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个人简介

Role Head of School, Biomedical and Healthcare Sciences Qualifications BSc Bristol Polytechnic, Upper second class, Applied Biological sciences, 1984. PhD University of Bristol, Department of Biochemistry, 1989. PGCertHE UWE, Bristol, 2001.

研究领域

1. Free fetal DNA (ffDNA) in maternal plasma (Dr Tracey Madgett, Kelly Sillence, Hannah Thompson) ffDNA represents the greatest potential for delivering routine non-invasive prenatal diagnosis, and especially coupled with next-generation sequencing (NGS) technologies could easily become the norm for the diagnosis of aneuploidy. Unfortunately NGS technology presently is prohibitively expensive, and we have developed methods for the enrichment of fetal DNA and depletion of maternal DNA in maternal plasma samples. The study is set to exploit the digital PCR platform we have just acquired within the Plymouth post-genomics Centre, which is due to open in November 2011. The methods involve relatively straightforward manipulations of the PCR procedure to inhibit the amplification of maternal DNA, and in one assay to actively destroy it. The work is currently funded by the NIHR, and is in collaboration with Prof Lyn Chitty (ICH/UCL/GOSH). 2. Analysis of fetal cells in maternal blood (Dr Michele Kiernan) Despite the huge advances in the study of ffDNA (described above) there are distinct advantages in being able to work with single purified fetal cells. Based on our previous work, we are isolating fetal erythroblasts using our FACSAria 2 flow cytometer, and investigation the transcriptome using next-generation sequencing. With this we hope to identify fetal erythroblast specific biomarkers to enable their more efficient isolation from maternal blood samples. We consider the lack of suitable biomarkers of erythroid cells to be a key factor in the ineffectiveness of fetal cell isolation methodologies in the past. 3. Molecular Investigation of Mechanisms of red cell turnover (Dr Kris Jeremy) Continuing a project started in the 2000s, we are studying the role of the red cell form of CD47 and how huge numbers of effete red cells are removed from the circulation on a daily basis. We are using proteomics techniques to achieve this and are using normal red cells and CD47 deficient cells. Post-translational modification (PTM), involving PKA and PKC phosphorylation of red cell membrane components are critical in this process, and we are studying the precise molecular pathway involved. We have recently obtained a Thermo orbitrap Velos elite mass spectrometer (the first such instrument in the UK) to investigate the nature of the PTMs involved. The study is in collaboration with Prof Rob Barker (University of Aberdeen) as is funded by the Wellcome trust. 4. New Serum Screening biomarkers for aneuploidy (Kelly Sillence) We have identified a significant number of biomarkers using CVS samples from Down and non-Down mothers by transcriptomics, and by previous proteomics studies (see Heywood et al., (2011) in publications list). We are validating these markers after raising monoclonal antibodies to them. Many Down-specific changes involve PTMs and we will use our new Orbitrap velos mass spectrometer to identify their molecular nature- knowing precisely which protein species is involved. Study funded by the Fetal medicine Foundation in collaboration with Prof Kypros Nicolaides and Dr Ranjit Akolekar 5. New roles for the CD47 glycoprotein (Dr Kris Jeremy) A study in collaboration with Prof Oliver Hanemann (PCMD), we are investigating the binding partners of CD47 in neural tissue, and then using CD47 ligands as potential new therapeutic agents against brain tumours, especially Schannoma.

近期论文

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Sillence KA, Roberts LA, Hollands HJ, Thompson HP, Kiernan M, Madgett TE, Welch CR & Avent ND 2015 'Fetal Sex and RHD Genotyping with Digital PCR Demonstrates Greater Sensitivity than Real-time PCR' CLINICAL CHEMISTRY 61, (11) 1399-1407 Author Site , DOI PEARL Li B, Pan G, Avent ND, Lowry RB, Madgett TE & Waines PL 2015 'Graphene electrode modified with electrochemically reduced graphene oxide for label-free DNA detection' BIOSENSORS & BIOELECTRONICS 72, 313-319 Author Site , DOI PEARL Li B, Pan G, Jamil NY, Al Taan L, Awan S & Avent N 2015 'Shielding technique for deposition of Au electrical contacts on graphene by sputtering' JOURNAL OF VACUUM SCIENCE & TECHNOLOGY A 33, (3) Author Site , DOI PEARL Alrammah H, Woldie WA, Avent N & Jackson SK 2014 'Overexpression of lysophosphatidylcholine acyltransferase 2 (LPCAT2) up-regulated LPS-induced responses in a murine macrophage' IMMUNOLOGY 143, 104-105 Author Site Avent ND 2014 'Prenatal testing for hemolytic disease of the newborn and fetal neonatal alloimmune thrombocytopenia - current status' Expert Rev Hematol 7, (6) 741-745 Author Site , DOI Avent ND 2013 'Glycophorin C ligation: another biochemical pathway in red blood cell senescence?' Transfusion 53, (10) Author Site , DOI Avent ND 2013 'Maternal plasma biomarkers for down syndrome: present and future' Drugs Today (Barc) 49, (2) 145-152 Author Site , DOI Sillence KA, Madgett TE, Roberts LA, Overton TG & Avent ND 2013 'Non-Invasive Screening Tools for Down's Syndrome: A Review' Diagnostics (Basel, Switzerland) 3, (2) 291-314 , DOI Haer-Wigman L, Veldhuisen B, Jonkers R, Lodén M, Madgett TE, Avent ND, de Haas M & van der Schoot CE 2013 'RHD and RHCE variant and zygosity genotyping via multiplex ligation-dependent probe amplification' Transfusion 53, (7) 1559-1574 Author Site , DOI Heywood W, Mills K, Wang D, Hogg J, Madgett TE, Avent ND & Chitty LS 2012 'Identification of new biomarkers for Down's syndrome in maternal plasma' J Proteomics 75, (9) 2621-2628 Author Site , DOI

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