Ryan’s career and passion for science are driven by his desire to explore the unknown and ascribe molecular mechanisms to proteins. His most influential discovery, thus far, is that melanoma antigen (MAGE) proteins function as substrate-specificity factors in a novel family of multi-subunit ubiquitin ligases, called MAGE–RING ligases (MRLs). MAGE proteins have been examined as cancer biomarkers and targets for immunotherapy due to their specific expression and antigenic properties. However, their biochemical, cellular, and physiological functions had remained unknown. The discovery of the functions of MAGEs in ubiquitination opened a new area of research in ubiquitin biology and gave definition to this enigmatic protein family. Since this landmark discovery, Ryan’s laboratory has defined specific targets and functions of several MRLs, which has illuminated regulatory nodes with important implications. The group described the first ubiquitin ligase, MAGE-L2–TRIM27 MRL, which controls spatiotemporal actin assembly through non-degradative ubiquitination of the WASH actin-nucleating protein. Additionally, Ryan’s group discovered that the MAGE-A3/6–TRIM28 MRL ubiquitinates and degrades AMPK, a master regulator of cellular energetics. Ryan’s research has also substantially contributed to knowledge of human diseases. The group has shown that MAGEs are oncogenic drivers and have discovered a novel neurodevelopmental disorder caused by deletion of the MAGE-L2–associated USP7 deubiquitinating enzyme. In all, Ryan’s work has defined molecular functions of an enigmatic protein family, initiated a new field of study (i.e., MAGE proteins in ubiquitin biology), and highlighted the importance of MAGEs in disease.
Pineda, C.T., Ramanathan, S., Fon Tacer, K., Weon, J.L., Potts, M.B., Ou, Y.H., White, M.A., Potts, P.R. (2015) Degradation of AMPK by a Cancer-Specific Ubiquitin Ligase. Cell. 160, 715-28.
Hao, Y.H., Doyle, J.M., Ramanathan, S., Gomez, T.S., Jia, D., Xu, M., Chen, Z.J., Billadeau, D.D., Rosen, M.K., Potts, P.R. (2013). Regulation of Actin Polymerization and Retrograde Transport by Ubiquitination. Cell. 152, 1051-1064.
Weon, J.L., Yang, S.W., and Potts, P.R. (2018) Cytosolic iron-sulfur assembly is evolutionarily tuned by a cancer-amplified ubiquitin ligase. Mol. Cell. 69,113-25.
Lee, A.K., Klein, J., Fon Tacer, K., Lord, T., Oatley, M.J., Oatley, J.M., Porter, S.N., Pruett-Miller, S.M., Tikhonova, E.B., Karamyshev, A.L., Yang, P., Kim, H.J., Taylor, J.P., and Potts, P.R. (2020) Enhanced stress tolerance in germline stem cells through reduction of G3BP and suppression of stress granules. Mol. Cell. S1097-2765(20)30466-4.
Yang, S.W., Connelly, J.P., Porter, S.N., Kodali, K., Gan, H., Park, J.M., Fon Tacer, K., Tillman, H., Peng, J., Pruett-Miller, S.M., Li, W., and Potts, P.R. (2020) A Cancer-Specific Ubiquitin Ligase Drives mRNA Alternative Polyadenylation by Ubiquitinating the mRNA 3’-end Processing Complex. Mol. Cell. 77(6):1206-1221.e7.
Ph.D., Cell and Molecular Biology, UT Southwestern Medical Center
B.S., Biology, University of North Carolina- Chapel Hill