The laboratory of “Mitochondrial Regulation of Cell Death”, directed by Jose Carlos Fernandez-Checa, was created in 1992 upon the incorporation of Jose C. Fernandez-Checa and Carmen Garcia Ruiz from the University of Los Angeles (UCLA) and the University of Southern California (USC), where they worked for almost 10 years as Faculty, to the University of Barcelona and the Liver Unit of the Hospital Clinic i Provincial of Barcelona. The laboratory is nowadays based at the Institute of Biomedical Research of Barcelona from the Spanish Research Council (IIBB-CSIC) and at the “Instituto de Investigaciones Biomédicas Agustí Pi i Sunyer” (IDIBAPS) in Barcelona. Throughout these 30 years, many scientists have contributed with great effort and dedication to an extraordinary academic production both in magnitude and in quality.There have been many collaborators who, with their commitment and dedication, have contributed to a first-rate academic production. A large number of pre and postdoctoral students, both national and international, have been trained and the laboratory has directed 32 doctoral theses, some recognized with the Extraordinary Prize and others with International Mention. Many of them now lead their own research teams, evidencing the great educational work carried out by the group.
The work conducted in the group throughout these years has been highly effective, having contributed to the more than 70 joint publications published in high-impact journals. Our group that actively participates and attends international and national conferences to share our work and establish links with other researchers. It is a highly internationalized group, reflected by the extensive collaborations it maintains with various centers and universities throughout different countries: Prof. M Karin (University of California, San Diego, USA), Prof. Neil Kaplowitz ( University of Southern California, Los Angeles, USA), Prof. M Grompe (Oregon Stem Cell Centre, Oregon, USA), Prof. S Zalungo (Pontifical Catholic University of Chile, Chile), Prof. MA Avila (Center for Applied Medical Research University of Navarra, Spain), Prof. JM Mato (CIC bioGUNE, Derio, Spain), Prof. C Gutiérrez (Metropolitan University of Mexico), Prof. I. Bergheim (University of Vienna), Prof. M Sorice (Sapienza University of Rome, Rome, Italy), and a long etcetera.
In parallel, the group participates in various scientific outreach activities and actively contributes to society by participating in public engagement activities such as "Science Week", seminars, or master classes for high school students.
The overarching goal of the “Mitochondrial Regulation of Cell Death” laboratory is to expand the knowledge of the biological mechanisms that modulate mitochondrial function and how this modulation contributes to hepatic and neurodegenerative diseases with the aim of improving current medical practice, from diagnosis to treatment, of such disorders.
The group focuses on the study of the contribution of lipids, such as cholesterol, in regulating the function of the mitochondria. Healthy mitochondrial function is essential for cell survival. That is why the laboratory investigates how variations in mitochondrial activity contributes to the development of liver diseases, such as steatohepatitis, and its progression towards liver cancer, and neurodegenerative diseases such as Alzheimer's (AD) or Niemann Pick Type C (NPC), with the aim of identifying new therapeutic targets and design better and more specific drugs.
The laboratory uses cellular and mice models to investigate the cellular and molecular bases related to the progression of liver disease and neurodegeneration and it applies therapeutic interventions to improve the final outcome of the disorders. It is equipped with genetically modified mice that allow the study of different proteins in specific cell-types. In addition, an innovative mouse model transplanted with human liver cells has been generated in the group, which enables the realization of studies within a scenario that is more similar to that of the patient.
Using such approaches, one of the group’s most important discoveries has been how mitochondrial cholesterol influences the development of liver diseases and neuronal function. The various lines of research in the laboratory are focused on improving our understanding about the biological mechanisms controlling these conditions in different pathological situations, in order to design new drugs or to reuse existing ones for treatment.
Lines of research
Sphingolipid metabolism is important to regulate the machinery of cell death and releases the molecular culprits involved in the execution of this process in its various environments, which include apoptosis, necrosis, and necroapoptosis.
Since cholesterol is an important factor that determines the structural properties of lipid bilayers, one of our goals was to understand the mechanisms underlying intracellular cholesterol trafficking in mitochondria and its impact on liver and neurodegenerative diseases (such as Alzheimer's or Niemann Pick disease) by generating genetic models deleting the StARD1 protein, a mitochondrial cholesterol transporter protein, in specific cells.
Since the biology of mice and humans is different, we have developed a mouse model with a humanized liver, which can increase the translational importance of experimental research as it allows carrying out studies in a more similar setting to that of patients.
To determine the role of mutual regulation between sphingolipids and cholesterol in lysosomes and mitochondrial turnover in the regulation of drug-induced liver injury.
Our objective is to study the impact of mitochondrial cholesterol and glycosphingolipids on the stabilization/activation of HIF1a, its impact on the progression to alcoholic and non-alcoholic steatohepatitis (ASH/NASH) and on the progression of NASH to hepatocellular carcinoma.
Our purpose is to understand the impact of mitochondrial cholesterol on adipose tissue and muscle, and its interaction on insulin resistance and nonalcoholic steatohepatitis.
This line of research focuses on the identification of new therapeutic targets for the treatment of liver and kidney diseases by studying the cellular and molecular pathways involved in the progression of the disease, with special emphasis on the biology of proteases.
Past lab members:
Albert Morales Muñoz
Mº del Carmen Blasco
Josep María Lluïs Duquez
Roberto Alejandro Rabinovich
Luis Enrique Gómez-Quiroz
Joan Montero Boronat
Laura Llacuna Duran
Anna Fernández Fernández
Nuria Tarrats Font
Laura Martínez Gili
Elisabet Barbero Camps
Anna Baulies Domenech
Natalia Nuño Lambarri
Sandra Torres Núñez
Mª Carmen Vallejo
Estel Solsona i Vilarrasa
Prof. N Kaplowitz; University of Southern California, Los Angeles. USA
Prof. H Tsukamoto; University of Southern California, Los Angeles. USA
Prof. MA Avila; Centro de Investigación Médica Aplicada de la Universidad de Navarra, España
Prof. JM Mato; CIC bioGUNE, Derio, España
Prof. M Grompe; Oregon Stem Cell Centre, Oregon. USA
Prof. R Bataller; Pittsburg Liver Research Centre
Dr. J Caballeria; Hospital Clinic, Barcelona, España
Prof. M Sorice; Sapienza University of Rome, Roma, Italia
Prof. S Zalungo; Pontifical Catholic University of Chile, Chile
Prof. C Gutierrez; Universidad Metropolitana de México
Prof. I. Bergheim; University of Vienna
The research of the group is funded through competitive public and private calls hold by entities like: