The research focus of Eduardo N. Chini, M.D., Ph.D., is in the fields of metabolism, nutrition, obesity, pharmacology, cancer and aging, and kidney disease. In particular, Dr. Chini is interested in nicotinamide adenine dinucleotide (NAD) metabolism and functions. He and his colleagues are exploring the nonoxidative and oxidative roles of NAD (as a signaling molecule and energy coin in cells). Dr. Chini's laboratory has done seminal work on NAD catabolism, including the description of the main enzyme responsible for the degradation of this molecule in mammalian tissues.

Focus areas

• SIRT1 function and regulation. The NAD-dependent deacetylase sirtuin-1 (SIRT1) is an enzyme that is involved in several signaling pathways. SIRT1 appears to be a master regulator of aging, metabolism and circadian cycle. SIRT1 has also been implicated as the target for the polyphenolic compound resveratrol and may be implicated in the physiological effects of caloric restriction.

  Dr. Chini's team has described for the first time a new crucial enzymatic system, the CD38 pathway, as the main regulator of intracellular NAD levels and SIRT1 activity in vivo. Current work is focusing on this pathway as a possible drug target for the treatment of obesity and metabolic diseases.

• DBC1 regulation of SIRT1. Dr. Chini and colleagues have described that the modulation of SIRT1 by the protein DBC1 is dynamic and is regulated by the metabolic load of the cell. They are now exploring the role of SIRT1-DBC1 interaction as a target for small molecule activators of the SIRT1 pathway and the effects of the interaction on the development of fatty liver (steatosis) in mice.
• NAD metabolism in cancer. The molecule NAD is a potential target for novel cancer therapy for several types of cancers, including the deadly pancreatic cancer.
• Polycystic kidney disease. Dr. Chini is investigating the role of metabolism and nutrition in polycystic kidney disease.

Significance to patient care

The ultimate goal of Dr. Chini's research is to provide new avenues for the development of novel and effective pharmacological therapeutic approaches for human diseases such as obesity, metabolic syndrome, aging-related disease and kidney disease, and their complications, such as autosomal dominant polycystic kidney disease (ADPKD) premature labor.