Since I obtained my degree in Biochemistry (2001) at
the University of Barcelona (UB), I have actively pursued a career in
glycobiology, especially on the analysis of glycoproteins involved in human
diseases. In 2002 I was granted with a predoctoral scholarship from the IMIM
(Hospital del Mar Research Institute) to fund a PhD in Biomedicine. In 2008, I
finished my doctoral thesis entitled "Structural analysis of
erythropoietin glycans" at the Pompeu Fabra University of Barcelona.
Once completed my PhD, I had a two-year post-doctoral
fellowship in the PRBB of Barcelona. There, I developed my research into
glycoprotein analyses, consolidating my experience in the analytical techniques
(electrophoretic, chromatographic and mass spectrometry) commonly used in glycoproteomic
studies.
In 2011, I moved to the University of Girona (UdG) to
join the group led by Dr. R. Peracaula and since then, I have been
participating in the group's projects involved in glycosylation and cancer
biomarkers discovery (prostate and pancreatic cancer). This has allowed me to
expand my training and consolidate my knowledge in the field of glycobiology
and in the molecular basis of cancer.
During my pre and post-doctoral studies, I stayed at
two of the international glycobiology research centers of excellence, such as
the Bijvoet Center for Biomolecular Research. Department of Bio-Organic
Chemistry of Utrecht in The Netherlands, led by Dr. H. Kamerling (2005) and the
National Institute for Research and Training in Bioprocessing (NIBRT), Dublin,
Ireland, led by Dr. P. Rudd and Dr. R. Saldova (2012). In addition, within the
framework of technology transfer, I did a short-stay at the pharmaceutical
company Roche Diagnostics in Penzberg, Germany (2015), as a part of our group
collaboration.
Since 2016 I am on contract as an associate professor
(Contratado Doctor) at the UdG and I have supervised three doctoral Thesis (one
in progress) on glycobioloby in cancer, two with European Mention, 15 Master’s
Thesis and more than 25 Final Degree Projects. My research work has generated
two patents, one book chapter, 30 scientific publications with more than 800
citations (h-index=17) and numerous presentations in international symposiums.
At present, I am coordinator of Master’s Degree in
Molecular Biology and Biomedicine at UdG, I have two teaching merits assessment
(2012-2017/ 2018-2022); three research sexennial periods (2003-2008/ 2009-2014/
2015-2020); I am co-leading the Biochemistry of Cancer group and the research
projects: Non-invasive biomarkers for Prostate Cancer clinical risk
stratification: PSA glycoforms and multiparametric magnetic resonance imaging” funded
by La Marató TV3 and “Glicosilación alterada en cáncer de páncreas: Base para
el desarrollo de nuevos biomarcadores y dianas terapéuticas” funded by MICINN
(ref: PID2020-115686RB-I00).
Besides the regularly work with the clinical
team of the Hospital Dr.J Trueta, our team collaborates with international groups,
highlighting collaborations with Dr. R. Saldova of the NIBRT (Dublin) experts
in glycobiology; Dr. C. Reis of the IPATIMUP (Porto), experts in mucins and
glycosyltransferases, Dr. K. Konstantopoulos at the Johns Hopkins University
(Baltimore) experts in the study of cell adhesion and migration using
microfluidics technology. At national level we are closely collaborating with
Dr. P. Navarro and Dr. O. Pozo from the IMIM (Barcelona) in the area of biomarkers
discovery for pancreatic cancer and recently, with Dr. A. González from the
University of Vigo in the field of pancreatic organoids culture and Dr. A
Palazón from the CICbioGUNE for the study of the role of siglecs receptors as
immunecheck points in pancreatic cancer.
Current Position and Education:
Associate Professor at the University of Girona from 2016 (Biochemistry and Molecular Biology Unit / Department of Biology)
PhD in Biomedicine (Health Sciences) - Pompeu Fabra University (2008)
Bachelor's degree in Biology - University of Barcelona (2005)
Bachelor's degree in Biochemistry - University of Barcelona (2001)
Research Lines:
- Tumour markers: study of altered glycosylation of various serum glycoproteins as possible carcinoma tumour markers. Presently focused on pancreatic and prostate carcinomas, in particular the anomalous glycosilation of over-expressed or new-expressed seric glycoproteins in pancreatic cancer and of PSAs (prostate-specific antigens). Extensible to other glycoproteins (Proteomics and Glycomics).
- Molecular mechanisms responsible for changes in glycosylation in tumours. Studies of the expression of glycosyltransferase responsible for the biosynthesis of carbohydrate antigens associated with tumours, determination of their implication in different stages of tumour progression and of the factors that regulate its expression.
- Directed therapy against specific glycosyltransferase: screening of drugs in 2D and 3D models and live validation using drug-response biomarkers
Publications:
- Miró L, López J, Guerrero PE, Martínez-Bosch N, Manero-Rupérez N, Moreno M, Ortiz MR, Llop E, Navarro P, Peracaula R. Sialyltransferase Inhibitor Ac53FaxNeu5Ac Reverts the Malignant Phenotype of Pancreatic Cancer Cells, and Reduces Tumor Volume and Favors T-Cell Infiltrates in Mice. Cancers 14:24. 2022.
- Duran A, Guerrero PE, Ortiz MR, Pérez Del Campo D, Castro E, Garcia-Velasco A, Fort E, de Llorens R, Saldova R, Llop E, Peracaula R. Characterization of Mesothelin Glycosylation in Pancreatic Cancer: Decreased Core Fucosylated Glycoforms in Pancreatic Cancer Patients’ Sera. Biomedicines 10:8. 2022.
- Greville G, Llop E, Howard J, Madden SF, Perry AS, Peracaula R, Rudd PM, McCann A, Saldova R. 5-AZA-dC induces epigenetic changes associated with modified glycosylation of secreted glycoproteins and increased EMT and migration in chemo-sensitive cancer cells. Clin Epigenetics 13(1):34. 2021.
- Greville G, Llop E, Howard J, Madden SF, Perry AS, Peracaula R, Rudd PM, McCann A, Saldova R. 5-AZA-dC induces epigenetic changes associated with modified glycosylation of secreted glycoproteins and increased EMT and migration in chemo-sensitive cancer cells. Clin Epigenetics 13(1):34. 2021.
- Guerrero PE, Durán A, Ortiz-Duran R, Castro E, Garcia-Velasco A, Llop E, Peracaula R. Microfibril associated protein 4 (MFAP4) is a carrier of the tumor associated carbohydrate sialyl Lewis X (sLex) in pancreatic adenocarcinoma. Journal of Proteomics, 231, 104004. 2021.
- Benito Mundet, H.; Llop Escorihuela, E.; Verdaguer Planas, M.; Comas Matas, J.; Lleonart Sitjar, A.; Orts Alis, M.; Amadó Dodony, A. & Rostan Sánchez, C. MULTIDIMENSIONAL RESEARCH ON UNIVERSITY ENGAGEMENT USING A MIXED METHOD APPROACH. Educación XX1. 2021.
- Guerrero PE, Miró L, Wong BS, Massaguer A, Martínez-Bosch N, Llorens R, Navarro P, Konstantopoulos K, Llop E, Peracaula R. Knockdown of a2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion. Int J Mol sci. 21(17):6239. 2020.
- Gratacós-Mulleras A, Duran A, Asadi Shehni A, Ferrer-Baballé M, Ramírez M, Comet J, de Llorens R, Saldova R, Llop E, Peracaula R. Characterisation of the main PSA glycoforms in aggressive prostate cancer. Scientific Reports, 10:18974. 2020.
- Greville G, Llop E, Huang C, Creagh-Flynn J, Pfister S, O'Flaherty R, Madden SF, Peracaula R, Rudd PM, McCann A, Saldova R. Hypoxia Alters Epigenetic and N-Glycosylation Profiles of Ovarian and Breast Cancer Cell Lines in-vitro. Front Oncol. 10:1218. 2020.
- Llop E, E Guerrero P, Duran A, Barrabés S, Massaguer A, José Ferri M, Albiol-Quer M, de Llorens R, Peracaula R. Glycoprotein biomarkers for the detection of pancreatic ductal adenocarcinoma. World J Gastroenterol. 24(24), 2537-2554. 2018.
- Balmaña M, Duran A, Gomes C, Llop E, López-Martos R, Ortiz MR, Barrabés S, Reis CA, Peracaula R. Analysis of sialyl-Lewis x on MUC5AC and MUC1 mucins in pancreatic cancer tissues. Int. J. Biol Macromol. 112:33-45. 2018.
- Barrabés, S, Llop, E, Ferrer-Batallé, M, Ramírez, M, Aleixandre, R.N, Perry, A.S, de Llorens, R, Peracaula, R. Anlysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer. Clinica Chimica Acta 470, 97-102. 2017.
- Ferrer-Batallé M, * Llop E, Ramírez M, Aleixandre RN, Saez M, Comet J, de Llorens R, Peracaula R. Comparative Study of Blood-Based Biomarkers, a2,3-Sialic Acid PSA and PHI, for High-Risk Prostate Cancer Detection. Int J Mol Sci. 18(4). 2017.
- Barrabés S, Farina-Gomez N, Llop E, Puerta A, Diez-Masa JC, Perry A, de Llorens R, de Frutos M, Peracaula R.Comparative analysis of prostate specific antigen (PSA) by two-dimensional gel electrophoresis and capillary electrophoresis. Electrophoresis. 2017.
- Llop E, Ferrer-Batallé M, Barrabés S, Guerrero P.E, Ramírez M, Saldova R., Rudd P.M., Aleixandre R.N, Comet J, de Llorens R, Peracaula R. Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes. Theranostics. 6 (8), 1190-1204. 2016.
- Balmaña M, Giménez E, Puerta A, Llop E, Figueras J., Fort E, Sanz-Nebot V, de Bolós C, Rizzi A, Barrabés S, de Frutos M, Peracaula R. Increased a1-3 fucosylation of a-1-acid glycoprotein (AGP) in pancreatic cancer. Journal of Proteomics, 132; 144-154. 2016.
- Balmaña M, Sarrats A, Llop E, Barrabés S, Saldova R, Ferri MJ, Figueras J, Fort E, de Llorens R, Rudd PM, Peracaula R. Identification of potential pancreatic cancer sèrum markers: Increased sialyl-Lewis X on ceruloplasmin. Clin Chim Acta. 442: 56-62. 2015.
- Bassagañas S, Allende H, Cobler L, Ortiz M.R, Llop E, de Bolós C, Peracaula R. Inflammatory cytokines regulate the expression of glycosyltransferases involved in the biosynthesis of tumor-associated sialylated glycans in pancreatic cancer cell lines. Cytokine, 75, (1); 197-206. 2015.
- Pérez-Garay M, Arteta B, Llop E, Cobler L, Pagès L, Ortiz R, Ferri MJ, de Bolós C, Figueras J, de Llorens R, Vidal-Vanaclocha F, Peracaula R. a2,3-sialyltransferase ST3Gal IV promotes migration and metastasis in pancreatic adenocarcinoma cells and tends to be highly expressed in pancreatic adenocarcinoma tissues. The International Journal of Biochemistry & Cell Biology, 45(8): 1748-1757. 2013.
- Gutiérrez-Gallego R, Llop E, Bosch J, Segura J. Surface Plasmon Resonance in doping analysis. Analytical and Bioanalytical Chemistry, 401(2), 389-403. 2011.
- Mallorquí J, Llop E, de Bolós C, Gutiérrez-Gallego R, Segura J, Pascual JA. Erythropoietin purification in human plasma samples using an immunoaffinity well plate. Journal Chromatography B, 878(23), 2117-22. 2010.
- Martínez-Martínez I, Ordóñez A, Navarro-Fernández J, Pérez-Lara A, Gutiérrez-Gallego R, Giraldo R, Martínez C, Llop E, Vicente V, Corral J. Antithrombin Murcia (K241E) causing antithrombin deficiency: a role for altered glycosylation. Haematologica, 95(8), 1358-65. 2010.
- Izquierdo-Rico MJ, Jiménez-Movilla M, Llop E, Pérez-Oliva AB, Ballesta J, Gutiérrez-Gallego R, Jiménez-Cervantes C, Avilés M. Hamster Zona Pellucida Is Formed by Four Glycoproteins: ZP1, ZP2, ZP3, and ZP4. J Proteome Research, 8(2), 926-41. 2009.
- Llop E, Gutiérrez-Gallego R, Segura J, Mallorquí J, Pascual JA. Structural analysis of the glycosylation of gene-activated erythropoietin (epoetin delta, Dynepo). Anal Biochem. 383(2), 243-54. 2008.
- Ramírez-Llanelis R, Llop E, Ventura R, Segura J, Gutiérrez-Gallego R. Can glycans unveil the origin of glycoprotein hormones? – human chorionic gonadotrophin as an example. J.Mass Spectrometry, 43(7), 936-48. 2008.
- Llop E, Gutiérrez-Gallego R, Belalcazar V, Gerwig GJ, Kamerling JP, Segura J, Pascual JA. Evaluation of protein N-glycosylation in 2-DE: Erythropoietin as a study case. Proteomics, 7(23), 4278-91. 2007.
- Belalcazar V, Gutiérrez-Gallego R, Llop E, Segura J, Pascual JA. Assessing the instability of the isoelectric focusing patterns of erythropoietin in urine. Electrophoresis, 27(22), 4387-95. 2006.
- Pascual JA, Belalcazar V, de Bolós C, Gutiérrez-Gallego R, Llop E, Segura J. Recombinant erythropoietin and analogues: a challenge for doping control. Therapeutic Drug Monitoring, 26(2), 175-79. 2004.