Angata's Lab - Research

Research

Current Projects

Identification of Siglec Ligands

To understand how the interaction between a Siglec and its binding partner (i.e., ligand) translates to biological outcomes, it is necessary to identify the physiological ligand. However, this is challenging because the Siglec–ligand interaction is generally weak. To facilitate the identification of physiological Siglec ligand, we developed a proximity labeling-based method. Cells that express Siglec ligand are labeled with Siglec–peroxidase complex and incubated with biotin tyramide and hydrogen peroxide to generate short-lived tyramide radicals, which covalently label the proteins nearby. Biotinylated proteins (ligand candidates) are enriched, and identified by mass spectrometry-based proteomics. This method enabled us to identify physiological ligands for Siglec-15 (1), Siglec-14 (2), and Siglec-7 (3).

Reference publications:

Roles of Siglec-15 in tumor microenvironment

Siglec-15 is a signaling molecule that associates with adapter protein DAP12 and tyrosine kinase SYK, to transduce a signal that facilitates the fusion of osteoclast precursors (1). We have shown that Siglec-15 is also expressed on tumor-associated macrophages, and that the interaction between tumor-associated glycan epitope and Siglec-15 may modulate the properties of tumor-associated macrophages (2). A study by another group suggested that Siglec-15 is also expressed on cancer cells, and modulates the activity of T cells in the tumor microenvironment (3). We are attempting to understand the roles of Siglec-15 in tumor microenvironment, and which model is relevant in what context.

Reference publications:

Role of Siglec-14 in inflammatory disease

Siglec-14 is a signaling molecule expressed on myeloid lineage of leukocytes, and also associates with adapter protein DAP12 and tyrosine kinase SYK. We previously found that the genes encoding Siglec-14 and its sibling molecule Siglec-5 (SIGLEC14 and SIGLEC5, respectively) are recombined in some people, and the resulting fusion gene (SIGLEC14-SIGLEC5) encodes a protein identical to Siglec-5 (1). We and others also found that this polymorphic “Siglec-14 deficiency” makes people more resistant (2) or sensitive (3) to certain bacterially induced clinical conditions. Using genetically engineered mouse model, we are investigating the details of the mechanism by which the presence or absence of Siglec-14 influences inflammatory disease.