Home > Molecular Oncology and Nutritional Genomics of Cancer Group. OMYGEN

Molecular Oncology and Nutritional Genomics of Cancer Group. OMYGEN

 

PI: Ana Ramírez de Molina

Email:ana.ramirez@imdea.org Phone: +34 91 727 81 00

Address: Crta. de Canto Blanco nº 8. 28049 Madrid (España)

 

The scientific work of the group is currently focused on two research topics:

1.- Lipid metabolism alterations in cancer: identification of new biomarkers and therapeutic targets in diet-related tumors.

In this subject, the work of our group mainly focuses on the analysis of lipid metabolism alterations in cancer. Most specifically, we aim at studying the special energetic and structural requirements of tumor cells as well as identifying novel biomarkers of progression and response to therapy which may also represent new therapeutic targets.

To this end, in close collaboration with the divisions of Medical Oncology of several hospitals, we analyze clinical samples from cancer patients using state-of-the-art genomic approaches. Gene expression analysis, identification of gene variants and epigenetic regulation by microRNAs of lipid metabolism pathways are determined and associated with the clinical outcome of the disease. Furthermore, functional studies both in cells and in animal models to investigate the role of identified genes and microRNAs are performed. We are especially interested in identifying metabolic profiles associated to the disease progression and analyzing their role from in-vitro cell systems to cancer patients. These analyses are mainly focused on the identification of metabolic pathways that may constitute novel targets for the development of future cancer therapies, as well as the genetic basis of the relationship between obesity and associated metabolic disorders and cancer.

2.- Study of the activity and mechanism of action of bioactive compounds as potential effective supplements in preventing and/or treating cancer.

We evaluate the activity and molecular mechanism of action of bioactive compounds that may have a therapeutic use in cancer, either alone or in combination with existing chemotherapy. The aim is to establish the scientific basis for the development of nutritional supplements that may exert a beneficial effect on the disease.

In close collaboration with Universidad Autónoma de Madrid, specifically with researches from the group of Bioactive Food Ingredients of the Institute of Food Science Research, we design and characterize different formulations of bioactive compounds, and combine genomics and functional studies in order to determine the effect and target populations for personalized therapeutic use of the mentioned formulations.

Recently, we have evaluated the effect on gastrointestinal tumor progression of a supercritical extract of rosemary (which has been shown to be safe for human use by EFSA). Such extract inhibits proliferation, induces cell death, and potentiates the effect of chemotherapy, both in sensitive and resistant colon tumor cell lines. Furthermore, we have identified key players of its underlying molecular mechanism as well as the characteristics of potential patients more likely to benefit most from a nutritional supplement based on this extract.

Team

Publications (last 4 years)

2016

de la Iglesia R, Loria-Kohen V, Zulet MA, Martinez JA, Reglero G, Ramirez de Molina A. Dietary Strategies Implicated in the Prevention and Treatment of Metabolic Syndrome. Int J Mol Sci. 2016 Nov 10;17(11). pii: E1877. Review. PMID: 27834920.
 
Mendiola M, Martínez-Marin V, Herranz J, Heredia V, Yébenes L, Zamora P, Castelo B, Pinto Á, Miguel M, Díaz E, Gámez A, Fresno JÁ, Ramírez de Molina A, Hardisson D, Espinosa E, Redondo A. Predictive value of angiogenesis-related gene profiling in patients with HER2-negative metastatic breast cancer treated with bevacizumab and weekly paclitaxel. Oncotarget. 2016 Apr 26;7(17):24217-27. doi: 10.18632/oncotarget.8128. PMID: 26992213.
 
Loria-Kohen V, Espinosa-Salinas I, Marcos-Pasero H, Lourenço-Nogueira T, Herranz J, Molina S, Reglero G, Ramirez de Molina A. Polymorphism in the CLOCK gene may influence the effect of fat intake reduction on weight loss. Nutrition. 2016 Apr;32(4):453-60. doi: 10.1016/j.nut.2015.10.013. PMID: 26690565.
 
Gómez de Cedrón M, Ramírez de Molina A. Microtargeting cancer metabolism: opening new therapeutic windows based on lipid metabolism. J Lipid Res. 2016 Feb;57(2):193-206. doi: 10.1194/jlr.R061812. Review. PMID: 26630911.
 

2015

Sánchez-Martínez R, Gómez de Cedrón M, Vargas T, Molina S, García B, Herranz J, Álvarez-Fernández M, Moreno-Rubio J, Reglero G, Pérez-Moreno M, Feliu J, Malumbres M, Ramírez de Molina A. A link between lipid metabolism and epithelial-mesenchymal transition provides a target for combined drug therapy in colon cancer. Oncotarget, 2015 Nov 17;6(36):38719-36. doi: 10.18632/oncotarget.5340
 
González-Vallinas M, Reglero G and Ramírez de Molina A. Rosemary (Rosmarinus officinalis L.) extract as a potential complementary agent in anticancer therapy. In press. Nutrition and Cancer, 2015. (DOI:10.1080/01635581.2015.1082110)
 
Ramirez De Molina A, Vargas T, Molina S, Sanchez J, Martinez-Romero J, Gonzalez-Vallinas M, Martín-Hernández R, Sanchez-Martinez R, Gomez de Cedron M, Davalos A, Calani L, Del Rio D, Gonzalez-Sarrias A, Espin JC, Tomas-Barberan FA, Reglero G. The ellagic acid derivative 4,4'-Di-O-methylellagic acid as a promising molecule in colorectal cancer therapy.J Pharmacol Exp Ther. 2015 Mar 10. pii: jpet.114.221796. [Epub ahead of print]. PMID: 25758919
 
Vargas T, Moreno-Rubio J, Herranz J, Cejas P, Molina S, González-Vallinas M, Mendiola M, Burgos E, Aguayo C, Custodio AB, Machado I, Ramos D, Gironella M, Espinosa-Salinas I, Ramos R, Martín-Hernández R, Risueño A, De Las Rivas J, Reglero G, Yaya R, Fernández-Martos C, Aparicio J, Maurel J, Feliu J, Ramírez de Molina A. ColoLipidGene: signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients. Oncotarget, 2015 Feb 6. [Epub ahead of print] No abstract available. PMID: 25749516
 
González-Vallinas M, Vargas T, Moreno-Rubio J, Molina S, Herranz J, Cejas P, Burgos E, Aguayo C, Custodio A, Reglero G, Feliu J, Ramírez de Molina A. Clinical relevance of the differential expression of the glycosyltransferase gene GCNT3 in colon cancer. Eur J Cancer. 2015 Jan;51(1):1-8. doi: 10.1016/j.ejca.2014.10.021. Epub 2014 Nov 11. PMID: 25466507
 

2014

González-Vallinas M, Molina S, Vicente G, Sánchez-Martínez R, Vargas T, García-Risco MR, Fornari T, Reglero G, Ramírez de Molina A. Modulation of estrogen and epidermal growth factor receptors by rosemary extract in breast cancer cells. Electrophoresis. 2014Epub  Feb 25. Volumen: 35   Número: 11   Número especial: SI   Páginas: 1719-1727 
 
González-Vallinas M, Molina S, Vicente G, Zarza V, Martín-Hernández R, García-Risco MR, Fornari T, Reglero G, Ramírez de Molina A. Expression of MicroRNA-15b and the Glycosyltransferase GCNT3 Correlates with Antitumor Efficacy of Rosemary Diterpenes in Colon and Pancreatic Cancer. PLoS One. 2014 Jun 03; 9(6)
 
Vargas T, Moreno-Rubio J, Herranz J, Cejas P, Molina S, González-Vallinas M, Ramos R, Burgos E, Aguayo C, Custodio AB, Reglero G, Feliu J, Ramírez de Molina A. Genes associated with metabolic syndrome predict disease-free survival in stage II colorectal cancer patients. A novel link between metabolic dysregulation and colorectal cancer. Mol Oncol. 2014 Jun 10. pii: S1574-7891(14)00122-7. doi: 10.1016/j.molonc.2014.05.015. (Artículo destacado en la portada)
 
González-Vallinas M, Vargas T, Moreno-Rubio J, Molina S, Herranz J, Cejas P, Burgos E, Aguayo C, Custodio A, Reglero G, Feliu J, Ramírez de Molina A. Clinical relevance of the differential expression of the glycosyltransferase gene GCNT3 in colon cancer. Eur J Cancer. 2014 Nov 11. pii: S0959-8049(14)01057-0. doi: 10.1016/j.ejca.2014.10.021. [Epub ahead of print]
 
Loria-Kohen V, Espinosa-Salinas I, Ramirez de Molina A, Casas-Agustench P, Herranz J, Molina S, Fonoll J, Olivares M, Lara-Villoslada F, Reglero G, Ordovas JM. A genetic variant of PPARA modulates cardiovascular risk biomarkers after milk consumption. Nutrition. 2014 Oct;30(10):1144-50. doi: 10.1016/j.nut.2014.02.012. Epub 2014 Mar 12. PubMed PMID: 24976416.
 
Loria-Kohen V., Lourenço-Nogueira T., Espinosa-Salinas I., Marín F. R., Soler-Rivas C., Ramirez de Molina A.. Nutritional and Functional Properties of Edible Mushrooms: A Food with Promising Health Claims. Journal of Pharmacy and Nutrition Sciences, Vol 4, No 3 (2014). DOI: http://dx.doi.org/10.6000/1927-5951.2014.04.03.4
 
2013
 
González‐Vallinas, M., González‐Castejón, M., Rodríguez‐Casado, A. & Ramírez de Molina, A. Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising perspectives.
Nutr Rev. 2013 Sep;71(9):585-99.
 
S. Molina, M.I. Moran-Valero, D. Martin, T. Vargas, CF Torres, A Ramirez de Molina  and G Reglero. Antiproliferative effect of alkylglycerols as vehicles of butyric acid on colon cancer cells.
Chemistry and Physics of Lipids. 2013  Aug 21;175-176C:50-56.
 
De la Cueva A, Ramírez de Molina A, Alvarez-Ayerza N, Ramos MA, Cebrián A, Del Pulgar TG, Lacal JC. Combined 5-FU and ChoKα Inhibitors as a New Alternative Therapy of Colorectal Cancer: Evidence in Human Tumor-Derived Cell Lines and Mouse Xenografts.
PLoS One. 2013 Jun 10;8(6):e64961.
 
González-Vallinas M, Molina S, Vicente G, de la Cueva A, Vargas T, Santoyo S, García-Risco M, Fornari T, Reglero G,  Ramírez de Molina A. Antitumor effect of 5-fluorouracil is enhanced by rosemary extract in both drug sensitive and resistant colon cancer cells.
Pharmacological Research, 2013, 1;72C:61-68.
 
Vicente G,  Molina S, González-Vallinas M, García-Risco MR, Fornari T, Reglero G, Ramírez de Molina A. Supercritical rosemary extracts, their antioxidant activity and effect on hepatic tumor progression.
The Journal of Supercritical fluids, 2013, 79: 101–108.
 
2012
 
Daimiel L, Vargas T, Ramírez de Molina A. Nutritional Genomics: characterization of the effect of bioactive molecules in lipid metabolism applied to food science.
Electrophoresis. 2012; 33(15):2266-89
 
Ramírez de Molina A. Choline Kinase.
Encyclopedia of cancer, 2012 (http://www.springerreference.com/docs/html/chapterdbid/306844.html)
 
Ramírez de Molina A, de la Cueva A, Machado-Pinilla R, Rodriguez-Fanjul V, Del Pulgar TG, Cebrian A, Perona R, Lacal JC. Acid Ceramidase as a Chemotherapeutic Target to Overcome Resistance to the Antitumoral Effect of Choline Kinase α Inhibition.
Curr Cancer Drug Targets. 2012;12(6):617-24.

Patents

P201131733/ PCT/ES2012/070750: Composiciones de extracto de romero para el tratamiento del cáncer. Organismo: IMDEA Alimentación y UAM. Inventores: Ana Ramírez de Molina, Susana Molina, Margarita González-Vallinas, Tiziana Fornari, Mónica Rodríguez García-Risco, Guillermo Reglero.

P201231918. Métodos y Kits para el pronóstico del cáncer colorectal. Organismo: IMDEA Alimentación, Hospital La Paz. Inventores. Ana Ramírez de Molina, Teodoro Vargas, Susana Molina, Margarita González-Vallinas, Guillermo Reglero, Paloma Cejas, Juan Moreno Rubio, Jaime Feliu