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RNA Regulation Section

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 in aging physiology and pathology. 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 as well as 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 investigating this hypothesis in age-associated diseases by testing 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 neurons) that store, sense, mobilize, create, and use energy

•  Cellular response to stress, with a focus on DNA damage, oxidative stress, and nutrient deprivation

•  Neurodegeneration, through the analysis of gene expression programs and cell types implicated in neurodegenerative processes

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).

Kim, K.M., Noh, J.H., Bodogai, M., Martindale, J.L., Yang, X., Indig, F.E., Basu, S.K., Ohnuma, K., Morimoto, C., Johnson, P.F., Biragyn, A., Abdelmohsen, K., and Gorospe, M.:: Identification of senescent-cell surface targetable protein DPP4. Genes & Development 31: 1529-1534, 2017 (PMC5630018).

Kim, K.M., Noh, J.H., Bodogai, M., Martindale, J.L., Pandey, P.R., Yang, X., Biragyn, A., Abdelmohsen, K., and Gorospe, M.: SCAMP4 enhances the senescent cell secretome. Genes & Development 32: 909-914, 2018 (PMC6075036).

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).

Pandey, P.R., Yang, J.H., Tsitsipatis, D., Panda, A.C., Noh, J.H., Kim, K.M., Munk, R., Nicholson, T., Hanniford, D., Argibay, D., Yang, X., Martindale, J.L., Chang, M.W., Jones, S.W., Hernando, E., Sen, P., De, S., Abdelmohsen, K., and Gorospe, M.: circSamd4 represses myogenic transcriptional activity of PUR proteins. Nucleic Acids Research 48: 3789-3805, 2020 (PMC7144931).

Recent Publications at PubMed

Myriam Gorospe, Ph.D.

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