José Manuel Rodrigo Muñoz
Julio Rodríguez Villanueva Award for Best Doctoral Thesis
November 21, 2022
"The collaborative and integrative work of basic and clinical researchers is the main engine of progress in biomedicine."
Dr. José Manuel Rodrigo Muñoz is a CIBER postdoctoral researcher working in the immunoallergy research laboratory at the Instituto de Investigación Sanitaria de la Fundación Jimenez Diaz (IIS-FJD). He holds a degree in Health Biology from the University of Alcalá de Henares and a Master's in Immunology Research.
Dr. Rodrigo Muñoz defended his doctoral thesis at the Complutense University of Madrid in May 2021, under the supervision of Dr. Victoria del Pozo. During his doctoral research, he was awarded a scholarship from the Conchita Rábago Foundation of the IIS-FJD and received a PFIS fellowship from the Carlos III Health Institute. The results of his research have been presented at national and European conferences and published in first-quartile journals in the fields of allergy and clinical immunology. He has also contributed to laboratory teaching for allergy residents at the Fundación Jiménez Díaz University Hospital, as well as other national hospitals.
Project Summary and Clinical Practice Relevance
Doctoral Thesis: MicroRNAs in Asthma: Biomarkers of Asthma Disease, Severity Phenotypes, and Potential Therapeutic Tools
Asthma is a chronic respiratory disease characterized by cough, wheezing, and shortness of breath caused by the exacerbation of the physiological inflammatory response, which involves, among many other molecules, microRNAs (miRNAs). These non-coding RNA molecules are part of the epigenetic regulation of gene expression as they can bind to complementary messenger RNA, inhibiting translation. This involves the regulation of cellular functions and the immune response in asthma. Moreover, miRNAs are associated with pathological states and are highly resistant to degradation, characteristics that make them excellent biomarkers.
The aim of this thesis was to study the expression of a miRNA profile in serum samples from individuals with asthma, to determine its potential use as a biomarker and to investigate the individual function of miRNAs in the pathophysiology of asthma.
MiRNA expression was studied in the serum of healthy individuals, asthmatics, individuals with chronic obstructive pulmonary disease (COPD), and those with asthma-COPD overlap syndrome (ACO), using statistical and bioinformatic models. Additionally, by using miRNA mimics and inhibitors, the function of miRNAs in airway remodeling in asthma was assessed. The differential expression of a miRNA profile was identified in the serum of asthmatic subjects compared to healthy individuals, COPD patients, and those with ACO, which could differentiate and classify asthmatic patients according to disease severity in a bioinformatic model. Among the miRNAs with the highest diagnostic capability for asthma, miR-185-5p stands out due to its serum values. This miRNA, in addition to being a good asthma biomarker, can regulate the secretion of periostin by bronchial epithelial and muscle cells, and modulates the contractile capacity of bronchial muscle cells through the regulation of their target proteins with contractile functions: RhoA and CDC42. miR-185-5p is likely part of a negative feedback loop involved in controlling airway remodeling, and its expression is insufficient in asthma.
Therefore, the studies conducted within the scope of this thesis highlight the existence of a serum miRNA profile in asthma patients that could be used as a biomarker for asthma severity phenotype, as well as for diagnosis compared to healthy individuals and other pulmonary diseases such as COPD or asthma-COPD overlap. Future research on the detection of these serum miRNA profiles using validation teams and various detection techniques could lead to the eventual clinical application of these miRNAs in asthma diagnosis.
Furthermore, as Dr. José Manuel Rodrigo Muñoz indicates, "there is a certain therapeutic potential of microRNAs in asthma pathology due to the results obtained regarding the function of miR-185-5p, which is capable of regulating both the contraction of lung muscle cells and the synthesis of periostin, a pro-inflammatory molecule involved in epithelial remodeling. However, further translation to in vivo models, such as mouse models, as well as more clinical tools, molecular adaptations, and human clinical trials, are required for microRNAs to be viable for asthma therapy."
Dr. José Manuel Rodrigo Muñoz is a CIBER postdoctoral researcher working in the immunoallergy research laboratory at the Instituto de Investigación Sanitaria de la Fundación Jimenez Diaz (IIS-FJD). He holds a degree in Health Biology from the University of Alcalá de Henares and a Master's in Immunology Research.
Dr. Rodrigo Muñoz defended his doctoral thesis at the Complutense University of Madrid in May 2021, under the supervision of Dr. Victoria del Pozo. During his doctoral research, he was awarded a scholarship from the Conchita Rábago Foundation of the IIS-FJD and received a PFIS fellowship from the Carlos III Health Institute. The results of his research have been presented at national and European conferences and published in first-quartile journals in the fields of allergy and clinical immunology. He has also contributed to laboratory teaching for allergy residents at the Fundación Jiménez Díaz University Hospital, as well as other national hospitals.