Fernando Martinez

Fernando Martinez Estrada

Lecturer in Innate Immunology



2016 Lecturer in Immunology, Department of Biochemical Sciences, University of Surrey, Guildford, UK & Honorary Senior Research Associate, Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology, NDORMS, University of Oxford.

2012-2016 Senior research associate, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford.

2006-2012 Postdoctoral researcher, Sir William Dunn School of Pathology, University of Oxford, UK.

2000-2006 Postgraduate and PhD student, University of Milan, Italy.

Research interests

I am originally from Havana,Cuba, where I graduated as a Biochemist to then pursue a doctorate in Molecular Medicine and Immunology in Milan,Italy; I then joined Oxford University.

My main objectives in science are to understand how macrophages participate in disease pathogenesis and to identify new avenues to interfere with their deleterious properties. Macrophages are present in all tissues, numerous, and their role in inflammation is primarily controlled by modulation of their gene and protein repertoire. The transcriptome of macrophages holds the key to the fundamental question in macrophage pathobiology and inflammatory medicine: how to inactivate and reprogramme the macrophage.

My areas of expertise are macrophage cellular and systems biology (isolation-culture, gene and proteomic signatures, microarrays, proteomics, functional analysis), regulation of macrophage activation, and modern pathology. I use techniques to complement my transcriptome work, including conventional histological techniques, and modern developments such as multiple immunofluorescence histology, multiple FACS staining and Cytof. The application of the knowledge that I derive with my tools, allows reinterpretation of conventional paradigms and proposals of new ways of understanding disease and potential treatments.

My publications


van de Garde MDB, Martinez Estrada F, Melgert BN, Hylkema MN, Jonkers RE, Hamann J (2014) Chronic Exposure to Glucocorticoids Shapes Gene Expression and Modulates Innate and Adaptive Activation Pathways in Macrophages with Distinct Changes in Leukocyte Attraction, Journal of Immunology 192 pp. 1196-1208 American Association of Immunologists
Glucocorticoids (GCs) have been used for more than 50 y as immunosuppressive drugs, yet their efficacy in macrophage-dominated disorders, such as chronic obstructive pulmonary disease, is debated. Little is known how long-term GC treatment affects macrophage responses in inflammatory conditions. In this study, we compared the transcriptome of human macrophages, matured in the presence or absence of fluticasone propionate (FP), and their ability to initiate or sustain classical activation, mimicked using acute LPS and chronic IFN-³ stimulation, respectively. We identified macrophage gene expression networks, modulated by FP long-term exposure, and specific patterns of IFN-³? and LPS-induced genes that were resistant, inhibited, or exacerbated by FP. Results suggest that long-term treatment with GCs weakens adaptive immune signature components of IFN-³ and LPS gene profiles by downmodulating MHC class II and costimulatory molecules, but strengthens innate signature components by maintaining and increasing expression of chemokines involved in phagocyte attraction. In a mouse model of chronic obstructive pulmonary disease, GC treatment induced higher chemokine levels, and this correlated with enhanced recruitment of leukocytes. Thus, GCs do not generally suppress macrophage effector functions, but they cause a shift in the innate?adaptive balance of the immune response, with distinct changes in the chemokine?chemokine receptor network.
Dakin SG, Martinez Estrada F, Yapp C, Wells G, Oppermann U, Dean BJF, Smith RDJ, Wheway K, Watkins B, Roche L, Carr AJ (2015) Inflammation activation and resolution in human tendon disease, Science Translational Medicine 7 (311) pp. 311ra173-311ra173 American Association for the Advancement of Science
Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced disease, and inflammation was characterized through activation of pathways mediated by interferon (IFN), nuclear factor ºB (NF-ºB), glucocorticoid receptor, and signal transducer and activator of transcription 6 (STAT-6). Inflammation signatures revealed expression of genes and proteins induced by IFN and NF-ºB in early-stage disease and genes and proteins induced by STAT-6 and glucocorticoid receptor activation in advanced-stage disease. The proresolving proteins FPR2/ALX and ChemR23 were increased in early-stage disease compared to intermediate- to advanced-stage disease. Patients who were pain-free after treatment had tendons with increased expression of CD206 and ALOX15 mRNA compared to tendons from patients who continued to experience pain after treatment, suggesting that these genes and their pathways may moderate tendon pain. Stromal cells from diseased tendons cultured in vitro showed increased expression of NF-ºB and IFN target genes after treatment with lipopolysaccharide or IFN³ compared to stromal cells derived from healthy tendons. We identified 15-epi lipoxin A4, a stable lipoxin isoform derived from aspirin treatment, as potentially beneficial in the resolution of tendon inflammation.