General process for ligandomics to discover disease-selective drug targets and develop novel therapies. (A) Comparative ligandomics profiling to systematically map disease-selective ligands. (B) Function-first and/or therapy-first ligandomics approaches to independently characterize functional activity, disease selectivity, pathogenic role and therapeutic potential of identified ligands. (C) Drug development (PubMed).
Cell-cell communication is fundamental to the development and homeostasis of multicellular organisms. Of all intercellular regulations, cell surface ligand-receptor interactions are one of the most important signaling conduits to regulate a broad spectrum of cellular functions, ranging from stem cell niches and morphogenesis to disease and therapy.
Autocrine and paracrine factors connect ligand-secreting and responding cells, thereby holding the key to mapping precise pathways of intercellular crosstalk.
Ligand-receptor interactions can be amplified and ramified through multiple layers of intracellular signaling cascades to regulate a broad spectrum of cellular functions.
Therefore, pharmacological interventions directed at such early cell surface signaling events may be therapeutically more effective than interventions at locations further downstream. Indeed, 40% of all FDA-approved drugs target cell surface receptors.
However, only a limited number of extracellular ligands have been successfully exploited with approved drugs. This is probably because secreted ligands are more elusive and are traditionally discovered on a case-by-case basis with inherent technical challenges, whereas the human plasma membrane receptome has been fully mapped based on receptor transmembrane domains and cell surface expression.
Our ligandomics is the first technology to globally map cell-wide ligands, and our quantitative ligandomics can simultaneously quantify the binding or functional activity of entire ligandomes. Importantly, comparative ligandomics is capable of systematically profiling disease-selective ligands as high-quality drug targets to develop disease-targeting therapies with minimal side effects on healthy cells.
Our function-first and therapy-first ligandomics approaches are designed to independently characterize functional activity, disease selectivity, pathogenic role and therapeutic potential of identified ligands.
We are developing advanced ligandomics technology to further improve sensitivity, reliability and broad applicability of this new technology that will facilitate disease mechanism research and drug target discovery for both ocular and non-ocular diseases.
Our ligandomics project has led to issued patents. A startup biotech company is funded by a NIH business grant to further develop ligandomics technology.