Research

Systems control of stem cells for regeneration

One branch of our research seeks to unravel the cellular and molecular mechanisms that coordinate individual stem cells to optimize population functions.  Animals rely on stem cells for tissue growth, repair, and remodeling.  Stem cells are characterized by their capacity to self-renew and differentiate.  In addition, stem cell populations often diversify into a dynamic hierarchy of subpopulations that can differ both molecularly and functionally.  To maintain the proper balance of cell types within a tissue, every individual stem cell must decide when to divide, and what daughter cells to make.  Although these decisions can be fallible and sometimes even stochastic, the collective output at the whole population level must be robust to steady homeostasis but adaptive to physiological changes, such as growth and injury repair.

To discover the fundamental rules that integrate at the systems level the interactions between stem cells, their subpopulations, and their somatic contexts, we use quantitative fluorescence imaging and functional genomic analysis to study free-living flatworms, freshwater planarians (image below).  Planarians have the unique capacity to regenerate the entire body from small tissue fragments.  Their abundant but simple stem cell populations facilitate quantification and manipulation of stem cell behaviors throughout the whole body.

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Evolutionary cell biology of flatworms

Cell, as the basic unit of life, has been in a dynamic progression through evolution.  How does a cell type evolve from an ancestral cell type, contribute to a range of animal forms, and then convert to a new cell type for improved adaptation in new contexts?  What are the core attributes or constraints to define a particular cell type, and, inversely, what are the “extensions” that can be used to reprogram a conserved cell type for diverse physiological functions?  Our research seeks to answer these important questions, which have just become experimentally accessible as genomic technologies rapidly advance.

To directly access similar cells that have adapted to widely divergent contexts, we compare two evolutionary cousins, free-living flatworm planarians and parasitic flatworm schistosomes.  Our previous work showed that schistosomes and planarians possess similar stem cells that exhibit conserved molecular signatures.  While the planarian stem cells are used for tissue regeneration after injury, the schistosome stem cells fuel the complex parasitic life cycle by undergoing multiple rounds of proliferation and differentiation in transmission between hosts.  Using single-cell sequencing techniques, we seek to decipher the evolutionary relationships between these stem cell populations, and the adaptation of these cells to their drastically differing functions.

New pathways to eradicate infectious parasitic diseases

Our research explores basic flatworm biology to rationalize and facilitate discovery of new strategies to eliminate parasitic flatworm infections.  Among thousands of other flatworm parasites, schistosomes, commonly known as blood flukes, cause one of the most prevalent infectious diseases, schistosomiasis, from which over 230 million people suffer.  This disease imposes a global socioeconomic burden comparable to that of tuberculosis, HIV/AIDS, and malaria.  The inefficiency of current global efforts to eradicate this disease highlights an urgent need for a better understanding of schistosome biology.

flame_scaleOngoing projects in the lab take functional genomic and bioengineering approaches to deconstruct cell types that are flatworm-specific, physiologically vital, and easily accessible from the exterior.  Recently, we have developed pipelines to isolate targeted cells, and to identify essential molecular components that are also druggable.  For instance, shown above is an isolated flame cell, which bears a tuft of cilia that vibrates as a flicking flame creating a fluid current to push metabolic wastes and surplus water from the animal body to the exterior.  This invertebrate-specific cell type is essential to worm physiology as a primitive kidney.  Translating the interesting biology associated with these cells, we seek to contribute to better global health.