1. The role of Arf family GTPases and their regulators in the control of cell migration and metastasis
The Arfs are a family of small GTPases that control many aspects of cellular function, including vesicular transport and cytoskeletal dynamics. Like other GTPases, Arfs require accessory proteins to activate them (guanine nucleotide exchange factors, or GEFs) and de-activate them (GTPase activating proteins, or GAPs). We recently discovered that one of the 15 human Arf GEFs, IQSec1/BRAG2, is overexpressed in a large fraction of breast and prostate cancers, where it regulates cell migration and consequently metastasis. We are currently working to understand how IQSec1 and its interacting partners control the disassembly of adhesions to the extracellular matrix, a process that is essential for cell motility.
2. The cell biology of bacterial pathogenesis
We are examining how the obligate intracellular pathogen Salmonella manipulates host cell cytoskeletal and membrane trafficking machinery to drive its uptake into non-phagocytic epithelial cells, and its survival inside both epithelia and macrophages. We use a combination of genetic, biochemical and morphological approaches (confocal, live cell microscopy, EM) and mouse models to define the roles of specific bacterial and host molecules in pathogenesis in vitro and in vivo.
3. The innate immune response to bacterial infection
We are also characterizing a novel pattern recognition receptor, BAI1, which mediates the clearance of Gram-negative bacteria by macrophages. We had previously shown that BAI1 recognizes the surface lipopolysaccharide (LPS) expressed by all Gram-negative species, and actively drives bacterial phagocytosis in macrophages. More recently we found that BAI1 not only mediates bacterial internalization, but is also required for the production of reactive oxygen species that ultimately kill internalized bacteria. We are currently working to define the signaling pathways that operate downstream of BAI1 and to define its role in bacterial clearance in vivo.
- BS, Biology, Southern Connecticut State University
- PhD, Cell Biology, Wesleyan Univeristy
- Postdoc, Cell Biology, Whitehead Institute
- Postdoc, Cell Biology, University of California, San Francisco
- Arf family GTPases and their function in membrane trafficking and cell motility
- Cell biology of bacterial infection
- The innate immune response to bacterial infection