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Ubiquitination in health and disease


Our research aims to unveil the diverse roles of ubiquitination in preventing or driving diseases. Ubiquitination is an essential post-translational protein modification required to maintain cellular homeostasis, and alterations in ubiquitin-dependent pathways have been implicated in the pathogenesis of several human diseases. However, ubiquitination is a highly complex process and various aspects of the ubiquitin system are not yet fully understood. Gaining insight into the cellular and molecular mechanisms of ubiquitination, as well as into its physiological roles is therefore critical on the path to designing novel treatments. Our team applies innovative techniques to model diseases and alter the functions of ubiquitin-related genes in order to reveal the underlying molecular basis of disease pathogenesis, primarily focusing on cancer, immunity and metabolism. Our ultimate aim is to provide novel opportunities for the development of more effective and specific therapeutic strategies.


Selected Publications

Gavali S, Liu J, Li X, Paolino M. Ubiquitination in T-Cell Activation and Checkpoint Inhibition: New Avenues for Targeted Cancer Immunotherapy.

Int J Mol Sci 2021, 22(19), 10800

Paolino M, Koglgruber R, Cronin SJF, Uribesalgo I, Rauscher E, Harreiter J, et al.

RANK links thymic regulatory T cells to fetal loss and gestational diabetes in pregnancy. Nature 2021 Jan;589(7842):442-447

Cronin SJF, Seehus C, Weidinger A, Talbot S, Reissig S, Seifert M, et al.

The metabolite BH4 controls T cell proliferation in autoimmunity and cancer.

Nature 2018 11;563(7732):564-568

Suriben R, Kaihara K, Paolino M, Reichelt M, Kummerfeld S, Modrusan Z, Dugger DL, Newton K, Sagolla M, Webster JD, Liu J, Hebrok M, Dixit VM. β-cell insulin secretion requires the ubiquitin ligase COP1. Cell 2015. 163 (6), 1457-1467.

Paolino M, Choidas A, Wallner S, Pranjic B, Uribesalgo I, Loeser S, Jamieson AM, Langdon WY, Ikeda F, Fededa JP, Cronin SJ, Nitsch R, Schultz-Fademrecht C, Eickhoff J, Menninger S, Unger A, Torka R, Gruber T, Hinterleitner R, Baier G, Wolf D, Ullrich A, Klebl BM, Penninger JM. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature 2014. 507 (7493), 508-512.


Paolino M, Thien CB, Gruber T, Hinterleitner R, Baier G, Langdon WY, Penninger JM. Essential role of E3 ubiquitin ligase activity in Cbl-b-regulated T cell functions. J Immunol. 2011, 186 (4), 2138-2147.

selected publ
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