Cell migrations are a characteristic of multicellular life, both during development and malignant or, pathological states. A molecularly complex extracellular landscape plays a crucial role in directing migrating cells. One of the most complex structures in the extracellular space is heparan sulfate proteoglycans (HSPGs) that have been shown to be essential for cell-cell signaling. Here we propose to study the function of heparan sulfate proteoglycans in cellular migration using stereotypic cell migrations in the small nematode C. elegans which require HSPGs for function. To this end we are using an integrated approach that combines biochemical studies with genetic approaches to directly correlate protein and sugar structure of HSPGs with their function during cell migration. Our project will compare distinct cell migrations that we know already employ distinct molecular mechanisms, including distinct HS sugar structures. Lastly, we will define the global HS landscape that migrating cells encounter. To this end we will use a novel tool we have developed that allows the direct visualization of HS motifs in living animals. Our studies will allow correlating HS structure with cellular and subcellular localization. In summary, the proposed studies will provide insight into the cell-specific and sugar-dependent mechanisms that migrating cells use to interpret the extracellular space. Understanding fundamental aspects of cell-specific interactions of migrating cells may ultimately allow the cell-specific intervention during diseased states.

Public Health Relevance

Cell migrations are an important process during development and cancer where malignant cells migrate from the initial tumor to form metastases. Cells are guided by interactions with the extracellular environment, for example by cell-specific glycosaminoglycans, a complex class of sugar containing molecules. This proposal aims to understand the role that such complex sugars play in cell migration and to determine their structures. Understanding the function of these sugars may ultimately enable molecular interference with cell migrations in a cell-specific manner.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Intercellular Interactions (ICI)
Program Officer
Marino, Pamela
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Albert Einstein College of Medicine
Schools of Medicine
United States
Zip Code
Lázaro-Peña, María I; Díaz-Balzac, Carlos A; Bülow, Hannes E et al. (2018) Synaptogenesis Is Modulated by Heparan Sulfate in Caenorhabditis elegans. Genetics 209:195-208
Townley, Robert A; Bülow, Hannes E (2018) Deciphering functional glycosaminoglycan motifs in development. Curr Opin Struct Biol 50:144-154
Saied-Santiago, Kristian; Bülow, Hannes E (2018) Diverse roles for glycosaminoglycans in neural patterning. Dev Dyn 247:54-74
Saied-Santiago, Kristian; Townley, Robert A; Attonito, John D et al. (2017) Coordination of Heparan Sulfate Proteoglycans with Wnt Signaling To Control Cellular Migrations and Positioning in Caenorhabditis elegans. Genetics 206:1951-1967
Ames, Kristina; Da Cunha, Dayse S; Gonzalez, Brenda et al. (2017) A Non-Cell-Autonomous Role of BEC-1/BECN1/Beclin1 in Coordinating Cell-Cycle Progression and Stem Cell Proliferation during Germline Development. Curr Biol 27:905-913
Attreed, Matthew; Saied-Santiago, Kristian; Bülow, Hannes E (2016) Conservation of anatomically restricted glycosaminoglycan structures in divergent nematode species. Glycobiology 26:862-870
Desbois, Muriel; Cook, Steven J; Emmons, Scott W et al. (2015) Directional Trans-Synaptic Labeling of Specific Neuronal Connections in Live Animals. Genetics 200:697-705
Díaz-Balzac, Carlos A; Lázaro-Peña, María I; Ramos-Ortiz, Gibram A et al. (2015) The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM-EGL-15/FGFR Receptor Complex. Cell Rep 11:1377-84
Attreed, Matthew; Bülow, Hannes E (2015) A transgenic approach to live imaging of heparan sulfate modification patterns. Methods Mol Biol 1229:253-68
Díaz-Balzac, Carlos A; Lázaro-Peña, María I; Tecle, Eillen et al. (2014) Complex cooperative functions of heparan sulfate proteoglycans shape nervous system development in Caenorhabditis elegans. G3 (Bethesda) 4:1859-70

Showing the most recent 10 out of 11 publications