Ángela M. Valverde
Angela M Valverde PhD has been linked to the university from 1987. She has been in teaching of different PhD programs in biochemistry, molecular biology, cell-biology and biomedicine areas. She is actually associated Professor at Universidad Complutense de Madrid and is involved in the Master of Molecular Biomedicine at Universidad Autónoma de Madrid. She has supervised 10 PhD students, 3 of whom are still ongoing, 4 Master students, 5 graduate students, as well as 5 technicians. All previous PhD students have followed scientific careers and are currently working in either academia (Spanish Scientific Council, Spanish National Center of Oncology Research) or Pharmaceutical Industry (Lilly S.A.). Dr. Valverde is Principal Investigator at IIBm Alberto Sols (CSIC/UAM) and belongs to CIBERdem (Spanish network for the study of diabetes and associated metabolic disorders) with the following research lines.
1. Group description
Molecular mechanisms of insulin resistance, insulin sensitivity, islet development and diabetic complications.
2. Research lines
- Study of the molecular mechanisms associated to the progression of non-alcoholic fatty liver disease (NAFLD):
- Dual role of the protein tyrosine phosphatase 1B (PTP1B) in NAFLD: from intestinal inflammation to hepatic fibrosis.
- Cross-talk between different liver cells (hepatocytes, Kuffer cells, stellate cells) in the context of NAFLD progression: molecular mechanisms involved.
- Differential effects of single and dual agonists of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) in the treatment of NAFLD at stages of non-alcoholic steatohepatitis (NASH).
- Role of insulin receptor substrate 2 (IRS2) in the epithelial-mesenchymal transition (EMT) in hepatic cells in insulin resistant states.
- Differential therapeutic effects of single and dual agonists of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) in the treatment of insulin resistance associated to obesity: effects of these drugs in the liver and brown adipose tissue.
- Effect of low grade chronic inflammation on insulin and catecholamine sensitivity in brown adipocytes: molecular mechanisms involved and therapeutic strategies.
- Study of the polarization of microglia (M1/M2) in diabetic retinopathy (DR): targeting microglia polarization as a therapeutic approach at the early stages of DR.
- Involvement of Tyrosine Hydroxilase in the metabolic adaptations to diet and temperature stressors.
- Molecular mechanisms of insulin resistance/sensitivity in brown adipocytes
3. TREATMENT project
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ESR1
ESR1 will analyze tissue-specificity of schizophrenia and antipsychotic drugs on insulin sensitivity in order to unravel the tissue specificity of the critical nodes of insulin signalling that are dysregulated by the schizophrenia per se or as a consequence of the impact of the pharmacological treatment with olanzapine/aripriprazol catabolism on whole body metabolic control. The ESR will examine the selective modulation of the critical nodes of insulin signalling (IR, IRS1/2, PTP1B, Akt) during schizophrenia per se and under antipsychotic therapy and the impact on whole body glucose homeostasis and energy expenditure. We expect to find differences in insulin-sensitive cells and tissues from mice treated with drugs for short or long time-periods. Secondly, the ESR will conduct studies in genetically modified (GM) mice bearing tissue-specific insulin resistance (IRS2 KO) or hypersensitivity (PTP1B KO). This approach will be relevant for the design of combined therapies aimed to ameliorate metabolic disturbances linked to antipsychotic treatments.
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ESR2
ESR2 will study the effect of antipsychotic drugs in the pancreas in order to analyze the impact of schizophrenia per se and its pharmacological treatment with olanzapine or aripiprazol in the molecular machinery that modulates the endocrine pancreas. The ESR will study the effects of schizophrenia per se and its treatment with antipsychotic drugs in the endocrine pancreas. By using cellular models of pancreatic alpha and beta cells, we expect to unravel alterations in the molecular mechanisms of insulin/glucagon secretion and cell plasticity due to antipsychotic drugs. It is expected to find altered responses to gastrointestinal peptides, particularly GLP1R agonists. In the in vivo mouse models of schizophrenia or its pharmacological treatments, the ESR will analyse if and how islet morphometry may be altered together with increased ER stress (PERK, ATF6, IRE1α) and apoptosis (Bax/Bak, caspase-3), limiting the first and second phase of insulin secretion.
4. Current funded projects
- “Identification of novel modulators of chronic inflammation in prevalent diseases: unveiling divergent mechanisms of disease”. INFLAMES. PIE14/00045, (ISCIII, Spain). Coordinator: Antonio Zorzano Olarte Principal Investigator of WP3: Ángela M. Valverde. From 01/01/2015 to 12/31/2017.
- “Inflammation associated with chronic metabolic damage in Type 2 diabetes and its complications. SAF 2015-65.267 RETOS (2016-2018) (MINECO/FEDER). Principal Investigator: Ángela M. Valverde. From 01/01/2016 to 12/31/2018.
- RESEARCH NETWORK IN NRF2 AS A NODE OF PATHOGENOSOME. SAF2015-71304-REDT (2016-2017) MINECO. Coordinator: Antonio Cuadro Pastor. Principal Investigator: Ángela M. Valverde. From 01/01/2015 to 31/12/2017.
- Since 2008 Angela M. Valverde participates as PI in CIBERdem Network for the study of diabetes and metabolic diseases, Instituto de Salud Carlos III, Madrid (Spain).
5. Group members
- Irma García Martinez: Postdoctoral researcher funded by Juan de la Cierva Program (MINECO (Spain)
- Patricia Rada Llano: Postdoctoral researcher funded by Juan de la Cierva Program (MINECO (Spain)
- Pilar Valdecantos: Postdoctoral researcher funded by CIBERdem consortium (ISCIII, Spain)
- Patricia Vázquez Pérez: Postdoctoral researcher funded by CIBERdem consortium (ISCIII, Spain)
- Ines Barahona: PhD student funded by MINECO (Spain)
- Carmen Escalona Garrido: PhD student funded by MECD (Spain)
- Carmen Rubio Caballero: PhD student funded by MECD (Spain)
- Andrea Villar Lorenzo: PhD Student funded by MINECO (Spain)
- María de los Ángeles Ramos: Technical Staff funded by CSIC.
