IUIBS: Molecular and Translational Pharmacology

Affiliated Research areas

• Immune-related diseases
• Prevention, Diagnosis and Treatment of Human Diseases
• Pharmacology and toxicology
• Strategy, operation research

Scientific Areas

• Not available

Keywords

• Antitumoral drugs
• Multikinase modulators
• Nuclear Receptor-Cytokine
• Drug repurposing
• Immuneinflamation
• Química Médica
• Drug Discovery
• Sarcomas
• Statins
• Drug repurposing
• Pharmacogenomic
• Differential gene expression
• Functional Genomic
• SERM
• SERD

Summary

- Bioassays in cellular models and animals of human diseases: Phenotypic screening laboratory or based on molecular targets (nuclear receptors, kinases, transcription factors). Real-time analysis of the efficacy and toxicity of newly synthesized small molecules or repositioned drugs in rare diseases. 2D, 3D or organoid cell models. Kinetics and dose-response studies, in real time on: cell proliferation, cytotoxicity, apoptosis, migration, invasion, mitochondrial metabolism, angiogenesis, reporter genes. protein phosphorylation. High throughput analysis system, Incucyte SX5 (up to 6 96-well plates, simultaneously) of 2D, 3D or organoid cell phenotypes. Models of human diseases in genetically modified mice: functional role of SOCS2 in metabolic diseases (Type II Diabetes, Gestational Diabetes, disorders of gluconeogenesis and lipogenesis) or liver cancer. Non-genetically modified rodent models of NASH, Diabetes, Osteoporosis, Atherosclerosis, Hepatocarcinoma.
- R&D in pharmacology applied to oncology: Identification of new small molecules with biomedical interest in Oncology. Drug discovery. Preclinical pharmacological and toxicological evaluation. Translational pharmacology and company.
- Citocins and diabetic foot - Pathology of the thyroid gland - experimental hepatocarcinoma: Identification of immunological and genetic biomarkers associated with diabetic foot. Application of biochemical and genetic techniques in the characterization of the healing process of the diabetic foot. Thyroid Pathology. Hepatocellular carcinoma.
- Pharmacokinetics Biodisponability studies. ADMET PREDICTION: Pharmacokinetic and bioavailability. ADMET. Determination of drugs and metabolites in biological samples. Development of drug-carrying nanoparticles.
- Drug Repurposing in Orphan Diseases: Drug repurposing in rare diseases. Repositioning statins in the treatment of sarcomas and blood cancer. Drug repurposing aims to find existing EU or FDA-approved drugs for diseases. The basic idea of drug repurposing is to discover new useful activity for a distinct disease in an older clinically used drug or one that failed in later stages of development or disease develop resistance to drug. Our lab follow a drug repositioning strategy to identify advanced uses for statins (hipolipidemic drugs) and sarcomas.
- Pharmacogenomics applied to the discovery and development of drugs. Microarrays DNA (Agilent Platform) Bioinformatics: The IUIBS Genomics laboratory has an Agilent platform for the analysis of DNA microarrays that is offered to the scientific community of our academic and business environment. Pharmaco-Toxicogenomics, defined as the dynamic study of the transcriptome and its regulatory elements applied to the discovery of the mechanism of action and toxicity of drugs. In our laboratory we have a Functional Genomics Unit to address the study of gene expression, on a large scale, in temporal or dose-dependent models. This has allowed the creation of extensive databases that are being used to decipher signaling pathways and identify new biomarkers and drug targets. The biomarkers that emerge from these studies may have prognostic value and can be used to predict therapeutic outcomes and drug toxicity. This methodological approach is proving to be very useful for shortening the R+D+i+t time of a drug, facilitating the identification of more potent and less toxic drug combinations.
- Metabolism and socs: The Suppressor of Cytokine Signaling (SOCS)-2 is a critical regulator of somatotropic-liver axis, gluconeogenesis and hyperglycemia and lipid metabolism by modulating the GHR-Janus Kinase 2 (JAK2)-Signal Transducer and Activator of Transcription (STAT)- 5b signaling pathway. In addition, SOCS2 modulates immune-inflammatory-response, hepatocyte proliferation and repair and hepatocarcinogenesis. This is clinically relevant because SOCS2 expression has been linked to gigantism, diabetes, liver steatosis, immune-inflammatory-related diseases, and liver cancer. Elucidate how SOCS2 deletion impacts on cytokine liver transcriptome as well as on metabolism (glucose and lipid metabolism), immune system response (the biology of macrophages) and liver cancer is a main aim of our Research Group
- Pharmacodynamics Bioensayos for the identification of antitumor-inhibitor compounds: The STAT (Signal Transducer and Activator of Transcription) family proteins are essential for regulating the expression of genes necessary for cell growth and metabolism at all stages of development in mammals. In contrast, aberrant activation of STAT proteins results in the development of tumors, immunological and metabolic diseases. This justifies that these proteins are important pharmacological targets and that the identification of modulators (inhibitors or activators) of their biological activities is demanded. The objective that we pursue in this project is the discovery and development of new anti-STAT (1, 3, 5) molecules with potential antitumor and/or immunomodulatory activity. For this, we are carrying out the pharmacological evaluation of a chemical library (chemical library) that has been designed for the identification of inhibitors of the Jak/Stat proteins. This is done through a highly efficient approach based on the use of privileged structures from natural sources or through effective synthetic strategies, 3D-QSAR modeling studies and Docking. This strategy has been extensively validated for its effectiveness in discovering more selective, potent, and less toxic drugs. The ability of these products to modify STAT-dependent transcriptional activities is first assessed using cell lines transfected with luciferase reporter systems. Using these strategies, our laboratory has identified new drugs that inhibit the growth of human cancer cells dependent on the STAT pathway. In parallel, this project evaluates the most active molecules in relation to specific biological responses such as proliferation, apoptosis, migration, cell invasion, inflammatory response, or formation of tumor colonies. We apply high-resolution pharmaco-toxicogenomic strategies to accurately characterize the molecular mechanisms of new drugs. These studies are complemented by toxicological, antitumor or anti-inflammatory evaluation in in vivo animal models.
- Pharmacodynamics Bioassays for the identification of activities modulating nuclear receptors in the context of metabolic diseases and cancer: Our laboratory has specialized in procedures for the identification of new modulators of nuclear receptor activities (ER, GR, AR, LXR). These are done through a highly efficient chemical approaches based on the use of privileged structures from natural sources or through effective synthetic strategies, 3D-QSAR modeling studies and Docking. These strategies have been extensively validated for their effectiveness in discovering agonists, antagonists, or mixed agonists/antagonists, and their applications in metabolic diseases or cancer related to nuclear receptors. Preclinical phenotyping in cell and animal models. Using these strategies, our laboratory has identified numerous small molecules with agonist and/or antagonist activities of Estrogen Receptors with potential interest in Diabetes, hepatic steatosis, immunoinflammatory diseases or hormone-dependent cancer. We apply pharmaco-toxicogenomic strategies in a disease-based model to characterize the mechanism of action and predict the toxicity of new products before defining their efficacy and/or toxicity in vivo.