Dr. Pasquale Piccolo

miRNAs as biomarkers for AATD-related liver disease

A1AT deficiency (AATD) is a frequent genetic cause of liver disease and affects patients carrying the Z allele of A1AT (ATZ). The spectrum of liver disease includes hepatic failure to chronic hepatitis and increased risk of hepatocellular carcinoma. It is currently not possible to predict if a patient will develop the liver disease. Moreover, evaluation of disease progression or treatment efficacy can only rely on invasive procedures, (i.e.: liver biopsies)1. Therefore, new biomarkers are highly needed for AATD liver disease. MicroRNAs (miRNAs) have been proposed as biomarkers for several diseases. I performed miRNA-seq analysis in livers of PiZ mice, a transgenic mouse model expressing human ATZ and recapitulates the human hepatic disease. I identified a set of 104 miRNAs with significant up- or down-regulation compared to controls. Among these, miR-34b/c cluster was the most up-regulated.

Aim:

The main goal of my proposal is to identify miRNAs as biomarkers of liver disease due to AATD.

Specific aim 1 is to investigate the expression of selected miRNA in PiZ mice and then in sera of AATD patients.

Specific aim 2 is to investigate the role of miR-34b/c in the pathogenesis of the hepatic disease.

Novel miRNA biomarkers can be used for staging disease severity and to evaluate the therapeutic efficacy thus resulting in a major improvement in diagnosis and prognosis of AATD. Moreover, understanding the role of miRNAs with altered expression in AAT deficiency might provide new players involved in the disease pathogenesis and potentially novel drug targets.

Curriculum Vitae Dr. Pasquale Piccolo

Pasquale graduated with honors in Medical Biotechnology at the "Federico II" University of Naples, Italy. During his Ph.D. he started working on inherited metabolic disorders. By the end of his Ph.D., he moved to Baylor College of Medicine, Houston, TX were he get trained in gene therapy and helper-dependent adenoviral (HDAd) vector.

He currently works as post-doctoral associate  on gene therapy of inborn errors of liver metabolism at the Telethon Institute of Genetics and Medicine of Naples, Italy

His project "miRNAs as biomarkers for AATD-related liver disease" aims to support understanding the role of miRNAs with altered expression in AATD, providing new players involved in the disease pathogenesis and potentially novel drug targets.

Contact
Dr. Pasquale Piccolo
Telethon Institute of Genetics and Medicine (TIGEM)
Via Campi Flegrei 34, Pozzuoli
Naples - Italy