Research
Proper biological development of all multicellular animals requires precise communication between different cells, referred to as intercellular signaling. Intercellular signaling is instructed by ligands, which are proteins that are typically secreted outside the cell into the extracellular space where they serve as ‘messages’ to cells, and aberrant intercellular signaling causes diseases like cancer. The availability of extracellular ligands is a key determinant of intercellular signaling, and proteins called glypicans, which sit on the cell surface, interact with the ligands in the extracellular space to modulate their availability. My long-term goal is investigate glypican biology to uncover novel mechanisms via which glypicans establish and facilitate intercellular signaling during development and tumor progression.
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Our lab focuses on understanding glypican-based mechanisms of extracellular distribution of the evolutionarily-conserved Wnts, which play an important role in devlopmnent and tumorigenesis. Dally-like protein (Dlp) represents the fly ortholog of mammalian glypicans 1, 2, 4, and 6. Dlp acts as an exchange factor, analogous to pinball flippers on the cell surface, that keeps secreted Wingless (Wg)/Wnt1 moving in the extracellular space, available for signaling. It ensures that sufficient ligand is available for signaling away from source cells, and ectopic signaling is inhibited near the source cells to promote proper tissue development.
Research focus 2: How does Dlp communicate with endocytic machinery to ensure its proper cell-surface levels?
Dlp’s cell-surface localization is dynamic, and its cell-surface levels determine proper ligand distribution. This projects will focus on understanding molecular mechanims of Dlp trafficking.
Research focus 2: How do glypicans facilitate cytoneme function?
Wnts and other ligands can be ‘hand-delivered’ to target cells from source cells via cytonemes, which are actin-rich filopodia-like structures. Cytonemes cannot extend over cells that are mutant for Dlp, and cells lacking glypicans produce cytonemes that are shorter in length, compromising Wnt signaling. This projects focuses on undertsanding molecular mechanims of glypican-mediated function of cytonemes.
Resources: In addition to resources at UMass Lowell, trainees at UMass Lowell can acess core facilities available at other UMass campuses (UMass Boston, UMass Med School, UMass Amherst).
Research focus 2: How does Dlp communicate with endocytic machinery to ensure its proper cell-surface levels?
Dlp’s cell-surface localization is dynamic, and its cell-surface levels determine proper ligand distribution. This projects will focus on understanding molecular mechanims of Dlp trafficking.
Research focus 2: How do glypicans facilitate cytoneme function?
Wnts and other ligands can be ‘hand-delivered’ to target cells from source cells via cytonemes, which are actin-rich filopodia-like structures. Cytonemes cannot extend over cells that are mutant for Dlp, and cells lacking glypicans produce cytonemes that are shorter in length, compromising Wnt signaling. This projects focuses on undertsanding molecular mechanims of glypican-mediated function of cytonemes.
Resources: In addition to resources at UMass Lowell, trainees at UMass Lowell can acess core facilities available at other UMass campuses (UMass Boston, UMass Med School, UMass Amherst).