- Licenciado in Biochemistry, Universidad Austral de Chile, Chile, 1990
- Biochemist, Universidad Austral de Chile. Chile, 1990
- Research Associate, School of Biological Sciences, University of Missouri-Kansas City, USA, (1993 - 1995).
- Ph.D., Cell and Molecular Biology, Universidad Austral de Chile, Chile, 1997.
The main aim of our laboratory is to investigate control mechanisms of gluconeogenesis under normal and pathological conditions. To achieve this, we have focused on the study of FBPase, a key regulatory enzyme of this metabolic pathway, and the relation of this enzyme with other gluconeogenic and glycolytic enzymes, including those indirectly involved in glycogen synthesis. Thus, one of our main objectives has been to localize FBPase in different human and rat tissues, to further understand its function in a cellular context. However, contrary to that expected, we have proven that FBPase is widely distributed, with the enzyme found in various non-gluconeogenic tissues. And expression of this enzyme is linked to aldolase isoenzymes, specifically aldolase B, with which it forms a multienzyme complex. We have also managed to show that, in kidney, compartmentalization of metabolic pathways in different nephon cells is one mechanism by which metabolism is controlled.
Through other studies, we have been able to show that intracellular localization of these FBPases and aldolase B is dynamic, and is modulated by the action of specific metabolites and hormones. This finding has led us to propose this phenomenon as a new mechanism of regulation of both gluconeogenic and glyconeogenic pathways. Nuclear localization of FBPase and aldolases and their probable function in this important compartment is one of the key aspects of our research.
One of the major pathologies associated with metabolic disorder is Diabetes mellitus, characterized by chronic hyperglycaemia that arises from an upset in carbohydrate, lipid and protein metabolism. Chronic diabetes produces renal damage, with diabetic nephropathy (ND) being one of the most devastating renal diseases known, with a high number of patients requiring renal substitution therapy. In diabetic humans, we found that there is a 300% increase in endogenous glucose production in kidney, compared to a 30% hepatic increase. We propose that this elevated increase at kidney level might be responsible for the glycogen stimulation and accumulation commonly observed in diabetic nephropathies, and that gluconeogenesis increase and glycogen synthesis are integrated.
We are also very interested in diagnosis of diabetic nephropathy. Current diagnosis is by detection of albumin excretion in urine (microalbuminuria). But this parameter, shown to be unspecific in confirming progression of diabetic nephropathy, involves renal biopsies, a controversial invasive procedure. Thus, using biotechnology techniques, we are identifying and analyzing new biomarkers specific for early stage ND (glomerular dysfunction) and for advanced stages of the disease (tubular dysfunction).
- Alejandro J. Yáñez, Ximena Bustamante, Romina Bertinat, Enrique Werner, Maria Cecilia Rauch, Ilona I. Concha, Juan G Reyes and Juan C. Slebe. “Expression of key substrate cycle enzymes in rat spermatogenic cells: fructose 1,6 bisphosphatase and 6 phosphofructose 1-kinase”. Journal of cellular Physiology, EN PRENSA .
- Alejandro J. Yáñez, Romina Bertinat, Carlos Spichiger, Juan G. Carcamo, María de los Angeles García, Ilona I. Concha, Francisco Nualart and Juan C. Slebe (2005). “Novel expression of liver FBPase in Langerhans islets of human and rat pancreas”. Journal of Cellular Physiology. 205(1):19-24.
- Alejandro J. Yañez, Heide C. Ludwig, Romina Bertinat, Carlos Spichiger, Rodrigo Gatica, Gustavo Berlien, Oscar Leon, Monica Brito, Ilona I. Concha and Juan C. Slebe (2005). “Different involvement for aldolase isoenzymes in kidney glucose metabolism. Aldolase B but not aldolase A colocalizes and form a complex with FBPase”. Journal of Cellular Physiology 202(3): 743 – 753.
- Alejandro J. Yáñez, Mar Garcia-Rocha, Romina Bertinat, Cristian Droppelman, Ilona I. Concha, Joan J. Guinovart and Juan C. Slebe.(2004) “Subcellular localization of liver FBPase is modulated by metabolic conditions”. FEBS Letters, 577(1-2): 154-158.
- Alejandro J. Yáñez, Romina Bertinat, Ilona I. Concha, and Juan C. Slebe (2003). Nuclear localization of liver FBPase isoenzyme in kidney and liver. FEBS Letters. 550 (1-3): 35-40.
- Alejandro J. Yánez, Francisco Nualart, Cristian Droppelmann, Romina Bertinat, Mónica Brito, Ilona I. Concha, and Juan C. Slebe. (2003). “Broad expression of fructose-1,6-bisphosphatase and Phosphoenolpyruvate carboxykinase provide evidence for gluconeogenesis in human tissues other than liver and kidney”. Journal of Cellular Physiology, 197: 189-197.