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Biomarkers of oxygenation, exposure and risk

Oxygenation: Erythropoiesis and Blood Transfusions

The lab focuses on detection and monitoring of Erythropoiesis Stimulating Agents (ESAs). In this research line led by Dr. José A. Pascual, the group is one of the world leaders in strategies differentiating between recombinant preparations of erythropoietin (rEPO) or analogues (e.g. darbepoetin, pegserpoetin, etc.) and the endogenously produced hormone (EPO). Research performed by the group in the structural elucidation of the glycans of those recombinant glycoproteins showed differences with respect to those present in humans. Reports of autoimmune problems caused by the chronic administration of those pharmaceutical preparations suggest that glycosylation may play a critical role from the safety point of view. Particular attention has been paid to the detection of the presence of N-glycolyl-neuraminic acid (Neu5Gc), a non-human monosaccharide identified in all glycosylated proteins being produced in non-human cells (CHO, BHK, etc.) and antibodies raised against it.

Currently, efforts are being made to develop instrumental (basically MS) methodologies to detect neu5Gc-containing glycopeptides from rEPO or analogues at the very low levels present in biological fluids. Those methodologies would provide, for the first time, unambiguous evidence of the exogenous origin of circulating EPO.

Dr. José A. Pascual is one of the co-authors of the official WADA’s Technical Document on analysis of EPO and analogues used globally for these antidoping determinations and the Technical Document on mass spectrometric identification criteria amongst others.

The Group has carried out multiple research projects in developing methods to detect the abuse of blood transfusions in sportsmen. The approach is based on the detection of markers of red blood cell aging due to storage of blood in transfused subjects studying changes in erythrocyte membranes occurring along their storage. Dr. José A. Pascual initiated a line in cooperation with Dr. Peter Kristensen from the Department of Engineering at the University of Aarhus, Denmark, a leading group in recombinant antibody development and phage display technologies, aiming at developing antibodies against non-human EPO antigens and also against specific markers of ex-vivo erythrocyte aging which are not present in regular circulating erythrocytes.

Biomarkers of Drug Abuse Exposure: Nicotine and Alcohol

Two of the more widespread used addictive substances are nicotine and alcohol. For many years the BASRG has been working on problems associated with the analysis of non-conventional matrices (i.e. hair, teeth, oral fluids, sweat, etc.).

Through this expertise, the BASRG have been cooperating with other groups working on the health issues related with the environmental exposure to tobacco smoke (ETS). This cooperation has extended to the analysis of metabolites of nicotine in saliva or the analysis of nicotine in hair. Dr. José A. Pascual has led a research line working together with Dr. Esteve Fernández from the Service of Cancer prevention and Control of the Catalan Institute of Oncology and Dr. José María Martínez Sanchez from the Department of Basic Science, Shool of Medicine and Health Sciences, International University of Catalonia aiming at studying the impact of the ‘anti-tobacco’ Spanish law(s) on public exposure to tobacco smoke, smoking habits, and lately, exposure to second hand smoke and tobacco specific carcinogens (i.e. TSNAs) and e-cigarette use. This research has had a great outcome to evidence the impact of the Spanish Tobacco legislation and policies to follow thereafter