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Thanks to the Foundation's support, Alejo Efeyan will head up the NUTRITHELIUM project, looking to find the origin of pathologies associated with obesity and how to combat them
With close to 1 million euros in funding, NUTRITHELIUM will focus on studying the endothelium, “the first organ in the body that becomes altered in the presence of obesity”
CNIO researchers Óscar Llorca, Paco Real, and Jon Zugazagoitia will participate in projects led by CIMA, CRG, and the Institute of Molecular Medicine (Portugal), respectively, to advance treatment for some of the most common tumours
In total, the Foundation has selected 30 new cutting-edge biomedical research projects in Spain and Portugal as part of the 2021 CaixaResearch call for Health Research
Alejo Efeyan, a researcher at the Spanish National Cancer Research Centre (CNIO) will head up the ambitious NUTRITHELIUM project, thanks to the funding from “la Caixa” Foundation, as part of the 2021 CaixaResearch call for Health Research. This project aims to find the origins of pathologies associated with obesity. The research, which is receiving close to 1 million euros in funding, will focus on the endothelium, “the first organ in the body that becomes altered in the presence of obesity”, to combat this disease that, alongside overweight, represents one of the biggest public health problems in the world.
As part of the same funding programme, researchers Oscar Llorca, head of the Macromolecular Complexes in DNA Damage Response Group, Paco Real, head of the Epithelial Carcinogenesis Group, and Jon Zugazagoitia from the H12O-CNIO Lung Cancer Clinical Research Unit led by Luis Paz-Ares, will receive funding to advance treatment for some of the most common tumours. These projects will be led by Maite Huarte from the Centre for Applied Medical Research (CIMA), University of Navarra, Juan Valcárcel, from the Centre for Genomic Regulation (CRG) in Barcelona, and João Barata, from the Institute of Molecular Medicine in Portugal.
The CaixaResearch call for Health Research aims to identify and promote the most promising initiatives, which offer the greatest scientific excellence and potential value and social impact, in both basic and clinical research, translational research, and innovation. A team of more than 540 international experts remotely evaluated the 644 proposals submitted this year, selecting the top 30.
Dialogue between cells is key to preventing obesity and associated diseases
Obesity and overweight have reached epidemic proportions and represent one of the biggest public health problems not only in developed countries but also in those with lower incomes. According to the World Health Organization, since 1975 obesity has almost tripled worldwide, and has increased almost five times in children and adolescents. Obesity is closely linked with a range of diseases such as diabetes, cardiovascular disease, musculoskeletal disorders, and even some cancers such as endometrial, breast, prostate, and colon, among others, and is estimated to cause 2.8 million deaths a year worldwide.
The team led by Alejo Efeyan, head of CNIO’s Metabolism and Cell Signalling Group, will study how to tackle this epidemic over the next three years. To do this, it will focus on the endothelium, “the first organ in the body that becomes altered in the presence of obesity,” explains Efeyan. Endothelium cells line the inside of blood vessels and supply oxygen and nutrients to the rest of the body’s cells. The research will be carried out alongside Mariona Graupera from the Institut Josep Carreras in Barcelona and Josep Vidal from IDIBAPS in Barcelona.
When a tissue does not get enough nutrients it activates angiogenesis, which entails the formation of new blood vessels. “Interestingly, in obese individuals, adipose tissue growth is not accompanied by an increase in vascularisation, which causes fat cells to be poorly irrigated.” As a result, this fatty tissue acts pathologically and triggers some of the problems associated with obesity.
Angiogenesis is caused by a complex dialogue between the endothelium and the cells of the tissue in which it is found, about which very little is known. “The endothelium has a unique sensitivity to nutrients and is the only tissue that needs to grow precisely when it has no nutrients to do so, and the signals it receives tell it not to,” Efeyan says. “If we force the endothelium to grow, the metabolism of fat tissue improves,” he adds.
The project will examine how endothelial cells detect and respond to nutrients, and how they communicate with the adipose tissue around them in a healthy organism and when there is obesity. “Our main objective is to restore a healthy dialogue between cells and thus correct obesity and associated diseases, such as diabetes,” he concludes.
New therapies to stop some of the most common tumours in Spain and around the world
CNIO researcher Óscar Llorca, head of the Macromolecular Complexes in DNA Damage Response Group, will study the development of new therapies against colon cancer in a project led by Maite Huarte from CIMA, University of Navarra, working alongside Fernando Moreno from the CNB-CSIC.
Recently, long non-coding RNAs (lncRNAs), molecules that regulate gene expression, have been found to contribute to the ability of cancer cells to divide, including colon cancer. The project will investigate how lncRNAs influence the development of colon cancer, which will help identify new therapeutic strategies against this type of tumour.
Llorca, an expert in high-resolution cryo-microscopy technology -a technique that has advanced dramatically and now enables molecules to be viewed in atomic detail – will study the structure of these unique RNAs. This knowledge will be essential for the development of new effective therapies against this disease.
Paco Real and Juan Valcárcel, from the CRG, who will be leading the project, will study a new tumour suppressor gene (RBM10) on which they have been working together for several years and will look for new targets to slow the progression of bladder and pancreatic cancer.
The RBM10 gene regulates development-related processes. In recent years, it has also been reported that RBM10 is mutated in 10% of lung cancer cases, 5-8% of bladder cancer cases, and in 5% of pancreatic cancer cases, among others. Together, they add up to one and a half million new cases diagnosed every year around the world.
Blocking RBM10 reduces lung cancer in animal mouse models, making it a possible target for the treatment of this disease. The project is now investigating the consequences of inactivating RBM10 in normal tissues and bladder and pancreas tumours, with the aim of identifying new therapeutic targets and slowing their progression.
Researcher Jon Zugazagoitia, from the H12O-CNIO Lung Cancer Clinical Research Unit, headed up by Luis Paz-Ares, will participate in a project led by João Barata, from the Institute of Molecular Medicine (Portugal), looking to develop new drugs for immunotherapy in lung cancer. Luis Álvarez-Vallina, from the Hospital Universitario 12 de Octubre in Madrid, will also participate in the project.
Lung cancer has the highest mortality rate of any tumour type. Immunotherapy drugs that block the PD-1 protein have revolutionised the survival rates of these patients in recent years by strengthening the immune response against cancer cells. However, many patients progress over time and develop metastases, highlighting the need for new therapeutic approaches.
The project will focus on exploring the role of the IL-7R protein in the development and therapeutic resistance of lung cancer. This protein, key to the immune response, can be used by tumour cells to promote tumour progression and resistance to blocking the PD-1 axis. Researchers will develop new strategies to block this protein and reverse resistance to immunotherapy, with the ultimate goal of developing new and better treatment strategies for patients with lung cancer who do not gain significant benefits from PD-1 axis inhibitors.