Signal transduction pathways triggered by the transforming growth factor beta (TGFβ), bone morphogenetic protein (BMP) and Wnt ligands control a plethora of cellular processes throughout metazoan development and adult life. In humans, aberrations in these signalling cascades result in many diseases, including skin and bone disorders, fibrosis and cancer.
Our group studies the molecular mechanisms that underpin the regulation of TGFβ and Wnt signalling pathways. We are also involved in developing innovative technologies in order to address fundamental research questions and help expedite drug discovery. Much of our work revolves around reversible protein ubiquitylation and phosphorylation processes.
Recently our group has identified crucial roles of the SMAD1-interacting protein FAM83G, which we termed PAWS1 (Protein Associated With SMAD1), not just in non-canonical BMP signalling, but also in transcription, cell proliferation, migration as well as Wnt signalling. PAWS1 is a member of the poorly characterised FAM83 family of proteins that are connected through the conserved DUF1669 domain of unknown function. We are beginning to uncover common and unique physiological roles for each of the FAM83 members. In the coming years, we aim to delineate the molecular function and regulation of PAWS1 in cells and diseases, and understand how the DUF1669 domain controls the function of PAWS1 and the FAM83 family of proteins.
See below for current PhD projects available in the Sapkota lab;