MP17-Intercellular Communication
Precision Medicine / IBS-MP17 / Consolidated

The Research Group CTS-101: Intercellular Communication, consolidated by the Junta de Andalucía, is directed by Profs. Darío Acuña Castroviejo and Germaine Escames, Professors of Physiology at the University of Granada. It is made up of doctors Luis Carlos López, Associate Professor; Iryna Rusanova, Prof. Assistant Doctor; Ana López Ramírez and Elena Díaz Casado, Postdoctoral contractors, as well as 5 FPU and predoctoral fellows up to a number of 15 members. Darío Acuña Castroviejo is also a Clinical Analysis Specialist at the San Cecilio University Hospital, Scientific Advisor to the University's Scientific Instrumentation Center, and Supervisor of the Radioactive Facilities Laboratory of the Biomedical Research Center. He has been director of the ISCIII Thematic Network on the Molecular and Cellular Bases of Oxidative Damage in Aging between 2003-2006, which in 2016 became the CIBER of Aging and Fragility (CIBERfes), to which he belongs, together with the Research Group CTS-101. The main line of research of the Research Group has been and is the study of the mitochondria as a fundamental cellular organelle and as a therapeutic target for melatonin in various pathologies. Among them, aging, Parkinson's, sepsis, cancer and mitochondrial deficiencies have been a fundamental objective of the Group. The Research Group stands out for its high productivity and transfer to the productive sector, mainly to the pharmaceutical industry. The research has been funded by regional, national and international R&D projects, assiduously collaborating with leading international groups in their field. Several patents for new melatonin formulations have been tested in various clinical trials and transferred to the pharmaceutical industry. Another, a cream to regenerate the skin for topical application, has been transferred to Pharmamel SL, a Spin-off created by us and with international projection. Since its constitution in 1988, the CTS-101 Group has received numerous recognitions and awards for its trajectory, transfer, quality and publication citations, etc.
Research lines
- Characterization of Coenzyme Q10-deficient mouse strains. Comprehensive study of the pathophysiological consequences of deficiency in this molecule, in order to explain the heterogeneity in clinical presentations.
- Chronoinflammation and aging. Relationship between alteration of clock genes and mitochondrial dysfunction in aging. Preferential studies at the level of mitochondrial damage and prevention / recovery mechanisms of sarcopenia associated with frailty during aging
- Zebrafish as a disease model for drug screening studies to identify new drugs. Identification of neuroprotective, antioxidant, and anti-inflammatory molecules, and analysis of mitochondrial bioenergetics and phenotyping.
- Therapeutic strategies for the treatment of Coenzyme Q10 deficiency. Characterization of mouse strains deficient in Coenzyme Q
- Study of the biosynthetic pathway of Coenzyme Q10.
- Evaluation of the antioxidant and anti-inflammatory activity of melatonin and synthetic analogues. Study in experimental models (Parkinson's, sepsis and aging) and in the human clinic: studies of mitochondrial dysfunction in these models and its translation to the human clinic through clinical trials.
- Mechanisms to prevent resistance to chemo and radiotherapy. Protective role of melatonin and its endogenous metabolites in protection against damage induced by radio and chemotherapy: mainly studies at the level of mucositis, in irradiated rat models, evaluating different formulations for the topical and systemic application of melatonin and metabolites.
- Melatonin and metabolites as new pharmacological tools in cancer.
- Regulation of mitochondrial bioenergetics by melatonin. Mitochondria as a physiological and therapeutic target for melatonin. Intracellular signals in response to the action of melatonin: nuclear effects of melatonin, gene expression, mitochondrial genes and their effects on the nucleus-mitochondrial dialogue.
- Treatment of primary and secondary mitochondrial diseases. Role of mitochondria in neurodegenerative and neuromuscular diseases, cancer, diabetes, aging
Research networks
- CIBERFES Network Biomedical Research Center Fragility and Healthy Aging
Keywords
melatonin; mitochondria; aging; Parkinson; Alzheimer's; sepsis; Cancer; mucositis; innate immunity; NLRP3 inflammasome; clock genes, chronodisruption.
Pablo Ranea Robles
SERGIO LOPEZ HERRADOR
JULIA CORRAL SARASA
MARIA MARTIN ESTEBANE
CARMEN JESSICA VENEGAS MALDONADO
SERGIO ANTONIO ESQUIVEL RUIZ
LAURA JIMENEZ SANCHEZ
ELIANA BARRIOCANAL MARRIED
TOMAS BY HARO MUÑOZ
MARIA DEL LORD LOPEZ VELEZ
AGUSTIN HIDALGO GUTIERREZ
LUIS CARLOS LOPEZ GARCIA
LAURA MARTINEZ RUIZ
YOLANDA RAMIREZ CASAS
ALBA RODRIGUEZ LOPEZ
IRYNA RUSANOVA
PAULA ARANDA MARTINEZ
ELIANA BARRIOCANAL MARRIED
ELENA DIAZ MARRIED
GERMAINE ESCAMES PINK
MARISOL FERNANDEZ ORTIZ
JOSE FERNANDEZ MARTINEZ
BEATRIZ IRENE FERNANDEZ GIL
JAVIER FLORIDO RUIZ
PILAR GONZALEZ GARCIA
ANA GUERRA-LIBRAROS RITE
DARIO ACUNA CASTROVIEJO
A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in surgical patients with severe sepsis admitted to the intensive care unit
JOURNAL OF PINEAL RESEARCH, 2023;
FI: 10,3; D1
Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment
ANTIOXIDANTS, 2023;
FI: 7; Q1
The Relationship between Clock Genes, Sirtuin 1, and Mitochondrial Activity in Head and Neck Squamous Cell Cancer: Effects of Melatonin Treatment
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023;
FI: 5,6; Q1
Insights into the Role of Plasmatic and Exosomal microRNAs in Oxidative Stress-Related Metabolic Diseases
ANTIOXIDANTS, 2023;
FI: 7; Q1
Patient-derived tumor models in cancer research: Evaluation of the oncostatic effects of melatonin
BIOMEDICINE & PHARMACOTHERAPY, 2023;
FI: 7,5; Q1
Deciphering clock genes as emerging targets against aging
AGEING RESEARCH REVIEWS, 2022;
FI: 11,788; D1
Effect of 5-Azacitidine Treatment on Redox Status and Inflammatory Condition in MDS Patients
ANTIOXIDANTS, 2022;
FI: 7,675; D1
Exposure to non-persistent pesticides, BDNF, and behavioral function in adolescent males: Exploring a novel effect biomarker approach
ENVIRONMENTAL RESEARCH, 2022;
FI: 8,431; D1
Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport
JOURNAL OF PINEAL RESEARCH, 2022;
FI: 12,081; D1
Role of c-miR-21, c-miR-126, Redox Status, and Inflammatory Conditions as Potential Predictors of Vascular Damage in T2DM Patients
ANTIOXIDANTS, 2022;
FI: 7,675; D1
Animal Models of Coenzyme Q Deficiency: Mechanistic and Translational Learnings
ANTIOXIDANTS, 2021;
FI: 6,313; D1
Melatonin Targets Metabolism in Head and Neck Cancer Cells by Regulating Mitochondrial Structure and Function
ANTIOXIDANTS, 2021;
FI: 6,313; D1
Abnormalities of hydrogen sulfide and glutathione pathways in mitochondrial dysfunction
JOURNAL OF ADVANCED RESEARCH, 2021;
FI: 10,479; Q1
beta-RA Targets Mitochondrial Metabolism and Adipogenesis, Leading to Therapeutic Benefits against CoQ Deficiency and Age-Related Overweight
BIOMEDICINE, 2021;
FI: 6,081; Q1
Melatonin alleviates sepsis-induced heart injury through activating the Nrf2 pathway and inhibiting the NLRP3 inflammasome
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2021;
FI: 3; Q3
Clinical trial to test the efficacy of melatonin in COVID-19
JOURNAL OF PINEAL RESEARCH, 2020;
FI: 14,528; D1
Abnormalities of hydrogen sulfide and glutathione pathways in mitochondrial dysfunction
JOURNAL OF ADVANCED RESEARCH, 2020;
FI: 6,992; Q1
Coenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated with one carbon metabolism
HUMAN MOLECULAR GENETICS, 2020;
FI: 5,101; Q1
Coronavirus Disease 2019 (COVID-19) and Its Neuroinvasive Capacity: Is It Time for Melatonin?
Cellular and Molecular Neurobiology, 2020;
FI: 3,606; Q2
A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in patients with COVID-19 admitted to the intensive care unit (MelCOVID study): a structured summary of a study protocol
TRIALS, 2020;
FI: 1,883; Q3
Rapamycin administration is not a valid therapeutic strategy for every case of mitochondrial disease
EBIOMEDICINE, 2019;
FI: 6,68; D1
beta-RA reduces DMQ / CoQ ratio and rescues the encephalopathic phenotype in Coq9 (R239X) mice
EMBO MOLECULAR MEDICINE, 2019;
FI: 10,624; D1
Lack of NLRP3 Inflammasome Activation Reduces Age-Dependent Sarcopenia and Mitochondrial Dysfunction, Favoring the Prophylactic Effect of Melatonin
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2019;
FI: 4,711; D1
Impact of Daylight Saving Time on circadian timing system: An expert statement
EUROPEAN JOURNAL OF INTERNAL MEDICINE, 2019;
FI: 3,66; Q1
Retinoid-related orphan nuclear receptor alpha (ROR alpha) -deficient mice display morphological testicular defects
LABORATORY RESEARCH, 2019;
FI: 3,684; Q1
The Protective Effect of Melatonin Against Age-Associated, Sarcopenia-Dependent Tubular Aggregate Formation, Lactate Depletion, and Mitochondrial Changes
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2018;
FI: 4,902; D1
Combination of melatonin and rapamycin for head and neck cancer therapy: Suppression of AKT / mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation
JOURNAL OF PINEAL RESEARCH, 2018;
FI: 11,613; D1
New insights on the risk factors associated with the presence of Salmonella on pig carcasses. Lessons from small slaughterhouses
FOOD CONTROL, 2018;
FI: 3,667; D1
Sildenafil for improving outcomes in patients with corrected valvular heart disease and persistent pulmonary hypertension: a multicenter, double-blind, randomized clinical trial
EUROPEAN HEART JOURNAL, 2018;
FI: 23,425; D1
Targeting NLRP3 (Nucleotide-Binding Domain, Leucine-Rich-Containing Family, Pyrin Domain-Containing-3) Inflammasome in Cardiovascular Disorders
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2018;
FI: 6,086; D1
CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome
EMBO MOLECULAR MEDICINE, 2017;
FI: 9,249; D1
Melatonin enhances neural stem cell differentiation and engraftment by increasing mitochondrial function
JOURNAL OF PINEAL RESEARCH, 2017;
FI: 10,391; D1
Melatonin administration to wild-type mice and nontreated NLRP3 mutant mice share similar inhibition of the inflammatory response during sepsis.
JOURNAL OF PINEAL RESEARCH, 2017;
FI: 10,391; D1
Melatonin, clock genes and mitochondria in sepsis
CELLULAR AND MOLECULAR LIFE SCIENCES, 2017;
FI: 5,788; Q1
Melatonin protects rats from radiotherapy-induced small intestinal toxicity
PLOSONE, 2017;
FI: 2,806; Q1
Melatonin rescues zebrafish embryos from the parkinsonian phenotype restoring the parkin / PINK1 / DJ-1 / MUL1 network
JOURNAL OF PINEAL RESEARCH, 2016;
FI: 9,314; D1
Same molecule but different expression: aging and sepsis trigger NLRP3 inflammasome activation, a target of melatonin
JOURNAL OF PINEAL RESEARCH, 2016;
FI: 9,314; D1
Identification of morphological markers of sarcopenia at early stage of aging in skeletal muscle of mice.
EXPERIMENTAL GERONTOLOGY, 2016;
FI: 3,35; Q1
Gene Therapy Corrects Mitochondrial Dysfunction in Hematopoietic Progenitor Cells and Fibroblasts from Coq9 (R239X) Mice
PLOSONE, 2016;
FI: 3,057; Q1
Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model.
EXPERIMENTAL GERONTOLOGY, 2016;
FI: 3,35; Q1
Disruption of the NF-kappa B / NLRP3 connection by melatonin requires retinoid-related orphan receptor-alpha and blocks the septic response in mice
FASEB JOURNAL, 2015;
FI: 5,043; D1
Melatonin blunts the mitochondrial / NLRP3 connection and protects against radiation-induced oral mucositis
JOURNAL OF PINEAL RESEARCH, 2015;
FI: 9,6; D1
The clinical heterogeneity of coenzyme Q (10) deficiency results from genotypic differences in the Coq9 gene
EMBO MOLECULAR MEDICINE, 2015;
FI: 8,665; D1
Protective effects of melatonin against oxidative damage induced by Egyptian cobra (Naja haje) crude venom in rats
TROPICAL ACT, 2015;
FI: 2,27; Q1
The benefits of four weeks of melatonin treatment on circadian patterns in resistance-trained athletes
CHRONOBIOLOGY INTERNATIONAL, 2015;
FI: 3,343; Q1
Mitochondria and exo-miRNAs, therapeutic targets for the treatment of endothelial dysfunction in diabetes
Funder: UNIVERSITY OF GRANADA
File number: C-CTS-094-EGR23
Execution time: 01/01/2024 - 31/12/2026
IP: IRYNA RUSANOVA
Study of circulating microRNAs and parameters of oxidative stress and inflammation as biomarkers in basal cell carcinoma
Funder: PUBLIC FOUNDATION FOR BIOSANITARY RESEARCH OF ORIENTAL ANDALUCIA ALEJANDRO OTERO (FIBAO)
File number: INTRAIBS-2022-02
Execution time: 20/01/2023 - 30/06/2024
IP: ANA GUERRA-RITE BOOKSELLERS
Studies of cell death mechanisms and evaluation of new therapeutic targets in genetic models of Coenzyme Q deficiencies (CoQDeath)
Funder: UNIVERSITY OF GRANADA
File number: C-CTS-042-UGR23
Execution time: 01/01/2024 - 31/12/2025
IP: ELENA DIAZ MARRIED
Evaluation of exosomal microRNAs as markers and mediators of Melatonin/CoQ10/Ibedenone therapy for Endothelial Dysfunction in Type 2 Diabetes Mellitus (MT-EXO-DIABET).
Funder: UNIVERSITY OF GRANADA
File number: PP2023.PP.62
Execution time: 01/01/2024 - 31/12/2024
IP: IRYNA RUSANOVA
Deciphering the mechanisms of action of hydroxybenzoic acid derivatives in mitochondria: implications for the treatment of rare and common diseases
Funder: COUNCIL OF ECONOMIC TRANSFORMATION, INDUSTRY, KNOWLEDGE AND UNIVERSITIES
File number: PY20_00134
Execution time: 04/10/2021 - 30/06/2023
PI: LUIS CARLOS LOPEZ GARCIA
Evaluation of pharmacological treatments with high translational potential in new models of mitochondrial diseases (MitoFarma)
Funder: COUNCIL OF HEALTH AND FAMILIES
File number: PEER-0083-2020
Execution time: 28/10/2021 - 27/10/2023
PI: LUIS CARLOS LOPEZ GARCIA
Preclinical study of different melatonin formulations to prevent drug resistance associated with overexpression of ATP-dependent flow pumps.
Funder: STATE RESEARCH AGENCY
File number: PID2020-115112RB-I00
Execution time: 01/09/2021 - 31/08/2024
PI: GERMAINE ESCAMES ROSA
Gene therapy strategies for mitochondrial encephalopathies
Funder: UNIVERSITY OF GRANADA
File number: B-CTS-82-UGR20
Execution time: 01/07/2021 - 30/06/2023
PI: LUIS CARLOS LOPEZ GARCIA
New therapeutic strategy to avoid resistance to chemo and / or radiotherapy associated with mitochondrial function: Evaluation of different melatonin formulations
Funder: COUNCIL OF ECONOMIC TRANSFORMATION, INDUSTRY, KNOWLEDGE AND UNIVERSITIES
File number: P18-RT-3222
Execution time: 01/01/2020 - 31/12/2022
PI: GERMAINE ESCAMES ROSA
Analysis of the connection between clock genes, melatonin and mitochondria in the parkinson's model in zebrafish.
Funder: COUNCIL OF ECONOMIC TRANSFORMATION, INDUSTRY, KNOWLEDGE AND UNIVERSITIES
File number: P18-RT-698
Execution time: 01/01/2020 - 31/12/2022
PI: DARIO ACUÑA CASTROVIEJO
CB16 / 10/00238 CIBER DARÍO ACUÑA CASTROVIEJO
Funder: CARLOS III HEALTH INSTITUTE - FEDER
File number: CB16 / 10/00238
Execution time: 01/01/2017 - 31/12/2018
PI: DARIO ACUÑA CASTROVIEJO
The connection between clock genes, melatonin and mitochondria in sarcopenia.
Funder: CARLOS III HEALTH INSTITUTE - FEDER
File number: PI19 / 01372
Execution time: 01/01/2020 - 31/12/2022
PI: DARIO ACUÑA CASTROVIEJO
Treatment of deficiencies in Coenzyme Q: therapeutic potential of biosynthetic precursors and importance of endocrine interactions
Funder: MINISTRY OF SCIENCE, INNOVATION AND UNIVERSITIES
File number: RTI2018-093503-B-I00
Execution time: 01/01/2019 - 31/12/2022
PI: LUIS CARLOS LOPEZ GARCIA
MDA USA - New therapeutic molecules for the treatment of mitochondrial diseases
Funder: MUSCULAR DYSTROPHY ASSOCIATION - USA
File number: MDA602322
Execution time: 01/02/2019 - 31/01/2022
PI: LUIS CARLOS LOPEZ GARCIA
Phase II, single-center, double-blind, randomized, placebo-controlled clinical trial to explore the efficacy and safety of IV melatonin in patients with Covid-19 admitted to the ICU (melcovid study).
Financer: PhRMAMEL SL
Type of test: COMMERCIAL CLINICAL TRIAL
Execution time: 15/08/2020 - 06/02/2021
PI: DARIO ACUÑA CASTROVIEJO