Metabolic Diseases and Aging

Research lines

DBC1 as modulator of metabolic function.
The main focus of our research has been to continue to understand the role of the protein Deleted in Breast Cancer-1 (DBC1), a SIRT1 regulator, in the control of metabolism and metabolic diseases. In order to achieve that, we took four different scientific approaches.

A) We continued using the genetic deletion of DBC1 mouse model
as an experimental paradigm in metabolism regulation;
B) we engaged in studying how DBC1 function is regulated in vivo. C) We decided to generate a loxp/loxp DBC1 mouse model as a tool for tissue-specific knockout of DBC1. D) Based on our previous data that DBC1 regulates the “healthy obesity” phenotype, we began to search for secreted targets of DBC1 that may account for its effects.

Novel regulators of metabolism and metabolic diseases
: focus on Inflammation. Chronic inflammation has emerged in the past few years as a major player in the development of metabolic diseases, with accumulating evidences showing that both innate and adaptive immune cells are involved in the onset and progression of obesity, type II diabetes and atherosclerosis. During this period, we begun to work with two different proteins in context of chronic inflammation and metabolic diseases: SIRT6 and “TMEM176B. Research and development in anti-obesity drugs.

The development of novel compounds for pharmacological treatment
of metabolic diseases was a seminal part of our G5 proposal. We associated in close collaboration with Dr. Carlos Batthyany, who together with Dr. Virginia Lopez had already designed several compounds aimed to treat atherosclerosis. Together, we showed that these compounds are effective in vivo for atherosclerosis. In the course of this scientific collaboration, we designed together a novel family of compounds, one of which is showing striking results on prevention of obesity, insulin resistance and non-alcoholic liver steatohepatitis (NASH).