Dr Adrian Higgingbottom
Neuroscience, School of Medicine and Population Health
Senior Scientific Officer
a.higginbottom@sheffield.ac.uk
+44 114 222 2253
+44 114 222 2253
Sheffield Institute for Translational Neuroscience (SITraN)
Full contact details
Dr Adrian Higgingbottom
Neuroscience, School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
Neuroscience, School of Medicine and Population Health
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
- Publications
-
Journal articles
- A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins. Science Translational Medicine, 15(685).
- Prospects for gene replacement therapies in amyotrophic lateral sclerosis. Nature Reviews Neurology, 19(1), 39-52.
- Loss of TMEM106B exacerbates C9ALS/FTD DPR pathology by disrupting autophagosome maturation. Frontiers in Cellular Neuroscience, 16.
- SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction. Human Molecular Genetics. View this article in WRRO
- Spatiotemporal Proteomic Analysis of Stress Granule Disassembly Using APEX Reveals Regulation by SUMOylation and Links to ALS Pathogenesis. Molecular Cell, 80(5), 876-891.e6.
- Oligodendrocyte pathology exceeds axonal pathology in white matter in human amyotrophic lateral sclerosis. The Journal of Pathology. View this article in WRRO
- Astrocyte adenosine deaminase loss increases motor neuron toxicity in amyotrophic lateral sclerosis. Brain, 142(3), 586-605. View this article in WRRO
- Mutations in the Glycosyltransferase Domain of GLT8D1 Are Associated with Familial Amyotrophic Lateral Sclerosis. Cell Reports, 26(9), 2298-2306.e5. View this article in WRRO
- Stable transgenic C9orf72 zebrafish model key aspects of the ALS/FTD phenotype and reveal novel pathological features. Acta Neuropathologica Communications, 6(1). View this article in WRRO
- Translating SOD1 Gene Silencing toward the Clinic: A Highly Efficacious, Off-Target-free, and Biomarker-Supported Strategy for fALS. Molecular Therapy : Nucleic Acids, 12, 75-88. View this article in WRRO
- TDP-43 induces p53-mediated cell death of cortical progenitors and immature neurons. Scientific Reports, 8(1). View this article in WRRO
- Targeted Genetic Screen in Amyotrophic Lateral Sclerosis Reveals Novel Genetic Variants with Synergistic Effect on Clinical Phenotype. Frontiers in Molecular Neuroscience, 10, 370-370. View this article in WRRO
- C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair. Nature Neuroscience, 20, 1225-1235. View this article in WRRO
- SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits. Nature Communications, 8. View this article in WRRO
- Viral delivery of C9ORF72 hexanucleotide repeat expansions in mice lead to repeat length dependent neuropathology and behavioral deficits.. Disease Models & Mechanisms, 10, 859-868. View this article in WRRO
- C9ORF72 hexanucleotide repeat exerts toxicity in a stable, inducible motor neuronal cell model, which is rescued by partial depletion of Pten. Human Molecular Genetics, 26(6), 1133-1145. View this article in WRRO
- The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy. EMBO Journal, 35(15), 1656-1676. View this article in WRRO
- Oligogenic inheritance of optineurin (OPTN) and C9ORF72 mutations in ALS highlights localisation of OPTN in the TDP‐43‐negative inclusions of C9ORF72‐ALS. Neuropathology, 36(2), 125-134. View this article in WRRO
- Antisense RNA foci in the motor neurons of C9ORF72-ALS patients are associated with TDP-43 proteinopathy. Acta Neuropathologica, 130(1), 63-75. View this article in WRRO
- A neuronal DNA damage response is detected at the earliest stages of Alzheimer's neuropathology and correlates with cognitive impairment in the Medical Research Council's Cognitive Function and Ageing Study ageing brain cohort. Neuropathology and Applied Neurobiology, 41(4), 483-496. View this article in WRRO
- C9ORF72 GGGGCC Expanded Repeats Produce Splicing Dysregulation which Correlates with Disease Severity in Amyotrophic Lateral Sclerosis. PLOS ONE, 10(5), e0127376-e0127376. View this article in WRRO
- Intermediate length C9orf72 expansion in an ALS patient without classical C9orf72 neuropathology. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 16(3-4), 249-251. View this article in WRRO
- Distinct Regions of the Large Extracellular Domain of Tetraspanin CD9 Are Involved in the Control of Human Multinucleated Giant Cell Formation. PLoS ONE, 9(12). View this article in WRRO
- Loss of nuclear TDP-43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones. Neuropathology and Applied Neurobiology, 40(6), 670-685.
- Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions.. Brain, 137(7), 2040-2051. View this article in WRRO
- PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor neurons. Cell Death and Disease, 5(2). View this article in WRRO
- Superoxide dismutase 1 mutation in a cellular model of amyotrophic lateral sclerosis shifts energy generation from oxidative phosphorylation to glycolysis. Neurobiology of Aging, 35(6), 1499-1509.
- A new zebrafish model produced by TILLING of SOD1-related amyotrophic lateral sclerosis replicates key features of the disease and represents a tool for in vivo therapeutic screening. Disease Models & Mechanisms, 7(1), 73-81.
- C9ORF72 transcription in a frontotemporal dementia case with two expanded alleles. Neurology, 81(19), 1719-1721.
- Viral Delivery of Antioxidant Genes as a Therapeutic Strategy in Experimental Models of Amyotrophic Lateral Sclerosis. Molecular Therapy, 21(8), 1486-1496. View this article in WRRO
- S[+] Apomorphine is a CNS penetrating activator of the Nrf2-ARE pathway with activity in mouse and patient fibroblast models of amyotrophic lateral sclerosis. Free Radical Biology and Medicine, 61, 438-452.
- Simultaneous and independent detection of C9ORF72 alleles with low and high number of GGGGCC repeats using an optimised protocol of Southern blot hybridisation. Molecular Neurodegeneration, 8(1), 12-12. View this article in WRRO
- PTEN signalling in motor neuron disease (ALS & SMA). HUMAN GENE THERAPY, 22(10), A64-A64.
- Gene therapy approaches to evaluate neuroprotection in experimental models of Amyotrophic Lateral Sclerosis. HUMAN GENE THERAPY, 22(10), A64-A64.
- Dysregulation of astrocyte–motoneuron cross-talk in mutant superoxide dismutase 1-related amyotrophic lateral sclerosis. Brain, 134(9), 2627-2641.
- PTEN depletion rescues axonal growth defect and improves survival in SMN-deficient motor neurons. Human Molecular Genetics, 19(16), 3159-3168.
- Distinct roles for tetraspanins CD9, CD63 and CD81 in the formation of multinucleated giant cells. Immunology, 127(2), 237-248.
- An in vitro screening cascade to identify neuroprotective antioxidants in ALS. Free Radical Biology and Medicine, 46(8), 1127-1138.
- Characterisation of receptor binding by the chemotaxis inhibitory protein of Staphylococcus aureus and the effects of the host immune response. Molecular Immunology, 44(10), 2507-2517.
- Recombinant Extracellular Domains of Tetraspanin Proteins Are Potent Inhibitors of the Infection of Macrophages by Human Immunodeficiency Virus Type 1. Journal of Virology, 80(13), 6487-6496.
- Impairment of mitochondrial anti-oxidant defence in SOD1-related motor neuron injury and amelioration by ebselen. Brain, 129(7), 1693-1709.
- Comparative Agonist/Antagonist Responses in Mutant Human C5a Receptors Define the Ligand Binding Site. Journal of Biological Chemistry, 280(18), 17831-17840.
- Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation. Blood, 105(7), 2852-2861.
- S19 ribosomal protein dimer augments metal-induced apoptosis in a mouse fibroblastic cell line by ligation of the C5a receptor. Journal of Cellular Biochemistry, 94(3), 540-553.
- TETRASPANIN MICRODOMAINS MEDIATE EFFICIENT PRESENTATION AND FUNCTION OF ENDOTHELIAL ADHESION RECEPTORS DURING LEUKOCYTE EXTRAVASATION. Cardiovascular Pathology, 13(3), 108-108.
- CD81 Is Required for Hepatitis C Virus Glycoprotein-Mediated Viral Infection. Journal of Virology, 78(3), 1448-1455.
- Crystallization of a carbamatase catalytic antibody Fab fragment and its complex with a transition-state analogue. Acta Crystallographica Section D Biological Crystallography, 60(1), 172-174.
- Structural requirements for the inhibitory action of the CD9 large extracellular domain in sperm/oocyte binding and fusion. Biochemical and Biophysical Research Communications, 311(1), 208-214.
- Characterisation of C5a receptor agonists from phage display libraries. Biochemical Pharmacology, 66(9), 1833-1840.
- Antibody cross-linking of human CD9 and the high-affinity immunoglobulin E receptor stimulates secretion from transfected rat basophilic leukaemia cells. Immunology, 99(4), 546-552.
- Identification of Amino Acid Residues in CD81 Critical for Interaction with Hepatitis C Virus Envelope Glycoprotein E2. Journal of Virology, 74(8), 3642-3649.
- Characterization of Hepatitis C Virus E2 Glycoprotein Interaction with a Putative Cellular Receptor, CD81. Journal of Virology, 73(8), 6235-6244.
- Identification of the High Affinity Receptor Binding Region in Human Immunoglobulin E. Journal of Biological Chemistry, 271(13), 7494-7500.
- Mutations in CHMP2B in Lower Motor Neuron Predominant Amyotrophic Lateral Sclerosis (ALS). PLoS ONE, 5(3), e9872-e9872. View this article in WRRO
- The Role of the N-terminal Domain of the Complement Fragment Receptor C5L2 in Ligand Binding. Journal of Biological Chemistry, 282(6), 3664-3671.
Conference proceedings papers
- Gene editing as a potential therapeutic approach for ALS/FTD-associated with expanded C9ORF72. HUMAN GENE THERAPY, Vol. 30(8) (pp A22-A22)
- Inosine reverses motor neuron toxicity observed in amyotrophic lateral sclerosis patient astrocytes with an adenosine deaminase deficiency. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1859 (pp e23-e23)
- Fibroblasts from patients with amyotrophic lateral sclerosis (ALS) associated with mutations in tardbp gene as model of TDP-43 proteinopathy. Journal of the Neurological Sciences, Vol. 357 (pp e49-e49)
- AMYOTROPHIC LATERAL SCLEROSIS ASSOCIATED WITH AN INTERMEDIATE LENGTH GGGGCC REPEAT EXPANSION HAS DISTINCT NEUROPATHOLOGY COMPARED TO PATIENTS WITH LARGER EXPANSIONS. Journal of Neurology, Neurosurgery & Psychiatry, Vol. 85(10) (pp e4.130-e4)
- A neuronal DNA damage response is detected at low Braak stages and correlates with cognitive impairment in the ageing brain. NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, Vol. 40 (pp 31-32)
- 159 Dysregulation of the cross-talk with astrocytes as a contributory factor to motor neuron injury in motor neuron disease. Journal of Neurology, Neurosurgery & Psychiatry, Vol. 83(3) (pp e1.115-e1)
- PTEN Depletion Rescues the beta-Actin Deficit in Axonal Growth Cones in Motoneurons from a Mouse Model of Spinal Muscular Atrophy. NEUROLOGY, Vol. 74(9) (pp A489-A489)
- Oxidative Stress as Target for Neuroprotection in Experimental Models of Amyotrophic Lateral Sclerosis (ALS). NEUROLOGY, Vol. 74(9) (pp A436-A436)
- COMP 264-Unraveling the mechanism of antagonism for human C5a receptor: Comparison of three structurally different antagonists. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 236
- Different ligand-binding mechanisms used by the two C5a receptors, C5L2 and C5aR. Molecular Immunology, Vol. 44(1-3) (pp 237-237)
- Defining the ligand binding site on the human C5a receptor. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, Vol. 231
- Inhibition of sperm-oolemma interactions by the extracellular domains of CD9 and CD81. ANDROLOGY IN THE 21ST CENTURY, SHORT COMMUNICATIONS (pp 565-572)
- Identification of potential ligands for CD63 from random peptide libraries. IMMUNOLOGY, Vol. 89 (pp OM117-OM117)
Preprints
- Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer's disease, Research Square Platform LLC.
- GLT8D1 mutations cause amyotrophic lateral sclerosis via disruption of neurotrophin signalling within membrane lipid rafts, Cold Spring Harbor Laboratory.
- Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer’s disease, Cold Spring Harbor Laboratory.
- A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export suppresses neurodegeneration, Cold Spring Harbor Laboratory.
- Spatio-temporal Proteomic Analysis of Stress Granule disassembly using APEX Reveals Regulation by SUMOylation and links to ALS pathogenesis, Cold Spring Harbor Laboratory.
- Spatio-Temporal Proteomic Analysis of Stress Granule Disassembly Using APEX Reveals Regulation by SUMOylation and Links to ALS Pathogenesis.
- Mutations in the Glycosyltransferase Domain of GLT8D1 Cause Amyotrophic Lateral Sclerosis.
- A cell-penetrant peptide blocking C9ORF72-repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins. Science Translational Medicine, 15(685).