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Dr Pablo Cespedes is a Translational Research Fellow in the Kennedy Institute of Rheumatology (Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences). Here he discusses his project and benefits he has drawn from his experience as an Oxford-Celgene Fellow.

Pablo Cespedes

What is your research background?

I started my researcher career in virology, microbiology and molecular genetics, and then moved quickly to immunology. My Doctor in Science degree thesis was focused in studying how the Paramyxoviridae family members human metapneumovirus (hMPV) and human respiratory syncytial virus (hRSV) interfere with the T cell priming function of dendritic cells (DC). DC are master orchestrators of adaptive immunity and our hypothesis was that viral virulence factors were interfering with the physical communication between DC and T cells. One beautiful aspect of the way these cells communicate is that they engage in a tight dance we commonly refer to as the Immunological Synapse, where they exchange a variety of signals needed for both cells to survive and activate. We found, however, that when DC are infected with hMPV or hRSV, they lose the capacity to activate T cells and the reason behind this behaviour was that the viral nucleoprotein was interfering with the recognition of the antigen by T cells. This work was done in a collaboration between professors Alexis Kalergis, Susan Bueno and Michael Dustin.      

What are you researching now?

Currently, I am investigating the Immunological Synapse from a different angle. This time I am focusing on understanding how the post-translational modification known as citrullination affects T cell or B cell activation. Citrullination is an important enzymatic process involved in both the modification of the transcriptional response of T cells and the modification of synaptic ligands, most importantly the peptide-MHC complex (also known as the T cell antigen). Understanding how citrullination influences the formation of self-reactive immune synapses is central to unravel potential therapeutic targets and to understand how pathology (disease) progresses over time. The latter is also important to identify potential T/B cell phenotypes (or signatures) related with prognosis and either the initiation or maintenance of the disease over time. Identifying disease signatures is relevant for patient segmentation in clinical trial design and required step for the development of personalised therapies.

What has your experience of this Fellowship been like?

So far has been a very nurturing experience. We have dinners and yearly meetings and travel expenses for the continuous interaction with our company partners. This has allowed us to constantly assess and adapt our scientific questions to state of the art technologies and the ongoing scientific literature. Also, our meetings foster collaboration between Celgene fellows and groups within the University of Oxford. 

What are your aspirations for the future of this research?

For me being awarded a Oxford-Celgene fellowship has been a great opportunity to pave my road to independence. In the future I would like to study factors influencing pathological immunological synapses in autoimmunity and infectious diseases. Hence, this fellowship is the best way move forward in the field.  As in autoimmunity, infections have as a common denominator the establishment of an inflammatory milieu that promotes several post-translational modifications, including citrullination and carbamylation. These may affect several aspects of the adaptive immunity ranging from antigen recognition to protein-protein interaction at the synapse, including pathogens' virulence factors. I expect developing an unique research line I can continue in the future while keeping my collaborations in Oxford and abroad.  

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