Research Themes
As a team we study the mechanisms of animal defense systems at the cellular level.
We value maintaining an inclusive and instructive environment in which we do our work.
Innate cellular defense systems
Larval immune cells stained for immune markers.
Juvenile stage of a transgenic ABCB1-/- L. pictus.
Our group is using the painted sea urchin, Lytechinus pictus, to explore fundamental mechanisms of innate immunity and its crosstalk with xenobiotic (chemical/toxicant) systems. L. pictus has a rich history in both developmental and environmental biology. The relatively short generation time (4-6 months) of this species allows us to 1) study the immune system from conception to metamorphosis (a significant developmental transition in many marine invertebrates); and 2) Generate transgenic animals for more mechanistic study of immune and xenobiotic pathways.
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Within this context, we are characterizing the innate immune cell types in L. pictus, with a focus on gut epithelial immunity. We also study the ATP-binding cassette families of xenobiotic drug transporters. ABC transporter genes are present in all kingdoms of the tree of life and enable the directed movement of small molecules across the cell membrane. These designated “xenobiotic” small molecules can occur naturally from dietary and bacterial by-products, or unnaturally, from anthropogenic pollution and industrial toxins. ABC transporters have been heavily studied in the context of driving acquired drug resistance in a cancer setting. However, their long evolutionary history and broad range of endogenous metabolic substrates suggest fundamental roles in both development and immunity.
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We hypothesize that ABCB1 plays conserved roles in the detoxification of bacterially-derived small molecules in gut epithelia. In all animals, the gut is colonized early and must tolerate commensal bacteria while remaining vigilant against pathogens. This must be upheld throughout the life of the organism. In the absence of ABCB1 in our model (sea urchin), mice, and man, gut tissues become inflamed and inflammatory bowel disease (IBD)-like phenotypes emerge. Using homozygous knockout ABCB1 lines in L. pictus, we seek to identify which bacterial products can be exported by host ABCB1, and how the build-up of those products triggers overactive host immune responses in the gut.
Protecting the primordial germ line
Most animals, including humans and sea urchins, set aside the primordial germ cells (PGCs) very early in embryonic development. These cells are the stem cells for making future egg and sperm in the fully developed adult form. It is well studied how these cells “close down” access to their DNA during their early development, in order to prevent mutations in the next generation. However, the fundamental protective mechanisms at the PGC membrane have yet to be described.
We seek to identify the key elements of the xenobiotic defense system that are active in PGCs. Comparative work with sea urchins and in-vitro derived human PGCL-like cells (hPGCLCs) enable us to define fundamental mechanisms at play. This work will also help us model their potential chemo-sensitization to toxicants--many of which are found at chronic "low dose" levels in ocean and human environments.
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This work is an extension of previous NIH F32 support to Dr. Schrankel.
Derived germ cells express a trio of transcription factors (PMRD1, SOX17, and TFAP2). We seek to study the localization and function of ABC transporters and other xenobiotic defense proteins in the human germ line.
