Age related diseases
Autophagy is a fundamental asset ensuring proteome plasticity against aging and age-related diseases. The Cenci lab pursues the goal to understand, and devise new strategies against, diseases of aging by investigating the mechanisms whereby autophagy maintains cellular homeostasis, with the paradigmatic age-onset cancer, multiple myeloma, as a privileged model.
A variety of funded projects address multiple intersections of autophagy with protein homeostasis and the biology of the endoplasmic reticulum and mitochondria, in search of new targetable cancer vulnerabilities and pathomechanisms of aging amenable to therapeutic manipulation.
The lab’s research recently expanded to explore the biological superpowers behind the exceptional longevity of bats, the only flying mammals, virtually exempt from age-related diseases, in primis cancer. AIRC and EU-funded projects investigate the interplay between autophagy, protein and organelle homeostasis, and innate immunity in bat cells.
Fucci C, Resnati M, Riva E, Perini T, Ruggieri E, Orfanelli U, Paradiso F, Cremasco F, Raimondi A, Pasqualetto E, Nuvolone M, Rampoldi L, Cenci S*, Milan E*. The Interaction of the Tumor Suppressor FAM46C with p62 and FNDC3 Proteins Integrates Protein and Secretory Homeostasis. Cell Rep. 2020;32(12):108162.
Lee FE, Wrammert J, Cenci S. Editorial: Advances in Plasma Cells in Health and Disease. Front Immunol. 2020;11:606737
Cavalli G and Cenci S. Autophagy and protein secretion. J Mol Biol. 2020;432(8):2525-2545.
Oliva L, Orfanelli U, Resnati M, Raimondi A, Orsi A, Milan E, Palladini G, Milani P, Cerruti F, Cascio P, Casarini S, Rognoni P, Touvier T, Marcatti M, Ciceri F, Mangiacavalli S, Corso A, Merlini G and Cenci S. The amyloidogenic light chain is a stressor that sensitizes plasma cells to proteasome inhibitor toxicity. Blood 2017;129(15):2132-2142.
Milan E, Perini T, Resnati M, Orfanelli U, Oliva L, Raimondi A, Cascio P, Bachi A, Marcatti M, Ciceri F and Cenci S. A plastic p62-dependent autophagic reserve maintains proteostasis and determines proteasome inhibitor susceptibility in multiple myeloma cells. Autophagy 2015;11(7):1161-1178.
Benasciutti E, Mariani E, Oliva L, Scolari M, Perilli E, Barras E, Milan E, Orfanelli U, Fazzalari NL, Campana L, Capobianco A, Otten L, Particelli F, Acha-Orbea H, Baruffaldi F, Faccio R, Sitia R, Reith W and Cenci S. MHC Class II Transactivator is an in vivo regulator of osteoclast differentiation and bone homeostasis co-opted from adaptive immunity. J Bone Min Res. 2014; 29(2):290-303.
Pengo N, Scolari M, Oliva L, Milan E, Mainoldi F, Raimondi A, Fagioli C, Merlini A, Mariani E, Pasqualetto E, Orfanelli U, Ponzoni M, Sitia R, Casola S and Cenci S. Plasma cells require autophagy for sustainable immunoglobulin production. Nat Immunol. 2013; 14(3):298-305.
Cenci S. The proteasome in terminal plasma cell differentiation. Semin Hematol. 2012; 49(3):215–222.
Cenci S, van Anken E, Sitia R. Proteostenosis and plasma cell pathophysiology. Curr Opin Cell Biol. 2011; 23(2):216-22.
Bianchi G, Oliva L, Cascio P, Pengo N, Fontana F, Cerruti F, Orsi A, Pasqualetto E, Mezghrani A, Calbi V, Palladini G, Giuliani N, Anderson KC, Sitia R and Cenci S. The proteasome load vs. capacity balance determines apoptoptic sensitivity of multiple myeloma cells to proteasome inhibition. Blood. 2009; 113:3040-3049.