Gopal Sapkota's Research Group

Pubmed | Biography


TGFβ and Wnt signalling in cells and disease

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.

Sapkota Lab

People

Polyxeni Bozatzi | PhD Student
Karen Dunbar | Postdoctoral Researcher
Luke Fulcher | PhD Student
Luke Hutchinson | PhD Student
Sascha Roth | Postdoctoral Researcher
Theresa Tachie-Menson | PhD Student
Kevin Wu | Postdoctoral Researcher

Selected Publications

Fulcher, L. J., Macartney, T. J., Turnbull, C., Hutchinson, L., and Sapkota, G. P. (2017) Targeting endogenous proteins for degradation through the affinity-directed protein missile system Open biology 7 170066
Fulcher, L. J., Macartney, T., Bozatzi, P., Hornberger, A., Rojas-Fernandez, A. and Sapkota, G. P. (2016) An affinity-directed protein missile system for targeted proteolysis. Open Biol 6
Rojas-Fernandez, A., Herhaus, L., Macartney, T., Lachaud, C., Hay, R. T., Sapkota, G. P. (2015) Rapid generation of endogenously driven transcriptional reporters in cells through CRISPR/Cas9 Sci Rep 5 9811
Herhaus, L., Perez-Oliva, A. B., Cozza, G., Gourlay, R., Weidlich, S., Campbell, D. G., Pinna, L. A., Sapkota, G. P. (2015) Casein kinase 2 (CK2) phosphorylates the deubiquitylase OTUB1 at Ser16 to trigger its nuclear localization Sci Signal 8 ra35
Vogt, J., Dingwell, K. S., Herhaus, L., Gourlay, R., Macartney, T., Campbell, D., Smith, J. C., Sapkota, G. P. (2014) Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling Open Biol 4 130210
Herhaus, L., Al-Salihi, M., Macartney, T., Weidlich, S., Sapkota, G. P. (2013) OTUB1 enhances TGFbeta signalling by inhibiting the ubiquitylation and degradation of active SMAD2/3 Nat Commun 4 2519