Gopal Sapkota's Research Group

Sapkota Lab Website | 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.

 

See below for current PhD projects available in the Sapkota lab; 

Investigating the druggability of undruggable targets using the affinity directed protein missile system (AdPROM) in neurodegenerative disorders.

How do FAM83 proteins streamline Casein Kinase 1 (CK1) signalling in cells?

Clockwise from back left: Kevin Wu, Polyxeni Bozatzi, Luke Fulcher, Gopal Sapkota, Luke Hutchinson, Karen Dunbar, Sascha Roth, Theresa Tachie-Menson
Clockwise from back left: Kevin Wu, Polyxeni Bozatzi, Luke Fulcher, Gopal Sapkota, Luke Hutchinson, Karen Dunbar, Sascha Roth, Theresa Tachie-Menson

People

Bill Carton | 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., He, Z., Mei, L., Macartney, T. J., Wood, N., Prescott, A. R., Whigham, A., Varghese, J., Gourlay, R., Ball, G., Clarke, R. G., Campbell, D. G., Maxwell, C. A., and Sapkota G. P. (2019) FAM83D directs protein kinase CK1α to the mitotic spindle for proper spindle positioning. BiorXiv 480616
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Fulcher, L. J., Bozatzi, P., Tachie-Menson, T., Cummins, T. D., Wu, K., Dunbar, K., Shrestha, S., Wood, N., Weidlich, S., Macartney, T. J., Varghese, J., Gourlay, R., Campbell, D. G., Dingwell, K. S., Smith, J. C., Bullock, A., and Sapkota, G. P. (2018) The DUF1669 domain of FAM83 family proteins anchor Casein Kinase 1 isoforms. Sci signalling 11:531 eaao2341 DOI: 10.1126/scisignal.aao2341
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Bozatzi, P., Dingwell, K. S., Wu, K., Cooper, F., Cummins, T. D., Vogt, J., Wood, N., Macartney, T. J., Varghese, J., Gourlay, R., Campbell, D. G., Smith, J. C., and Sapkota, G. P. (2018) PAWS1 controls Wnt signalling through association with casein kinase 1α. Embo reports e44807 DOI 10.15252/embr.201744807
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Cummins, T. D., Wu, K. Z. L., Bozatzi, P., Dingwell, K. S., Macartney, T. J., Wood, N. T., Varghese, J., Gourlay, R., Campbell, D. G., Prescott, A., Griffis, E., Smith, J. C., and Sapkota, G. P. (2018) PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP. J Cell Sci Jan 10 131(1)
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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
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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 DOI: 10.1098/rsob.160255
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