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Emanuela Tolosano
Associate Professor

Contacts
E-mail: emanuela.tolosano@unito.it
Office: 0116706423 Fax: 0116706432
Department of Molecular Biotechnology and Health Sciences

Research is focused on heme/iron metabolism. We are interested in mechanisms regulating heme trafficking between cells and tissues. The role of the plasma hemoglobin and heme scavengers, haptoglobin and hemopexin, respectively,  in physiologic and pathologic conditions is studied. The impact of heme export in heme/iron metabolism is addressed, by studying Flvcr (Feline Leukemia Virus subgroup C Receptor)1, that encodes for two heme exporters, Flvcr1a and Flvcr1b, located at the plasma membrane and in mitochondria, respectively.

We are interested in pathologic conditions associated to alterations of heme handling, like hemolytic disorders (sickle cell anaemia, thalassemia) and erythropoietic disorders. Finally, we are involved in the study of genetic diseases associated to mutations in Flvcr1 gene.

Here are our projects in detail:

  1. role of hemopexin in cardiovascular system;
  2. Evaluation of the efficacy of a haptoglobin- and/or hemopexin-based therapy to prevent/treat vasculopathy in sickle cell disease;
  3. role of Flvcr1 isoforms in erythropoiesis. Evaluation of Flvcr1-regulated intracellular heme pool in the control of expansion and differentiation of erytroid progenitors;
  4. role of Flvcr1 isoforms in endothelial cells and in vascular system;
  5. molecular characterization of Flvcr1 mutations found in patients suffering from neurological disorders.

  1. Morello N., Bianchi F.T., Marmiroli P., Tonoli E., Rodriguez Menendez V., Silengo L., Cavaletti G., Vercelli A., Altruda F. and Tolosano E., "A Role for Hemopexin in Oligodendrocyte Differentiation and Myelin Formation”, PlosOne, 6(5): e20173 (2011). 
  1. Fiorito V., Geninatti Crich S., Silengo L., Altruda F., Aime S. and Tolosano E., “Assessment of iron  absorption in mice by ICP-MS measurements of 57Fe levels”, Eur. J. Nutr.,  DOI: 10.1007/s00394-011-0256-6 (2011).
  1. Chiabrando D., Fiorito V., Marro S., Silengo L., Altruda F. and Tolosano E., “Cell-specific regulation of Ferroportin transcription following experimentally-induced acute anemia in mice”, Blood Cells Mol. Diseases, http://dx.doi.org/10.1016/j.bcmd.2012.08.002 (2012).
  1. Chiabrando D., Marro S., Mercurio S., Giorgi C., Petrillo S., Vinchi F., Fiorito V., Fagoonee S., Camporeale A., Turco E., Merlo G.R., Silengo L., Altruda F., Pinton P., Tolosano E., “The mitochondrial heme exporter FLVCR1b mediates erythroid differentiation”, Journal of Clinical Investigation 122(12):4569-79 (2012). doi: 10.1172/JCI62422. Epub 2012 Nov 26.
  1. Vinchi F., De Franceschi L., Ghigo A., Townes T., Cimino J., Silengo L., Hirsch E., Altruda F., Tolosano E., “Hemopexin Therapy Improves Cardiovascular Function by Preventing Heme-Induced Endothelial Toxicity in Mouse Models of Hemolytic Diseases”, Circulation 127(12):1317-29 (2013). Epub 2013 Feb 27. doi: 10.1161/​CIRCULATIONAHA.112.130179 (2013).
  1. Vinchi F. and Tolosano E., “Therapeutic approaches to limit hemolysis-driven endothelial dysfunction: scavenging free heme to preserve vasculature homeostasis”,Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 396527, 11 pages, (2013). doi:10.1155/2013/396527.
  1. Fiorito V., Geninatti Crich S., Silengo L., Aime S., Altruda F. and Tolosano E., “Lack of plasma protein Hemopexin results in increased duodenal iron uptake”, Plos One 8(6):e68146 (2013). 
  1. Rolla S., Ingoglia G., Bardina V., Silengo L., Altruda F., Novelli F.and Tolosano E., “THE ACUTE-PHASE PROTEIN HEMOPEXIN IS A NEGATIVE REGULATOR OF TH17 RESPONSE AND EXPERIMENTAL AUTOIMMUNE ENCEPHALOMIELITIS DEVELOPMENT” Journal of Immunology 191(11):5451-9 (2013)
  1. Vinchi F., Ingoglia G., Chiabrando D., Mercurio S., Turco E., Silengo L., Altruda F., Tolosano E., “Heme Exporter FLVCR1a Regulates Heme Synthesis and Degradation and Controls Activity of Cytochromes P450”, Gastroenterology 146: 1325–1338. doi: 10.1053/j.gastro.2014.01.053. [Epub ahead of print] (2014)
  1. Fiorito V., Neri F., Pala V., Silengo L., Oliviero S., Altruda F., Tolosano E., “Hypoxia controls Flvcr1 gene expression in Caco2 cells through HIF2α and ETS1”, BBA - Gene Regulatory Mechanisms 1839(4): 259-264 (2014). doi: 10.1016/j.bbagrm.2014.02.010
  1. Chiabrando D., Vinchi F., Fiorito V., Mercurio S. and Tolosano E., “Heme in pathophysiology: a matter of scavenging, metabolism and trafficking across cell membranes”, Front.Pharmacol. 8;5:61. eCollection 2014. doi:10.3389/fphar.2014.00061 (2014)
  1. Chiabrando D, Mercurio S, Tolosano E., “Heme and erythropoieis: more than a structural role”, Haematologica 99(6):973-983 (2014)

Research Products of Tolosano Emanuela

 

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