Obesity is a serious medical problem that involved a high percentage of the world population. Traditionally conceived as a disease of developed countries, it is now recognized as a pandemic by WHO. In Uruguay, nearly 60% of the adult population are considered overweight or obese. Moreover, about 10% of the child population is overweight or obese, and they suffer hypertension and diabetes, pathologies associated with obesity. Understanding the molecular mechanisms involved in pathophysiology of obesity, diabetes and other associated diseases is our main goal. Research aims on Metabolic Diseases and Aging Lab are:
a) to do basic science focused on the molecular mechanisms of metabolic diseases, with a strong emphasis on Sirtuins;
b) To develop novel pharmacological strategies to treat obesity and metabolic diseases.
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).
2014-2019 – Young leaders grant. INNOVA – ANII.
2017-2018 – Eolo Pharma: A pharmaceutical company for the development of new compounds for the treatment of metabolic and cardiovascular diseases. CITES-SANCOR. Co-responsible: Carlos Batthyany and Virginia López.
2017-2019 – New role of CD38 in the regulation of acute inflammatory response. R&D scholarship, CSIC. Co-responsible: Paola Contreras
2016-2018 – Agence universitaire de la Francophonie (AUF). Co-responsible: Marcelo Hill (Laboratory of Immunoregulation and Inflammation).
2015-2017 – Role of the DBC1 protein in the physiology of fat tissue during obesity. Clemente Estable Fund. ANII.
2015-2017 – Creation and development of NutraScan – ANII. Alliance Pasteur-Granuy. Co-responsible: Carlos Batthyany.
“Treatment methods of conditions related to inflammation using pluripotent anti-inflammatory and metabolic modulators”. Inventors: Batthyany, C., Lopez, G.V., Escande, C., Porcal, W., Dapueto, R., Rodriguez, R., Galliussi, G., and Garat, M.P. 2016. Provisional patent application in the United States; to be assigned // on hold.
“Derivatives of trolox and methods of use in the treatment and prevention of conditions related to inflammation”. Inventors: Batthyany, C., Lopez, G.V., Dapueto, R., Escande, C., and Rodriguez, R. 2016. Non-provisional patent application in the United States; to be assigned // on hold.