Kevin Ryan - Publications#
10 MOST INFLUENTIAL PUBLICATIONS THAT ARE RESPONSIBLE FOR THE INTERNATIONAL RECOGNITION
(listed chronologically)
1) Crighton, D., Wilkinson, S., O’Prey, J., Syed, N., Smith, P., Harrison, P.R., Gasco, M., Garrone, O., Crook, T. and Ryan, K.M. (2006) DRAM – a p53-induced modulator of autophagy is critical for apoptosis. Cell 126(1): 121-134.
This seminal study described the first molecular link between tumor suppression and autophagy. It has been cited more than 1400 times and was highlighted in:
Cell
Nature Reviews Cancer
Science – STKE
Nature – Signaling Gateway
Faculty of 1000 Biology
2) Bell, H.S., Dufes, C., O’Prey J., Crighton, D., Bergamaschi, D., Lu, X., Schätzlein, A.G., Vousden K.H.and Ryan, K.M. (2007) A novel p53-derived apoptotic peptide de-represses p73 to cause tumor regression in vivo. Journal of Clinical Investigation 117(4) 1008-1018
This study delineated a mechanism to activate the p53-related protein p73 to cause programmed cell death and tumor regression in mice. It was highlighted in:
Science
BBC News
3) Wilkinson, S., O’Prey, J. Fricker, M. and Ryan, K.M. (2009) Hypoxia-selective macroautophagy and cell survival signaled by autocrine PDGFR activity. Genes & Development 23(11): 1283-1288.
With this study, Professor Ryan showed that there are signalling pathways in the cell that control the activation of selective forms of autophagy in response to specific stimuli. This showed that different forms of autophagy can be controlled independently of others.
4) Long, J.S., Crighton, D., O’Prey, J., MacKay, G., Zheng, L. Palmer, T.M., Gottlieb, E. and Ryan, K.M. (2013) Extracellular adenosine sensing – a metabolic cell death priming mechanism downstream of p53. Molecular Cell. 50(3):394-406
As cells frequently alter their metabolism during tumor development, it makes sense that sensing these changes would be connected to tumor suppression. This study described such a mechanism that is activated by p53 to detect extracellular adenosine – the backbone of ATP. The study was highlighted in:
Molecular Cell
Nature Reviews Cancer
Cancer Discovery
5) Rosenfeldt, M.T., O’Prey, J., Morton, J.P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T.S., Zheng, L., Ridgway, R., Adams, P.D., Anderson, K.I., Gottlieb, E., Sansom O.J. and Ryan, K.M. (2013) p53 determines the role of autophagy in cancer. Nature 504(7479):296-300
Autophagy is considered to both protect against and sustain tumour development. In this landmark study, Professor Ryan and his team showed that a single molecular event – loss of the p53 tumor suppressor – can cause a switch between these two functions of autophagy. The study was highlighted in:
Nature
Nature Reviews Cancer
Cancer Discovery
The New England Journal of Medicine
Nature – Science-Business Exchange (SciBX)
Faculty of 1000
6) Liu, E.Y., Xu, N., O’Prey, J., Lao, L.Y., Joshi, S., Long, J.S., O’Prey, M., Croft, D.R., Beaumatin, F., Baudot, A.D., Mrschtik, M., Rosenfeldt, M.T., Zhang, Y., Gillespie D.A. and Ryan K.M. (2014) Loss of autophagy causes a synthetic lethal deficiency in DNA repair. Proc. Natl. Acad. Sci. (USA) 112(3): 773-8.
As autophagy operates in the cytoplasm, it was a paradox why loss or inhibition of autophagy leads to DNA damage. This study provided an explanation of this effect by showing that loss of autophagy causes a defect in homologous recombination - an error-free mechanism of DNA repair.
7) Sakamaki J-I., Wilkinson S., Hahn M., Tasdemir N., O'Prey J., Clark W., Hedley A., Nixon C., Long J.S., New M., Van Acker T., Tooze S.A., Lowe S.W., Dikic I. and Ryan K.M. (2017) Bromodomain Protein BRD4 Is a Transcriptional Repressor of Autophagy and Lysosomal Function. Molecular Cell 66(4):517-532
The transcriptional regulation of autophagy was considered to be regulated by the TFEB transcription factor. Professor Ryan and his team showed however, that autophagy and lysosome genes are also controlled by the chromatin reader BRD4 in a manner independent of TFEB and its family memebers, opening up new critical control points in autophagy regulation. These findings were highlighted in
Faculty 1000
Autophagy
8) Sierra Gonzalez, P., O’Prey, J., Cardaci, S., Barthet, V.J.A., Sakamaki, J., Beaumatin, F., Roseweir, A., Gay, D., Mackay, G., Malviya, G., Kania, E., Ritchie, S., Baudot, A.D., Zunino, B., Mrowinska, A., Nixon, C., Ennis, D., Hoyle, A., Millan, D., McNeish, I.A., Sansom, O.J., Edwards, J. and Ryan, K.M. (2018) Mannose impairs tumor growth and enhances chemotherapy. Nature 563(7733):719-723.
Many tumors are addicted to glucose and targeting this dependency has long been considered a strategy for cancer therapy. Professor Ryan and his team discovered that the natural monosaccharide mannose can interfere with glucose metabolism to an extent that reduces tumour growth and enhances chemotherapy while having no negative effects on animal health. These findings have highly significant clinical potential and are currently being translated for clinical trial. The study received considerable attention and was highlighted in:
Cancer Discovery
Faculty 1000
40 news agencies worldwide, including BBC News and The Times
9) Beaumatin, F., O’Prey, J., Barthet, V.A.J., Zunino, B., Parvy, J-P., Bachmann, A.M., O’Prey, M., Kania, E., Gonzalez, P.S., Macintosh, R., Lao, L.Y., Nixon, C., Lopez, J., Long, J.S., Tait, S.W.G. and Ryan, K.M. (2019) mTORC1 activation requires DRAM-1 by facilitating lysosomal amino acid efflux. Molecular Cell S1097-2765(19)30551-9
The sensing of nutrients is fundamental to cellular growth, and a central regulator of the process is the kinase complex mTORC1. In this study, Professor Ryan showed that DRAM-1 – the lysosomal autophagy regulator previously identified by the Ryan group – is critical for the efficient activation of mTORC1 in response to amino acids.
10) Barthet, V.J.A., Brucoli, M., Ladds, M.J.G.W., Nössing, C., Kiourtis, C., Baudot, A.D., O’Prey, J., Zunino, B., Müller, M., May, S., Nixon, C., Long, J.S., Bird T.G. and Ryan K.M. (2021) Autophagy suppresses the formation of hepatocyte-derived cancer-initiating ductular progenitor cells in the liver. Science Advances 4(7):eabf9141.
Ductular reaction in the liver is a key stage in the development of hepatocellular carcinoma. This study reported that loss of autophagy causes ductular reaction, and this enabled Professor Ryan and his team to trace the origin of this effect and by association gain significant new insights into the cellular origin of hepatocellular carcinoma.
