Genetics and epigenetics in human disease

Both genetic and epigenetic changes contribute to development of human disease. ER’s laboratory has a proven experience in different research areas: screening of patients with mental retardation/multiple congenital anomalies syndromes, through the use of fluorescent in situ hybridization and array-CGH analysis, and identification of causative genomic rearrangements; application of array-CGH in solid tumors in order to identify molecular alterations prognostically and pathogenetically informative; screening of infertile men to define X-linked genetic factors involved in male sterility; application of array-CGH in Sry-negative XX sex reversal dogs in order to clarify the complicated network of genes and hormones driving sex determination in mammals.

More recently, the activity of the laboratory also focuses on the analysis of epigenetic regulatory pathways in diffuse fibrotic lung disorders and rare pleural malignancies. Specifically, the current work is to establish the role of miRNAs in these lung diseases through the use of in situ hybridization analysis on paraffin embedded human and rat lung tissue samples and on mesenchimal cells.  An increasing number of studies have demonstrated that miRNAs play a critical role in the pathogenesis of a variety of diseases, including cancer, inflammation and fibrosis in the heart, liver, kidney, and lung. The identification of candidate dysregulated miRNAs will highlight key epigenetic regulators of lung disease which may represent new therapeutic targets in specific phenotypes of patients.

 

 Selected Papers

 

Correlation between genomic alterations assessed by array comparative genomic hybridization, prognostically informative histologic subtype, stage, and patient survival in gastric cancer. Rossi E, Klersy C, Manca R, Zuffardi O, Solcia E. Hum Pathol. 2011 Dec;42(12):1937-45. doi: 10.1016/j.humpath.2011.02.016. Epub 2011 Jun 14.

De novo unbalanced translocations in Prader-Willi and Angelman syndrome might be the reciprocal product of inv dup(15)s. Rossi E, Giorda R, Bonaglia MC, Candia SD, Grechi E, Franzese A, Soli F, Rivieri F, Patricelli MG, Saccilotto D, Bonfante A, Giglio S, Beri S, Rocchi M, Zuffardi O.PLoS One. 2012;7(6):e39180. doi: 10.1371/journal.pone.0039180. Epub 2012 Jun 14.

Sox9 duplications are a relevant cause of Sry-negative XX sex reversal dogs. Rossi E, Radi O, De Lorenzi L, Vetro A, Groppetti D, Bigliardi E, Luvoni GC, Rota A, Camerino G, Zuffardi O, Parma P. PLoS One. 2014 Jul 10;9(7):e101244. doi: 10.1371/journal.pone.0101244. ECollection 2014.