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Myriam Gorospe , Ph.D., Chief
The mission of the RNA Regulation Section (RRS), led by Myriam Gorospe, is to investigate the post-transcriptional mechanisms that regulate gene expression programs across early and mid life, influencing aging traits. The Section is particularly interested in the control of mRNA processing, splicing, transport, turnover, and translation by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs). The working hypothesis in the RRS is that post-transcriptional gene regulation directly impacts upon the normal physiologic decline of aging and the aberrant gene expression programs that drive age-associated disease. The Section is testing this hypothesis in normal aging processes by analyzing the impact of RBPs and ncRNAs on age-associated inflammation, impaired muscle regeneration, cellular senescence, and declining responses to proliferative and metabolic stimuli. The Section is also testing this hypothesis in age-associated diseases by studying the impact of RBPs and ncRNAs on post-transcriptional gene regulation in pathologies of aging such as diabetes, obesity, sarcopenia, neurodegeneration, and cancer.
Portfolio/Research Areas
Using a range of cell models of aging-associated declines and diseases, the RRS studies the function of RBPs and ncRNAs in four main research areas:
• Cell senescence, including gene expression programs and function of senescent cells, and the senescence-associated secretory phenotype (SASP)
• Energy metabolism, focusing on organelles (mitochondria) and cells (pancreatic cells, muscle cells, and fat cells) that metabolize energy and become impaired in diabetes, obesity, and muscle function
• Cellular response to stress, with a focus on DNA damage, oxidative stress, and nutrient deprivation
• Mental health, through the analysis of gene expression programs and cell types implicated in processes that affect neuronal development, regeneration, and degeneration
Findings and Publications
Steri, M., Orrù, V., Idda, M.L., Pitzalis, M., Pala, M., Zara, I., Sidore, C., Faà, V., Floris, M., Deiana, M., Asunis, I., Porcu, E., Mulas, A., Piras, M.G., Lobina, M., Lai, S., Marongiu, M., Serra, V., Marongiu, M., Sole, G., Busonero, F., Maschio, A., Cusano, R., Cuccuru, G., Deidda, F., Poddie, F., Farina, G., Dei, M., Virdis, F., Olla, S., Satta, M.A., Pani, M., Delitala, A., Cocco, E., Frau, J., Coghe, G., Lorefice, L., Fenu, G., Ferrigno, P., Ban, M., Barizzone, N., Leone, M., Guerini, F.R., Piga, M., Firinu, D., Kockum, I., Lima Bomfim, I., Olsson, T., Alfredsson, L., Suarez, A., Carreira, P.E., Castillo-Palma, M.J., Marcus, J.H., Congia, M., Angius, A., Melis, M., Gonzalez, A., Alarcón Riquelme M.E., da Silva, B.M., Marchini, M., Danieli, M.G., Del Giacco, S., Mathieu, A., Pani, A., Montgomery, S.B., Rosati, G., Hillert, J., Sawcer, S., D'Alfonso, S., Todd, J.A., Novembre, J., Abecasis, G.R., Whalen, M.B., Marrosu, M.G., Meloni, A., Sanna, S., Gorospe, M., Schlessinger, D., Fiorillo, E., Zoledziewska, M., and Cucca, F.: Overexpression of the cytokine BAFF and autoimmunity risk . The New England Journal of Medicine 376: 1615-1626, 2017 (PMC5605835).
Zhang, P., Kishimoto, Y., Grammatikakis, I., Gottimukkala, K., Cutler, R.G., Zhang, S., Abdelmohsen, K., Bohr, V.A., Sen, J.M., Gorospe, M., and Mattson, M.P.: Senolytic therapy ameliorates Aβ-Associated cellular senescence, inflammation and cognitive deficits in an Alzheimer’s disease model. Nature Neuroscience 22: 719-728, 2019 (PMC6605052).
Orrù, V., Steri, M., Sidore, C., Marongiu, M., Serra, V., Olla, S., Sole, G., Lai, S., Dei, M., Mulas, A., Virdis, F., Piras, M.G., Lobina, M., Marongiu, M., Pitzalis, M., Deidda, F., Loizedda, A., Onano, S., Zoledziewska, M., Sawcer, S., Devoto, M., Gorospe, M., Abecasis, G.R., Floris, M., Pala, M., Schlessinger, D., Fiorillo, E., Cucca, F. Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat Genet. 2020 Oct;52(10):1036-1045. (PMC8517961).
Anerillas, C., Mazan-Mamczarz, K., Herman, A.B., Munk, R., Lam, K.G., Calvo-Rubio, M., Garrido, A., Tsitsipatis, D., Martindale, J.L., Altés, G., Rossi, M., Piao, Y., Fan, J., Cui, C.Y., De, S., Abdelmohsen, K., de Cabo, R., Gorospe. M.: The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress. Nat Aging. 2023 Oct;3(10):1237-1250. (PMC11369890).
Herman, A.B., Tsitsipatis, D., Anerillas, C., Mazan-Mamczarz, K., Carr, A.E., Gregg, J.M., Wang, M., Zhang, J., Michel, M., Henry-Smith, C.A., Harris, S.C., Munk, R., Martindale, J.L., Piao, Y., Fan, J., Mattison, J.A., De, S., Abdelmohsen, K., Maul, R.W., Tanaka, T., Moore, A.Z., DeMouth, M.E., Sidoli, S., Ferrucci, L., Liu, Y., de Cabo, R., Lakatta, E.G., Gorospe, M. DPP4 inhibition impairs senohemostasis to improve plaque stability in atherosclerotic mice. Journal of Clinical Investigation 133:e165933, 2023 (PMC10266795).