Regulation of iron metabolism
Laura Silvestri
Email: silvestri.laura@hsr.it
Location: DIBIT1 A3, Floor 4, Room 83
Project leader, Regulation of iron metabolism Unit
Adjunct professor, Vita-Salute San Raffaele University
After graduation in “Chimica e Tecnologia Farmaceutiche”, LS obtained her PhD in Biotechnology at the Università degli Studi di Milano, Italy. She carried out her post-doctoral training at the San Raffaele Scientific Institute in Milan, Italy in the “Molecular mechanisms in neurodegenerative disorders” Unit. Then she moved to the “Regulation of Iron Metabolism Unit” as senior post-doc and then as research associate since 2015. She was appointed as Project leader in 2016. She is actively involved in the following International Societies as the American Society of Hematology (Vice chair-Scientific Committee on Iron and Heme, ASH; 2022-2023) and the European Hematology Association (Committee member of the Scientific Working Group on Red cells and Iron, EHA; 2022-).
Non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver disorders in developed countries, is characterized by steatosis with hepatic inflammation and can progress to non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis and hepatocellular carcinoma. The metabolically active skeletal muscle is affected by NAFLD and can affect NAFLD development since low muscle mass and muscular atrophy are associated with a poor NAFLD prognosis. A close correlation between iron and lipid metabolism has been suggested.
The liver hormone hepcidin is a key regulator of iron homeostasis. At a systemic level, hepcidin, controlled by the BMP-SMAD pathway, regulates dietary absorption, storage and tissue distribution by blocking the function of the sole iron exporter ferroportin. Hepcidin regulation integrates multiple signals coming from the liver, bone marrow, blood, kidney and skeletal muscle.
Main research interests are:
- The characterization of the mechanism/s of hepcidin regulation in physiologic and pathologic conditions as Hereditary Hemochromatosis, Iron Refractory Iron Deficiency Anemia (IRIDA), beta thalassemia.
- The characterization of the crosstalk between liver and skeletal muscle in the regulation of NAFLD-NASH development, in collaboration with Paolo Porporato (UniTO) and the development of new therapeutic strategies aimed at upregulating the BMP-SMAD pathway both in liver and skeletal muscle to improve the outcome of this metabolic disorder.
- The pharmacologic targeting of the liver epigenetic components of NAFLD-NASH by using antisense oligonucleotides for phenotype amelioration (collaboration with Simona Pedrotti and Davide Gabellini.
Nai A, Lorè NI, Pagani A, De Lorenzo R, Di Modica S, Saliu F, Cirillo DM, Rovere-Querini P, Manfredi AA, Silvestri L. Hepcidin levels predict Covid-19 severity and mortality in a cohort of hospitalized Italian patients. Am J Hematol. 2021 Jan;96(1):E32-E35. doi: 10.1002/ajh.26027.
Pagani A., Pettinato M., Colucci S., Dulja A., Rauner M., Nai A., Camaschella C., Altamura S., Muckenthaler M., Silvestri L., Hemochromatosis proteins are dispensable for the acute hepcidin response to BMP2. Haematologica. 2020. doi: 10.3324/haematol.2019.241984.
Nai A., Pettinato M. Federico G., Carlomagno F. and Silvestri L. Tamoxifen erythroid toxicity revealed by studying the role of Nuclear Receptor Co-Activator 4 in erythropoisis. Haematologica. (2019). Haematologica. 2019 Aug;104(8):e383-e384. doi: 10.3324/haematol.2019.224857.
Artuso I, Pettinato M, Nai A, Pagani A, Sardo U, Billoré B, Lidonnici MR, Bennett C, Mandelli G, Pasricha SR, Ferrari G, Camaschella C, Kautz L, Silvestri L. Transient decrease of serum iron after acute erythropoietin treatment contributes to hepcidin inhibition by ERFE in mice. Haematologica. 2018 Sep 28. pii: haematol.2018.199810. doi: 10.3324/haematol.2018.199810.
Colucci S., Pagani A., Pettinato M., Artuso I., Nai A., Camaschella C., Silvestri L. The immunophilin FKBP12 inhibits hepcidin expression by binding the BMP type I receptor ALK2 in hepatocytes. (2017) Blood. 2017 doi: 10.1182/blood-2017-04-780692. Highlighted in Blood. Parrow NL, Fleming RE. Releasing the FKBP12 brake on hepcidin. Blood. 2017 Nov 9;130(19):2049-2050. doi: 10.1182/blood-2017-09-805390.
Pagani, A., Colucci, S., Bocciardi, R., Bertamino, M., Dufour, C., Ravazzolo, R., Silvestri, L.*, Camaschella, C*. A new form of IRIDA due to combined heterozygous mutations of TMPRSS6 and ACVR1A encoding the BMP receptor ALK2 (2017) Blood, 129 (25), pp. 3392-3395. DOI: 10.1182/blood-2017-03-773481 *: co-last authors
Nai, A., Rubio, A., Campanella, A., Gourbeyre, O., Artuso, I., Bordini, J., Gineste, A., Latour, C., Besson-Fournier, C., Lin, H.Y., Coppin, H., Roth, M.-P., Camaschella, C., Silvestri, L.*, Meynard, D*. Limiting hepatic Bmp-Smad signaling by matriptase-2 is required for erythropoietin-mediated Hepcidin suppression in mice (2016) Blood, 127 (19), pp. 2327-2336. *: co-last and co-corresponding authors Highlighted in Blood. Bartnikas T. Matriptase-2 links erythropoietin to iron. Blood 2016 127:2270-2271.
Complete List of Published Work in My Bibliography here