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Dr Paul Simons


Personal Profile

Name: Paul Simons Email: p.simons@ucl.ac.uk
Title: Dr Tel: 020 7830 2415
Department: Inflammation Fax:
Position: Reader in Experimental Genetics and Molecular Medicine Address: Royal Free Campus, Rowland Hill Street, London, NW3 2PF
Research Domain: Ageing, Basic Life Sciences, Biomedical Imaging (Frontier Disciplines), Cardiometabolic Science, Genetics (Frontier Disciplines), Infection, Immunology & Inflammation, Neuroscience, Personalised Medicine, Reproduction & Development, Stem Cells & Regenerative Medicine (Frontier Disciplines) Web Page:  


Research Description

Research Activities

Alternative splicing of APOB and GHR


Gene- and oligonucleotide-based therapies

Models of Neurodegenerative Disease

Education Description

UCL Collaborators

Prof Sir Mark Pepys; Dr Aris Tagalakis; Dr Bernard Khoo; Dr Mark Cooper; Prof Jim Owen; Prof Rhona Mirsky; Dr Alun Coker; Prof Amit Nathwani; Prof Justin Hsuan

External Collaborators



    • Killick R, Hardy J, Simons JP (2015). Reducing beta-Amyloid by Inhibition of BACE1: How Low Should You Go?. BIOLOGICAL PSYCHIATRY, 77(8), 683 - 684.


    • Cooper JM, Wiklander PB, Nordin JZ, Al-Shawi R, Wood MJ, Vithlani M, Schapira AH, Simons JP, El-Andaloussi S, Alvarez-Erviti L (2014). Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice.. Mov Disord, 29(12), 1476 - 1485. doi:10.1002/mds.25978
    • Killick R, Ribe EM, Al-Shawi R, Malik B, Hooper C, Fernandes C, Dobson R, Nolan PM, Lourdusamy A, Furney S, Lin K, Breen G, Wroe R, To AW, Leroy K, Causevic M, Usardi A, Robinson M, Noble W, Williamson R, Lunnon K, Kellie S, Reynolds CH, Bazenet C, Hodges A, Brion JP, Stephenson J, Simons JP, Lovestone S (2014). Clusterin regulates β-amyloid toxicity via Dickkopf-1-driven induction of the wnt-PCP-JNK pathway.. Mol Psychiatry, 19(1), 88 - 98. doi:10.1038/mp.2012.163
    • Simons JP, Loeffler JM, Al-Shawi R, Ellmerich S, Hutchinson WL, Tennent GA, Petrie A, Raynes JG, de Souza JB, Lawrence RA, Read KD, Pepys MB (2014). C-reactive protein is essential for innate resistance to pneumococcal infection.. Immunology, 142(3), 414 - 420. doi:10.1111/imm.12266
    • Halabelian L, Ricagno S, Giorgetti S, Santambrogio C, Barbiroli A, Pellegrino S, Achour A, Grandori R, Marchese L, Raimondi S, Mangione PP, Esposito G, Al-Shawi R, Simons JP, Speck I, Stoppini M, Bolognesi M, Bellotti V (2014). Class I major histocompatibility complex, the trojan horse for secretion of amyloidogenic β2-microglobulin.. J Biol Chem, 289(6), 3318 - 3327. doi:10.1074/jbc.M113.524157


    • Simons JP, Al-Shawi R, Ellmerich S, Speck I, Aslam S, Hutchinson WL, Mangione PP, Disterer P, Gilbertson JA, Hunt T, Millar DJ, Minogue S, Bodin K, Pepys MB, Hawkins PN (2013). Pathogenetic mechanisms of amyloid A amyloidosis.. Proc Natl Acad Sci U S A, 110(40), 16115 - 16120. doi:10.1073/pnas.1306621110
    • Disterer P, Simons JP, Owen JS, Khoo B (2013). APO-skip splice-switching oligonucleotides to treat familial hypercholesterolemia.
    • Disterer P, Al-Shawi R, Ellmerich S, Waddington SN, Owen JS, Simons JP, Khoo B (2013). Exon Skipping of Hepatic APOB pre-mRNA with Splice-switching Oligonucleotides Reduces LDL Cholesterol In Vivo. Molecular Therapy, , - . doi:10.1038/mt.2012.264
    • Campbell-Washburn AE, Price AN, Ellmerich S, Simons JP, Al-Shawi R, Kalber TL, Ghatrora R, Hawkins PN, Moon JC, Ordidge RJ, Pepys MB, Lythgoe MF (2013). Monitoring systemic amyloidosis using MRI measurements of the extracellular volume fraction.. Amyloid, 20(2), 93 - 98. doi:10.3109/13506129.2013.787984


    • Disterer P, Papaioannou I, Evans VC, Simons JP, Owen JS (2012). Oligonucleotide-mediated gene editing is underestimated in cells expressing mutated green fluorescent protein and is positively associated with target protein expression.. J Gene Med, 14(2), 109 - 119. doi:10.1002/jgm.1639
    • Papaioannou I, Simons JP, Owen JS (2012). Targeted In Situ Gene Correction of Dysfunctional APOE Alleles to Produce Atheroprotective Plasma ApoE3 Protein.. Cardiol Res Pract, 2012, 148796 - . doi:10.1155/2012/148796
    • Papaioannou I, Simons JP, Owen JS (2012). Oligonucleotide-directed gene-editing technology: mechanisms and future prospects.. Expert Opin Biol Ther, 12(3), 329 - 342. doi:10.1517/14712598.2012.660522


    • Cleeter M, Houlden H, Simons P, Al-Shawi R, Stevanin G, Durr A, Hsuan J, Warner TT (2011). Screening for mutations in the phosphatidylinositol 4-kinase 2-alpha gene in autosomal recessive hereditary spastic paraplegia. Amyotrophic Lateral Sclerosis, 12, 148 - 149.
    • Campbell AE, Price AN, Ellmerich S, Simons P, Al-Shawi R, Hawkins PN, Ordidge RJ, Pepys MB, Moon JC, Lythgoe MF (2011). Equilibrium contrast CMR for the detection of amyloidosis in mice. doi:10.1186/1532-429X-13-S1-O60
    • Evans VC, Graham IR, Athanasopoulos T, Galley DJ, Jackson CL, Simons JP, Dickson G, Owen JS (2011). Adeno-associated virus serotypes 7 and 8 outperform serotype 9 in expressing atheroprotective human apoE3 from mouse skeletal muscle.. Metabolism, 60(4), 491 - 498. doi:10.1016/j.metabol.2010.04.015
    • Disterer P, Simons JP, Owen J, Khoo B (2011). Reducing LDL cholesterol with exon-skipping antisense oligonucleotides.


    • Simons P, Al-Shawi R, Ellmerich S, Slamova I, Bodin K, Minogue S, Pepys MB, Hawkins PN (2010). Controllable expression of SAA in transgenic mice: a refined model of systemic amyloidosis.


    • Simons JP, Al-Shawi R, Minogue S, Waugh MG, Wiedemann C, Evangelou S, Loesch S, Sihra TS, King R, Warner TT, Hsuan JJ (2009). Loss of phosphatidylinositol 4-kinase 2-alpha activity causes late onset degeneration of spinal cord axons. Proceedings of the National Academy of Sciences of the United States of America, 106(28), 11535 - 11539. doi:10.1073/pnas.0903011106
    • Woodhoo A, Alonso MB, Droggiti A, Turmaine M, D'Antonio M, Parkinson DB, Wilton DK, Al-Shawi , R , Simons P, Shen J, Guillemot F, Radtke F, Meijer D, Feltri ML, Wrabetz L, Mirsky R, Jessen KR (2009). Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity.. Nature Neuroscience, 12, 839 - 847. doi:10.1038/nn.2323
    • Kimura A, Stevenson PL, Carter RN, MacColl G, French KL, Simons JP, Al-Shawi R, Kelly V, Chapman KE, Holmes MC (2009). Overexpression of 5-HT2C receptors in forebrain leads to elevated anxiety and hypoactivity.. European Journal of Neuroscience, 30, 299 - 306. doi:10.1111/j.1460-9568.2009.06831.x
    • Disterer P, Simons JP, Owen JS (2009). Validation of oligonucleotide-mediated gene editing. Gene Therapy, 16(6), 824 - 826.


    • Evans V, Foster H, Graham IR, Foster K, Athanasopoulos T, Simons JP, Dickson G, Owen JS (2008). Human apolipoprotein E expression from mouse skeletal muscle by electrotransfer of nonviral DNA (plasmid) and pseudotyped recombinant adeno-associated virus (AAV2/7).. Human Gene Therapy, 19(6), 569 - 578. doi:10.1089/hum.2007.169
    • Al-Shawi R, Hafner A OJ, Chun S RS, Thrasivoulou C, Lovestone S, Killick R, Simons P, Cowen T (2008). Neurotoxic and neurotrophic roles of proNGF and the receptor sortilin in the adult and ageing nervous system.. European Journal of Neuroscience, 27(8), 2103 - 2114.
    • Osman E, Evans V, Graham IR, Athanasopoulos T, McIntosh J, Nathwani AC, Simons JP, Dickson GO, J S (2008). Preliminary evaluation of a self-complementary AAV2/8 vector for hepatic gene transfer of human apoE3 to inhibit atherosclerotic lesion development in apoE-deficient mice. Atherosclerosis, 204(1), 121 - 126. doi:10.1016/j.atherosclerosis.2008.08.043


    • Al-Shawi R, Hafner A CS, Raza S CK, Thrasivoulou C SP, Cowen T (2007). ProNGF, sortilin, and age-related neurodegeneration.. Annals of the New York Academy of Sciences, 1119, 208 - 215. doi:10.1196/annals.1404.024
    • Disterer P, Papaioannou I, Simons JP, Owen JS (2007). High and stable genomic sequence modification with oligonucleotide-mediated gene editing.
    • Ates K, Yang SY, Orrell RW, Sinanan AC, Simons P, Solomon A, Beech S, Goldspink G, Lewis MP (2007). The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and normal muscle.. FEBS Letters, 581(14), 2727 - 2732.


    • Zeng Z, Sharpe CR, Simons JP, Gorecki DC (2006). The expression and alternative splicing of alpha-neurexins during Xenopus development. International Journal of Developmental Biology, 50(1), 39 - 46.
    • Evans V, Graham I, Foster H, Foster K, Simons JP, Dickson G, Owen JS (2006). Intramuscular electrotransfer of a plasmid expressing apolipoprotein E (Apo-E) to reverse hyperlipidaemia in Apo-E-deficient mice.


    • Tagalakis A, Owen J, Simons JP (2005). Lack of RNA-DNA oligonucleotide (chimeraplast) mutagenic activity in mouse embryos. Molecular Reproduction and Development, 71(2), 140 - 144. doi:10.1002/mrd.20250
    • Tagalakis AD, Dickson G, Owen JS, Simons JP (2005). Correction of the neuropathogenic human apolipoprotein E4 (APOE4) gene to APOE3 in vitro using synthetic RNA/DNA oligonucleotides (chimeraplasts).. Journal of Molecular Neuroscience, 25, 95 - 104.


    • Lien CF, Vlachouli C, Blake DJ, Simons JP, Gorecki DC (2004). Differential spatio-temporal expression of alpha-dystrobrevin-1 during mouse development. Gene Expression Patterns, 4(5), 583 - 593. doi:10.1016/j.modgep.2004.01.015


    • Abdulrazzak H, Noro N, Simons JP, Goldspink G, Barnard EA, Gorecki DC (2001). Structural diversity despite strong evolutionary conservation in the 5 '-untranslated region of the P-type dystrophin transcript. Molecular and Cellular Neuroscience, 17(3), 500 - 513. doi:10.1006/mcne.2000.0950
    • Al-Shawi R, Ashton SV, Underwood C, Simons JP (2001). Expression of the Ror1 and Ror2 receptor tyrosine kinase genes during mouse development. Development, Genes and Evolution, 211(4), 161 - 171. doi:10.1007/s004270100140


    • Gorecki DC, Szklarczyk A, Lukasiuk K, Kaczmarek L, Simons JP (1999). Differential seizure-induced and developmental changes of neurexin expression. Molecular and Cellular Neuroscience, 13(3), 218 - 227.
    • Gorecki DC, Simons JP (1999). The dangers of DNA vaccination. Nature Medicine, 5(2), 126 - .


    • Partridge J, Wallace DF, Robertson A, Fox MF, Simons JP, Dooley JS, Walker AP (1998). Cloning and molecular characterization of a cross-homologous zinc finger locus ZNF204.. Genomics, 50, 116 - 118.


    • Henderson G, Simons JP (1997). Processing of DNA prior to illegitimate recombination in mouse cells.. Molecular and Cellular Biology, 17(7), 3779 - 3785.
    • Archibald AL, Clark AJ, Harris S, McClenaghan M, Simons JP, Whitelaw CBA (1997). Genetic construct of which protein coding DNA comprises introns and is designed for protein production in transgenic animals.


    • Burgoyne RD, Handel SE, Sudlow AW, Turner MD, Kumar S, Simons JP, Blatchford DRAW, C J (1995). The secretory pathway for milk protein secretion and its regulation.. In Wilde CJ, Peaker M, Knight CH (Ed.), Intercellular Signalling in the Mammary Gland (pp. 253 - 263). : .


    • Kumar S, Clarke AR, Hooper ML, Horne DS, Law AJ, Leaver J, Springbett A, Stevenson E, Simons JP (1994). Milk composition and lactation of beta-casein-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 91(13), 6138 - 6142.


    • Clark AJ, Archibald AL, McClenaghan M, Simons JP, Wallace R, Whitelaw CB (1993). Enhancing the efficiency of transgene expression.. Philos Trans R Soc Lond B Biol Sci, 339, 225 - 232.
    • Simons JP, Ali S, Archibald AL, Brown P, Harris S, McClenaghan M, Whitelaw CBA, Wilmut I, Clark AJ (1993). Genetic Manipulation in Livestock Improvement. In Beh KJ (Ed.), Animal Health and Production for the 21st Century (pp. 15 - 25). : CSIRO Publications.
    • Hall J, Ali S, Surani MA, Hazlewood GP, Clark AJ, Simons JP, Hirst BHAG, H (1993). Manipulation of the repertoire of digestive enzymes secreted into the gastrointestinal tract of transgenic mice.. Bio/Technology, 11, 376 - 379. doi:10.1038/nbt0393-376
    • Kumar SS, JP (1993). The effects of terminal heterologies on gene targeting by insertion vectors in embryonic stem cells.. Nucleic Acids Research, 21, 1541 - 1548.


    • Wilde CJ, Clark AJ, Kerr MA, Knight CH, McClenaghan M, Simons JP (1992). Mammary development and milk secretion in transgenic mice expressing the sheep β-lactoglobulin gene.. Biochemical Journal, 284, 717 - 720.
    • Clark AJ, Simons JP, Wilmut I (1992). Germ line manipulation: applications in agriculture and biotechnology.. In Grosveld F, Kollias G (Ed.), Transgenic Animals (pp. 247 - 270). : .
    • Clark AJ, Cowper A, Wallace R, Wright G, Simons JP (1992). Rescuing transgene expression by co-integration.. Bio/Technology, 10, 1450 - 1454. doi:10.1038/nbt1192-1450
    • Whitelaw CBA, Harris S, McClenaghan M, Simons JP, Clark AJ (1992). Position independent expression of the ovine β-lactoglobulin gene in transgenic mice.. Biochemical Journal, 286, 31 - 39.
    • Wilmut I, Haley CS, Simons JP, Webb R (1992). The potential role of molecular genetic manipulation in the improvement of reproductive performance.. , 45, 157 - 173.


    • Harris S, McClenaghan M, Simons JP, Ali S, Clark AJ (1991). Developmental regulation of the sheep β-lactoglobulin gene in the mammary gland of transgenic mice.. Developmental Genetics, 12, 299 - 307.
    • Wright G, Carver A, Cottom D, Reeves D, Scott A, Simons P, Wilmut I, Garner IAC, A (1991). Livestock as bioreactors: high level expression of active human α1-antitrypsin in the milk of transgenic sheep.. Bio/Technology, 9, 830 - 834.
    • McClenaghan M, Archibald AL, Harris S, Simons JP, Whitelaw CBA, Wilmut IC, A J (1991). Production of human α1-antitrypsin in the milk of transgenic sheep and mice: targeting expression of cDNA sequences to the mammary gland.. Animal Biotechnology, 2, 161 - 176.
    • Wilmut I, Archibald AL, McClenaghan M, Simons JP, Whitelaw B, and Clark AJ (1991). Production of pharmaceutical proteins in milk.. Experientia, 47, 905 - 912.
    • Whitelaw CBA, Archibald AL, Harris S, McClenaghan M, Simons JP, Clark AJ (1991). Targeting expression to the mammary gland: intronic sequences can enhance the efficiency of gene expression in transgenic mice.. Transgenic Research, 1, 3 - 13.


    • Ali S, McClenaghan M, Simons JPAC, A J (1990). Characterisation of the alleles encoding ovine β-lactoglobulins A and B.. Gene, 91, 201 - 207.
    • Harris S, McClenaghan M, Simons JP, Ali S, Clark AJ (1990). Gene expression in the mammary gland.. J. Reprod. Fertil. Suppl., 88, 707 - 715.
    • Archibald AL, McClenaghan M, Hornsey V, Simons JPAC, A J (1990). High-level expression of biologically active human α11 antitrypsin in the milk of transgenic mice.. Proceedings of the National Academy of Sciences of the United States of America, 87, 5178 - 5182.
    • Wilmut I, Archibald AL, Harris S, McClenaghan M, Simons JP, Whitelaw CBAC, A J (1990). Methods of gene transfer and their potential use to modify milk composition.. Theriogenology, 33, 113 - 123. doi:10.1016/0093-691X(90)90602-P
    • Wilmut I, Archibald AL, Harris S, McClenaghan M, Simons JP, Whitelaw CBAC, A J (1990). Modification of Milk Composition.. J. Reprod. Fertil. Suppl., 43, 135 - 146.


    • Clark AJ, Bessos H, Bishop JO, Brown P, Harris S, Lathe R, McClenaghan M, Prowse C, Simons JP, Whitelaw CBAAW, I (1989). Expression of human anti-hemophilic factor IX in the milk of transgenic sheep.. Bio/Technology, 7, 487 - 492.
    • Simons JP (1989). Modification of milk by gene transfer. In Barth CA, Schlimme E (Ed.), Milk proteins: Nutritional, clinical, functional and technological aspects. (pp. 124 - 132). : .
    • Clark AJ, Ali S, Archibald AL, Bessos H, Brown P, Harris S, McClenaghan M, Prowse C, Simons JP, Whitelaw CBA, Wilmut I (1989). The molecular manipulation of milk composition.. Genome, 31, 950 - 955.


    • Wilmut I, Clark , A J, Simons , J P (1988). A revolution in animal breeding.. New Scientist, 119, 56 - 59.
    • Al-Shawi R, Burke J, Jones CT, Simons JPAB, J O (1988). A Mup promoter-thymidine kinase reporter gene shows relaxed tissue-specific expression and confers male sterility upon transgenic mice.. Molecular and Cellular Biology, 8, 4821 - 4828.
    • Simons JP, Wilmut I, Clark AJ, Bishop JOAL, R (1988). Gene transfer into sheep.. Bio/Technology, 6, 179 - 183.


    • Clark AJ, Simons P, Wilmut IAL, R (1987). Pharmaceuticals from transgenic livestock.. Trends in Biotechnology, 5, 20 - 24. doi:10.1016/0167-7799(87)90076-X
    • Simons JP, Land RB (1987). Transgenic Livestock.. J Reprod Fertil Suppl., 34, 237 - 250.
    • Simons JP, McClenaghan MC, A J (1987). Alteration of the quality of milk by expression of sheep β-lactoglobulin in transgenic mice. Nature, 328, 530 - 532.


    • Lathe R, Clark AJ, Archibald AL, Bishop JO, Simons P, Wilmut I (1986). Novel products from livestock.. In Smith C, King JWB, McKay JC (Ed.), Exploiting New Technologies in animal breeding: Genetic developments. (pp. 91 - 102). : Oxford University Press.


    • Jeffreys AJ, Wilson V, Wood D, Simons JP, Kay RM, Williams JG (1980). Linkage of α- and β-globin genes in X. laevis and gene duplication by tetraploidization.. Cell, 21, 555 - 564.

    • Khoo B, Simons JP, Owen JS, Disterer P (). Antisense Oligonucleotides.