Jose Luis Cabrera Alarcón, PhD

During four years as a postdoctoral researcher in the GENOXPHOS group, we have analyzed the landscape of variability for the oxphos system in human populations and in mouse samples. In addition, we have explored the existence of restraining mechanisms of this variability, at the transcriptional level. We are currently studying the possible effect on the fitness of the OxPhos system of point mutations or combinations of variants in its components.

Jose Luis Cabrera Alarcón, PhD Image


Carolina García-Poyatos, PhD

Carolina García-Poyatos, PhDIn my second year as a postdoctoral researcher in the GENOXPHOS lab, I am working in the role of alternative isoforms of complex IV, specifically the Cox7a family. The alternative Cox7a subunits contribute to complex IV with a distinct supramolecular organization, appearing in monomeric, dimer, multimer and super-assembled with other complexes forming the Q-respirasome and the N-respirasome (Cogliati and Calvo, et al. Nature 2016). Using zebrafish and mouse models, we have observed that the supramolecular structures of complex IV have different metabolic and physiological functions, ranging from metabolic maturation necessary for correct tissue physiology, to plasticity and adaptation to different metabolic requirements.Carolina García-Poyatos, PhD


Pablo Hernansanz Agustín, PhD

Pablo Hernansanz Agustín, PhDMy research is focused on the role of Na+ in the regulation the oxidative phosphorylation (OXPHOS) system related to bioenergetics, the formation of supercomplexes, ubiquinone and pool behaviour, electron flux and the production of reactive oxygen species (ROS). We recently published that Na+ can act as a second messenger by regulating the inner mitochondrial membrane (IMM) fluidity, lowering the electron transfer from complex II to complex III, but not inside supercomplexes, and increasing the production of ROS by complex III. This mechanism controls acute hypoxic adaptations such as hypoxic pulmonary vasoconstriction. Now I am further exploring the role of Na+ regulating the OXPHOS in terms of bioenergetics, with particular interest in the onset and/or development of a variety physiological and pathophysiological scenarios.

Pablo Hernansanz Agustín, PhD image


Marta Pérez-Hernández Durán, PhD

Marta Pérez-Hernández Durán

After defending my PhD at the University Complutense of Madrid (Spain) and my first postdoctoral fellowship at New York University (U.S.) studying various cardiomyopathies, I joined the GENOXPHOS group to study the role of the tyrosine kinase Fgr in the heart.

Previous studies in our laboratory have shown that Fgr, upon stress, phosphorylates complex II of the electron transport chain. This leads to a change in the metabolism of the cell, which ultimately leads to inflammation.

My project studies the possible cardioprotective effect of inhibiting Fgr to reduce cardiac inflammation. Our results could then serve as a foundation to explore treatment of other cardiac conditions in which an inflammatory component plays an important role such as myocardial infarction, atherosclerosis or arrhythmogenic right ventricular cardiomyopathy. In the latter, in collaboration with Prof. Delmar (New York University) we have observed that Fgr inhibition in vitro is protective.

Moreover, we are establishing new techniques to 1) study the heart ex vivo, and 2) study mitochondrial supercomplexes using super resolution microscopy.

 


Marta Pérez-Hernández Durán 1

 

 

María Concepción Jiménez Gómez, PhD

María Concepción Jiménez Gómez, PhDAfter finishind my PhD in Molecular Biology at the UAM, I did a postdoctoral period of seven years in the research team of a biotech company. After this period, I joined the GENOXPHOS group. I first started with project management.

María Concepción Jiménez Gómez, PhD, figure 1

With the pass of time and the development of the projects I started to explore and develop the translational potential of the group's basic research discoveries as well as the translation and patentability potential of group techniques and knowledge developed within the group to make them available to industry partners. GENOXPHOS is currently developing projects with leaders in the pharmaceutical industry, including Astrazeneca and Minovia Therapeutics. Also, I supervise students, in fact this year one of them has defended his thesis, under my co-direction.
María Concepción Jiménez Gómez, PhD, figure 2



Andréa Curtabbi, MD

Andréa Curtabbi, MDI joined GENOXPHOS lab after obtaining my MD degree from the University of Turin. My research is focused in understanding how dysfunction in oxidative phosphorylation affects human health. By using mouse models of Leigh syndrome, a heritable mitochondrial disorder, I am investigating how genetic defects respiratory complexes lead to neuromuscular pathologies. In collaboration with the proteomic unit at CNIC, I am looking for candidate genes that are important for respiratory complex I stability and activity that may have a role in human disease. I am also studying the role of ATP synthase oligomerization in mitochondrial cristae ultrastructure and tissue homeostasis.

Andréa Curtabbi, MD image


Yolanda Martí Mateos

Yolanda Martí MateosAfter five years at GENOXPHOS laboratory working on OMA1-targeted therapies in preclinical models I defended my PhD thesis in Molecular Biosciences, becoming a postdoctoral researcher. Currently, I am investigating the application of diverse heart failure models and the long-term consequences of OMA1 ablation in vivo, aiming to assess its viability as a therapeutic target.

OMA1 is a mitochondrial protease that participates in various processes: the regulation of mitochondrial structure, the activation of the integrated stress response and, eventually, the cell’s entry to apoptosis. In 2018, our group demonstrated that the absence of this protein in three models of heart failure preventively results in cardioprotection. Therefore, our current efforts are focused in proving the therapeutic potential of this target and exploring the possible adverse effects that the absence of this protein might have, due to the marked translational nature of this project.

Yolanda Martí Mateos image


Raquel Justo Méndez

I am performing my PhD on the variability of mitochondrial DNA (mtDNA) and its effect in the OXPHOS system behavior and mitochondrial ROS (mtROS) generation. Recent results of GENOXPHOS group demonstrate that different combinations of nuclear DNA and mitochondrial DNA promote differences in mitochondrial electron‐transport‐chain and thus, in oxidative phosphorylation performance. My research is focused on how the mitochondrial genetics and different mitochondrial metabolic signatures impacts in the global process of ageing and frailty. By using a mouse model of deficient in the proofreading capacity of the mitochondria DNA polymerase we also explore how different mitochondrial function affect the aging process.

Raquel Justo Méndez image


Carmen Morales Vidal

Carmen Morales VidalAfter graduating in Biochemistry and Biomedical Sciences at the University of Valencia in 2020, I joined the Genoxphos group as a master's student and, finally, as a predoctoral researcher. My thesis project focuses on two mitochondrial supercomplexes other than respirasomes, I+IV and I+III2, whose function is not yet resolved. Regarding I+IV, we are carrying out proteomic analyses in order to analyze the composition of subunits, and we have also established collaborations to try to solve structurally this supercomplex. Regarding I+III2, my work aims to study the importance of the association between CI and CIII, in addition to shedding light on the controversial existence of separate pools of ubiquinone: one general, available for free complexes and other enzymes, and another confined within supercomplexes and used preferentially by their constituents. Therefore, I am currently generating cell lines where the interaction between CI and CIII is interrupted, in order to deepen the reason behind the associations between respiratory complexes.

Carmen Morales Vidal

Xiaotong Hong

Xiaotong Hong

Xiaotong Hong is a PhD student from Pompeu Fabra University (UPF), co-directed by Dr. Pura Muñoz-Cánoves. In her PhD project, she aims to understand the role of mitochondrial dynamics in muscle stem cell (also called satellite cells) during muscle regeneration. Mitochondrial dynamics is regulated by various dynamin-family proteins such as mitofusin 1 (MFN1), optic atrophy 1 (OPA1) and dynamin-related protein 1 (DRP1). Loss of function of these proteins can lead to disturbed mitochondrial morphology and function. By ablating these mitochondrial-shaping proteins in satellite cells and studying the muscle regeneration upon injury, we can decipher how mitochondrial dynamics in the stem cells affects the regeneration of the tissue.


Xiaotong Hong

 


Macarena de Andrés Laguillo

Macarena de Andrés LaguilloDespite being one of the cell types with the highest oxygen availability, endothelial cells have a highly anaerobic metabolism. For years the role of the electronic transport chain in blood vessel development (angiogenesis) was considered little more than anecdotal, a dogma that has begun to be questioned in recent years.

My project, under the direction of Rui Benedito and co-direction of José Antonio Enríquez, focuses on characterizing how alterations in mitochondrial metabolism and the production of reactive oxygen species (ROS) affect and modulate angiogenesis in both physiological and pathological contexts.

The cross-sectional presence of angiogenesis in various pathologies (cancer, stroke, heart attacks, malformations, etc.) makes the understanding of the processes that govern it, something highly valued and necessary in the treatment of these diseases.

This project will take advantage of the experience of both groups using advanced genetic models, such as functional mosaics, to carry out a deep and detailed characterization of the mechanisms that underlie the mitochondrial modulation of angiogenesis.

Macarena de Andrés Laguillo 1

Macarena de Andrés Laguillo 2


Esther García Domínguez

Esther García Dominguez

I graduated in Physical Activity and Sports Sciences and am doing a PhD in Exercise Physiology in the FRESHAGE group of the University of Valencia. My thesis project focuses on studying the molecular mechanisms responsible for geriatric frailty syndrome and the possible interventions that prevent, delay or reverse its appearance, as well as identify early biomarkers of frailty that allow its early detection and aid in its clinical diagnosis. Mainly, I study physical exercise programs, both in humans and in animal experimental models, and the role of glucose-6-phosphate dehydrogenase as strategies against frailty.

I joined the GENOXPHOS group as visiting scientist during my second year of doctorate to start a collaboration with the Valencia group. This allows me to study the implication of mitochondrial structural and functional changes in the appearance and progression of frailty, as well as to know if interventions for the prevention and treatment of frailty have an effect on the function and content of mitochondria.

Esther García Domínguez


Raquel Martínez de Mena, PhD

Raquel Martínez de Mena, PhD
After completing my PdD in Sciences at the Universidad Autónoma de Madrid and after performing several years of  research on brown adipose tissue and thyroid hormones at the IIB Alberto Sols in Madrid, I joined Dr José Antonio Enriquez´s group to work as a technician specialized in cell culture and biochemical and molecular biology techniques in the field of Functional Genetics of the Oxidative Phosphorylation System.


Raquel Martínez de Mena, PhD image
Modified from Sci Adv. 2020 Jul 29;6(31)


María del Mar Muñoz Hernández

I joined GENOXPHOS after finishing my training as laboratory technician. In the group I am responsible for several aspects of the research with special expertise in handling experimental animal models including husbandry breeding and genetic characterization and with special training in surgery, metabolic and behavioral analysis.

María del Mar Muñoz Hernández image


Eva Raquel Martínez

Eva Raquel Martínez

I joined GENOXPHOS after several years of work in different research laboratories. I am working as a technician with special expertise in histological analysis to visualize cellular damage in different tissues. I am trained also in molecular biology methods and in handling experimental animal models.


 

Eva Raquel Martínez image

Marina Rosa Moreno

Eva Raquel MartínezAfter graduating in biochemistry by the Universidad Autonoma de Madrid and performing my master's degree in bioinformatics by the Universidad Autonoma de Barcelona, I started my predoctoral studies in GENOXPHO's group. Mi thesis project is centered in studying the effect of the mitochondrial haplogroup variants in the structure of the electron transport chain complexes by using in silico models of these proteins.

Using computational modeling tools we are able to predict the folding of the electron transport chain proteins, which present subunits codified both in the nuclear and in the mitochondrial DNAs. Then, using these models we can predict the effect that mutations, ligand incorporation or binding of other proteins can have in the protein structure.
Mitochondrial haplogroups have been associated with various diseases, however not much is known about the differences between these genomes at molecular level. The aim of this project is to characterize the effect of these genetic variants at structural level using in silico models of the electron transport chain proteins belonging to the diferent mitochondrial haplogroups and having the same nuclear environment. Also, these mitochondrial complexes models are used to predict different structural effects of the respiratory chain.
 

Paula Fernández-Montes

Paula Fernández-Montes

After graduating in Biology at the Universidad Autónoma de Madrid, I joined GENOXPHOS group as a master´s student. Currently, I am a predoctoral researcher studying the superassembly of Complex IV. CIV (cytochrome oxidase c) is the last complex of the electron transport chain and undergoes a high level of regulation. The main objective of my project is to understand the physiological and molecular role of the different isoforms of the COX7A family (COX7A1, COX7A2 and COX7A2L or SCAF1) in the superassembly of complex IV and, therefore, in cellular metabolism. This family of proteins is interchangeable and the presence of one affects the conformation of CIV (Cogliati and Calvo, et al. Nature 2016). Using murine and cellular models, we are studying how the lack of one or two of the isoforms has an impact at the molecular level, as well as its effect on the viability of the organism.

Paula Fernández-Montes

Michaela  Veliova

Michaela Veliova

After finishing my PhD at the University of California, Los Angeles, I joined the GENOXPHOS lab in 2022 for my postdoctoral training. My research is focused on intracellular heterogeneity of mitochondria. Numerous studies have shown functionally distinct subpopulations of mitochondria withing a cell in various tissue types, however the mechanisms by which mitochondria can differentiate into subpopulations remains unknown. Therefore, my project aims to understand the regulation of differential protein expression in mitochondrial subpopulations in the brown adipose tissue and the heart.

Michaela Veliova