radiation.
