Ryan Cupo was a graduate student in the Pharmacology Graduate Group from August 2015 to October 2021. He graduated from Alvernia University with a B.S. in Chemistry and Mathematics in 2015. During his undergraduate education, Ryan spent time in Gyorgy Hajnoczky's lab and Jim Eberwine's lab. Ryan is a Philadelphia Flyers fan and enjoys being outdoors, reading, and eating in his free time. In 2018, Ryan was awarded a Ruth L. Kirschstein National Research Service Award (NRSA) from the National Institute of Aging (NIA). Ryan also won the John S. O'Brien Award for best oral presentation at the annual PGG Retreat in 2018. In 2019, Ryan won a Blavatnik Family Fellowship in Biomedical Research. Ryan defended his Ph.D. thesis 'Discovery of a human mitochondrial protein disaggregase, Skd3'  in October, 2021.  In 2022, Ryan won the Saul Winegrad Award for best dissertation by a PGG student. Ryan went on to pursue his post-doc with Richard Youle at NIH.

Publications

D'Angelo, D., V.H. Sánchez-Vázquez, B. Cartes-Saavedra, D. Vecellio Reane, R.R. Cupo, H. Delgado de la Herran, G. Ghirardo, J. Shorter, R.A. Wevers, S.B. Wortmann, F. Perocchi, R. Rizzuto, A. Raffaello, and G. Hajnóczky. (2025). Dependence of mitochondrial calcium signalling and dynamics on the disaggregase, CLPB. Nat. Comm. 16:2810. pdf file link

Aikio, M.*, H.M. Odeh*, H.J. Wobst, B.L. Lee, Ú. Chan, J.C. Mauna, K.L. Mack, B. Class, T.A. Ollerhead, A.F. Ford, E.M. Barbieri, R.R. Cupo, L.E. Drake, J.L. Smalley, Y-T. Lin, S. Lam, R. Thomas, N. Castello, A. Baral, J.N. Beyer, M.A. Najar, J. Dunlop, A.D. Gitler, A. Javaherian, J.A. Kaye, G.M. Burslem, D.G. Brown, S. Finkbeiner, S.J. Moss, N.J. Brandon, and J. Shorter. (2025). Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy. Cell Rep. 44(1):115205. pdf file link (*Co-first author.).

Cupo, R.R., and J. Shorter. (2024). Decoding Skd3 (human CLPB): a mitochondrial protein disaggregase critical for human health. Isr. J. Chem. doi: 10.1002/ijch.202300153. pdf file link

Chuang, E., R.R. Cupo, J.R. Bevan, M.L. Rice, S. Mao, E.L. Gorenberg, K.L. Mack, D.M. Huryn, P. Wipf, J.L. Brodsky, and J. Shorter. (2024). Defining a small-molecule stimulator of the human Hsp70-disaggregase system with selectivity for DnaJB proteins. bioRxiv. doi: 10.1101/2024.01.11.575109. pdf file link

Mack, K.L.*, H. Kim*, E.M. Barbieri, J. Lin, S. Braganza, M.E. Jackrel, J.E. DeNizio, X. Yan, E. Chuang, A. Tariq, R.R. Cupo, L.M. Castellano, K.A. Caldwell, G.A. Caldwell, and J. Shorter. (2023). Tuning Hsp104 specificity to selectively detoxify α-synuclein. Mol. Cell. 83(18):3314-3332.e9. pdf file link (*Co-first author.).

Cupo, R.R.*, A. Rizo*, G.A. Braun, E. Tse, E. Chuang, K. Gupta, D.R. Southworth, and J. Shorter. (2022). Unique structural features govern the activity of a human mitochondrial AAA+ disaggregase, Skd3. Cell Rep. 40(13): 111408. pdf file link (*Co-first author).

Warren, J.T., R.R. Cupo, P. Wattanasirakul, D. Spencer, A.E. Locke, V. Makaryan, A.A. Bolyard, M.L. Kelley, N.L. Kingston, J. Shorter, C. Bellanné-Chantelot, J. Donadieu, D.C. Dale, and D.C. Link. (2022). Heterozygous variants of CLPB are a cause of severe congenital neutropenia. Blood. 139(5): 779-791. pdf file link

Cupo, R.R., and J. Shorter. (2020). Expression and purification of recombinant Skd3 (human ClpB) protein and tobacco etch virus (TEV) protease from Escherichia coli. Bio Protoc. 10(23):e3858. pdf file link

Cupo, R.R., and J. Shorter. (2020). Skd3 (human ClpB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations. eLife. 9:e55279. pdf file link

Eisner, V.*, R.R. Cupo*, E. Gao, G. Csordás, W.S. Slovinsky, M. Paillard, L. Cheng, J. Ibetti, S. R.W. Chen, J.K. Chuprun, J.B. Hoek, W.J. Koch, and G. Hajnóczky. (2017). Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity. Proc. Natl. Acad. Sci. U.S.A. 114(5):E859-E868. pdf file link (*Co-first author).

Lavorato, M., V.R. Iyer, D. Williams, R.R. Cupo, V. Debattisti, L. Gomez, S. De la Fuente, Y-T. Zhao, H.H. Valdivia, G. Hajnóczky, and C. Franzini-Armstrong. (2017). Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges. Proc. Natl. Acad. Sci. U.S.A. 114(5):E849-E858. pdf file link