Untangling the brain:
How do billion of cells connect with such precision via trillions of interactions to assemble the human neural circuits? This question remains central as we strive to understand the patterns of connections that determine our thoughts and behavior along with neural circuit assembly errors, which could result in neurological disorders - ranging from autism to mood disorders. Protocadherins are cell surface proteins that allow neurons to discriminate between self and non-self contact and prevent them from entanglement. We study the interactions of protocadherins to understand how ~50 protocadherin proteins provide neurons with the unique surface identity essential for their function.
Cell surface and secreted proteins comprise 1/3 of the human proteome and are vital to multi-cellular processes as they recognize and integrate signals arising from the extracellular environment. Yet current experimental high throughput methods are inadequate in defining interactions involving these proteins. To address this challenge, we are developing computational methods that utilize structural and non-structural information that aim to accurately predict protein-protein interactions.
Protein-protein interactions underlying immune response:
Immunotherapy agents targeting immune checkpoint inhibitor pathways and unleash anti-tumor immunity has revolutionized the treatment of human cancer. The unique and enticing prospect of such treatments resides in their ability to induce durable responses among different types of cancers. However, durable responses are only achieved for a limited number of patients. In light of this we are working on identifying and characterizing new immune pathways.