Dr. Giuseppe Manco- IBBC – Institute of Biochemistry and Cell Biology - CNR
Abstract
Human paraoxonase 2 (PON2) is a lactonase that contributes to cellular defense and redox homeostasis. It hydrolyzes 3-oxo-dodecanoyl-homoserine lactone, a bacterial quorum-sensing molecule that regulates virulence factors. In addition, PON2 exhibits anti-ROS activity and protects against lipid peroxidation.
PON2 is implicated in several diseases characterized by excessive reactive oxygen species (ROS), including cancer. In this talk, I will report on novel post-translational modifications (PTMs) of PON2 to establish a link between redox conditions, lactonase activity, and stability.
Through in vitro and in vivo studies, we demonstrate that PON2 plays a crucial role in promoting wound healing under infected conditions. Based on these findings, we propose a working model that integrates redox regulation, enzymatic activity, and stability control of PON2.
Bio.
Dr. Giuseppe Manco is Research Director at the Institute of Protein Biochemistry (IBP-CNR), Naples. He graduated with honors in Biological Sciences from the University of Naples Federico II in 1987 and pursued fellowships at the International Institute of Genetics and Biophysics (1989–1991) and IBP-CNR (1992–1994). In 1995, he was a visiting researcher at the National Institutes of Health (Bethesda, USA) in the laboratory of Earl Stadtman and Rodney Levine. He became a permanent staff researcher at IBP-CNR in 1997, Senior Staff Researcher in 2001, and Research Director in 2020. He won and still holds the National Scientific Habilitations as Full Professor (ASN) in Biochemistry and Molecular Biology. He was nominated by SIB in 2019 as Italian Delegate of INPEC (International Network of Protein Engineering Centers). His H index on Google Scholar is 37 with more than 120 published papers.
Dr. Manco’s research explores structure–function relationships in enzymes, focusing on determinants of thermal stability, substrate recognition, inhibition, and catalysis. His work emphasizes enzymes from (hyper)thermophilic microorganisms, compared with mesophilic counterparts, to trace evolutionary hallmarks and promiscuous activities. He also investigates their potential applications in industry, environmental biotechnology, and human health. More recently, his studies have expanded to human proteins such as PON2 and the pyruvate dehydrogenase complex, with implications for cancer, diabetes, atherosclerosis, and nephropathies.
He is recognized for his contributions to the hormone-sensitive lipase (HSL) family and for co-discovering the phosphotriesterase-like lactonase (PLL) family with Dan Tawfik (Weizmann Institute). He coordinated many projects among which the “Biodefensor” project (PON_RIC 2007-2013) of 5 million euro. Ongoing projects are a PNRR INFACT subproject and a PRIN 2022 project.
