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Receptor tyrosine kinase signaling in epithelial homeostasis and transformation

Epithelia line the body cavities, glands, and surfaces straddling the interface between the external and internal environments. Consequently, epithelia are exposed to a continuous barrage of biologic, chemical, and mechanical insults and perhaps as a result more than 90% of human cancers are of epithelial origin. The Singh lab studies epithelia in normal and diseased states, like cancer, with a focus on key signaling events via the EGF receptor family of receptor tyrosine kinases (RTKs).

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Our research interests can be divided into two broad areas:

  • Trafficking of EGFR ligands in polarized epithelial cells

  • Resistance to EGFR-directed therapies in colorectal cancer

MMP EGF EGFR_edited.jpg

All EGFR ligands are synthesized as transmembrane precursors. Metalloproteases (ADAMs/MMPs) cleave the ligands to release them in extracellular medium. Ligands then bind and activate the receptor. Cell-surface ligand delivery and cleavage are thus critical steps in EGFR signaling.

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