Dr Ke Ning
MD, PhD
School of Medicine and Population Health
Non-clinical Senior Lecturer in Translational Neuroscience
k.ning@sheffield.ac.uk
+44 114 222 2245
+44 114 222 2245
+44 114 222 2278
(Administrator: Heather Cartledge)
Room B46, Sheffield Institute for Translational Neuroscience (SITraN)
Full contact details
Dr Ke Ning
School of Medicine and Population Health
Room B46
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
School of Medicine and Population Health
Room B46
Sheffield Institute for Translational Neuroscience (SITraN)
385a Glossop Road
Sheffield
S10 2HQ
- Profile
-
I graduated in Medicine from First Military Medical University (Southern Medical University) in China in 1985. I undertook my Specialist Training in Neurosurgery at Sun Yatsen University of Medical Science in China and got a M.Sc in Neurosurgery in 1991.
I obtained my PhD in neuroscience at the Third Military Medical University in China In 1996 and was promoted to an associate professor in neurosurgery at Southern Medical University in China in 1997.
Since 1999, I have undertaken full time research in neuroscience in the USA, Canada and the UK. I joined the University of Sheffield as a Lecturer in Translational neuroscience in 2006 and was promoted to a Senior Lecturer in Translational Neuroscience in 2011.
I have been closely involved in translational neuroscience research and teaching in motor neuron diseases.
- Research interests
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The focus of my research is the use of viral vector-mediated gene therapy and stem cell strategies to treat neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). ALS/MND is a common adult onset neurodegenerative disease characterised by progressive degeneration of motor neurones in the brainstem and spinal cord.
There is no effective treatment or cure for MND/ALS and other neurodegenerative disorders. Gene therapy approaches offer a promising strategy for delivery of genes to enhance motor neuron survival. New approaches for the treatment of neurological disorders have been developed by using lentiviruses and other viruses (Adeno-associate virus AAV6, AAV9 and so on).
These vectors have been refined to a very high safety and efficiency levels. Lentiviruses are particularly advantageous for use in gene transfer to the nervous system. Numerous animal studies have now been undertaken with these vectors and correction of disease models has been obtained.
Recent studies have demonstrated very good efficacy of Lentiviral- or AAV9-mediated gene therapy approaches in ALS, SMA and other degenerative disorders. These studies provide great optimism for the future utility of lentiviral or AAV gene delivery as a therapeutic strategy for neurodegenerative diseases.
- SMA Trust Project
- MRC Project
- MNDA Project
- Publications
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Journal articles
- Lipid-based nanoparticles for drug delivery in Parkinson’s disease. Translational Neuroscience, 15(1), 20220359.
- Serine and arginine rich splicing factor 1: a potential target for neuroprotection and other diseases. Neural Regeneration Research, 18(7), 1411-1411.
- ADSCs-derived exosomes ameliorate hepatic fibrosis by suppressing stellate cell activation and remodeling hepatocellular glutamine synthetase-mediated glutamine and ammonia homeostasis. Stem Cell Research & Therapy, 13(1).
- An insight into the iPSCs-derived two-dimensional culture and three-dimensional organoid models for neurodegenerative disorders. Interface Focus, 12(5).
- SMN-deficient cells exhibit increased ribosomal DNA damage. Life Science Alliance, 5(8), e202101145-e202101145.
- Rebuilding hippocampus neural circuit with hADSC-derived neuron cells for treating ischemic stroke. Cell & Bioscience, 12(1).
- Sirt1 protects subventricular zone-derived neural stem cells from DNA double-strand breaks and contributes to olfactory function maintenance in aging mice. Stem Cells.
- Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis. Neuron.
- SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export : genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis. Molecular Neurodegeneration, 16(1).
- Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives. Development, 148(6). View this article in WRRO
- Glucosylpolyphenols as inhibitors of Aβ-induced Fyn kinase activation and Tau phosphorylation: synthesis, membrane permeability, and exploratory target assessment within the scope of type 2 diabetes and Alzheimer’s disease. Journal of Medicinal Chemistry.
- Multiple injections of autologous adipose-derived stem cells accelerate the burn wound healing process and promote blood vessel regeneration in a rat model. Stem Cells and Development, 28(21), 1463-1472. View this article in WRRO
- Differentiation of human adipose-derived stem cells into neuron/motoneuron-like cells for cell replacement therapy of spinal cord injury. Cell Death & Disease, 10(8). View this article in WRRO
- Discovery of N-methylpiperazinyl flavones as a novel class of compounds with therapeutic potential against Alzheimer’s disease: synthesis, binding affinity towards amyloid β oligomers (Aβo) and ability to disrupt Aβo-PrPC interactions. Pure and Applied Chemistry, 91(7). View this article in WRRO
- Stress-induced precocious aging in PD-patient iPSC-derived NSCs may underlie the pathophysiology of Parkinson’s disease. Cell Death & Disease, 10(2). View this article in WRRO
- Astrocytic miR-324-5p is essential for synaptic formation by suppressing the secretion of CCL5 from astrocytes. Cell Death & Disease, 10(2). View this article in WRRO
- Plastin 3 promotes motor neuron axonal growth and extends survival in a mouse model of spinal muscular atrophy. Molecular Therapy - Methods and Clinical Development, 9, 81-89. View this article in WRRO
- SRSF1-dependent nuclear export of C9ORF72 repeat transcripts: targeting toxic gain-of-functions induced by protein sequestration as a selective therapeutic strategy for neuroprotection. Therapeutic Targets for Neurological Diseases, 4. View this article in WRRO
- Extracellular Vesicles Secreted by Human Adipose-derived Stem Cells (hASCs) Improve Survival Rate of Rats with Acute Liver Failure by Releasing lncRNA H19. EBioMedicine, 34, 231-242. View this article in WRRO
- Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis. Molecular Neurodegeneration, 12, 85-85. View this article in WRRO
- A stress-induced cellular aging model with postnatal neural stem cells. Cell Death and Disease, 8(9).
- Therapeutic strategies for spinal muscular atrophy: SMN and beyond.. Dis Model Mech, 10(8), 943-954. 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
- Phosphatase and tensin homologue: a therapeutic target for SMA. Signal Transduction and Targeted Therapy, 2(1). View this article in WRRO
- Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease. Scientific Reports, 6. View this article in WRRO
- Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo. Neuroscience, 322, 287-297. View this article in WRRO
- PTEN Depletion Decreases Disease Severity and Modestly Prolongs Survival in a Mouse Model of Spinal Muscular Atrophy. Molecular Therapy, 23(2), 270-277. View this article in WRRO
- A stress-induced cellular aging model with postnatal neural stem cells.. Cell Death Dis, 5, e1116. View this article in WRRO
- PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor neurons.. Cell Death Dis, 5, e1096. View this article in WRRO
- Differentiation of Human-Adipose Derived Stem Cells into neuron-like cells which are compatible with photocurable three-dimensional scaffolds.. Tissue Eng Part A..
- Viral delivery of antioxidant genes as a therapeutic strategy in experimental models of amyotrophic lateral sclerosis.. Mol Ther, 21(8), 1486-1496. View this article in WRRO
- Unravelling the enigma of selective vulnerability in neurodegeneration: motor neurons resistant to degeneration in ALS show distinct gene expression characteristics and decreased susceptibility to excitotoxicity.. Acta Neuropathol, 125(1), 95-109. View this article in WRRO
- PTEN: A molecular target for neurodegenerative disorders. TRANSLATIONAL NEUROSCIENCE, 3(2), 132-142.
- Impact of PTEN modulation on motor neuron survival in experimental models of motor neuron disease. HUMAN GENE THERAPY, 22(10), A62-A62.
- Polymersome mediated gene therapy for spinal muscular atrophy. HUMAN GENE THERAPY, 22(10), A83-A84.
- 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.
- Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis.. Brain, 134(Pt 2), 506-517. View this article in WRRO
- Developing standard procedures for pre-clinical efficacy studies in mouse models of spinal muscular atrophy. Neuromuscular Disorders, 21(1), 74-77.
- Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy.. Sci Transl Med, 2(35), 35ra42.
- Leptin-dependent phosphorylation of PTEN mediates actin restructuring and activation of ATP-sensitive K+ channels.. J Biol Chem, 284(14), 9331-9340.
- Development and applications of non-HIV-based lentiviral vectors in neurological disorders.. Curr Gene Ther, 8(6), 406-418.
- Direct-current electrical field guides neuronal stem/progenitor cell migration.. Stem Cells, 26(8), 2193-2200.
- A novel leptin signalling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic beta-cells.. EMBO J, 25(11), 2377-2387.
- Ischemic insults direct glutamate receptor subunit 2-lacking AMPA receptors to synaptic sites.. J Neurosci, 26(20), 5309-5319.
- Leptin and insulin stimulation of signalling pathways in arcuate nucleus neurones: PI3K dependent actin reorganization and KATP channel activation.. BMC Neurosci, 5, 54. View this article in WRRO
- Circadian regulation of GABAA receptor function by CKI epsilon-CKI delta in the rat suprachiasmatic nuclei.. Nat Neurosci, 7(5), 489-490.
- Dual neuroprotective signaling mediated by downregulating two distinct phosphatase activities of PTEN.. J Neurosci, 24(16), 4052-4060.
- Arfaptin 2 regulates the aggregation of mutant huntingtin protein.. Nat Cell Biol, 4(3), 240-245.
- Requirement of an intact microtubule cytoskeleton for aggregation and inclusion body formation by a mutant huntingtin fragment.. Proc Natl Acad Sci U S A, 99(2), 727-732.
- Effects of excitatory amino acids and nimodipine on calcium currents in cultured rat cortical neurons.. Zhongguo Yao Li Xue Bao, 20(4), 329-332.
- PTEN as a therapeutic target in motor neuron diseases (ALS/SMA). European Journal of Molecular & Clinical Medicine, 2(2), 68-68.
- Amyloid binding and beyond: a new approach for Alzheimer's disease drug discovery targeting Aβo–PrPC binding and downstream pathways. Chemical Science.
Conference proceedings papers
- Identification of Arfaptin-2 as a Potential Therapeutic Target for Amyotrophic Lateral Sclerosis (ALS) Using iPSC-Derived Motor Neurons and Zebrafish as Models of ALS. MOLECULAR THERAPY, Vol. 30(4) (pp 298-299)
- Spinal muscular atrophy: The combined effect of coSMN expression and PTEN depletion in vitro. HUMAN GENE THERAPY, Vol. 30(8) (pp A20-A20)
- PTEN as therapeutic target for spinal muscular atrophy (SMA). HUMAN GENE THERAPY, Vol. 30(8) (pp A26-A26)
- Establishing cerebral organoids as models for amyotrophic lateral sclerosis (ALS). HUMAN GENE THERAPY, Vol. 30(8) (pp A28-A28)
- Arfaptin-2 as a therapeutic target for amyotrophic lateral sclerosis (ALS). HUMAN GENE THERAPY, Vol. 30(8) (pp A19-A20)
- Adipose derived stem cells for cell therapy of motor neuron disease (MND). HUMAN GENE THERAPY, Vol. 30(8) (pp A16-A16)
- A stem cell model of spinal muscular atrophy (SMA): Assessing combinatorial drug therapies. HUMAN GENE THERAPY, Vol. 30(8) (pp A12-A13)
- Deficiency in Gle1, an mRNA export mediator, inhibits Schwann cell development in the zebrafish embryo. FEBS JOURNAL, Vol. 281 (pp 771-771)
- Regulation of protein aggregation by Arfaptin2 in amyotrophic lateral sclerosis. HUMAN GENE THERAPY, Vol. 25(5) (pp A14-A14)
- Systemic delivery of scAAV9 expressing PTEN siRNA prolongs survival in a model of spinal muscular atrophy. HUMAN GENE THERAPY, Vol. 24(5) (pp A27-A27)
- Efficient scAAV9-mediated delivery of SMN to motor neurons in neonatal and juvenile mice. HUMAN GENE THERAPY, Vol. 24(5) (pp A38-A38)
- MOTOR NEURONES SUBTYPES RESISTANT TO DEGENERATION IN AMYOTROPHIC LATERAL SCLEROSIS SHOW DISTINCT SYNAPTIC CHARACTERISTICS ACROSS SPECIES. JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol. 83(3)
- Systemic delivery of scAAV9 expressing SMN prolongs survival in a mouse model of SMA. HUMAN GENE THERAPY, Vol. 21(10) (pp 1424-1425)
- Current Advances in Gene Therapy for Spinal Muscular Atrophy. HUMAN GENE THERAPY, Vol. 21(10) (pp 1388-1389)
- Complete Rescue of SMA Mouse Model by Systemic Delivery of scAAV9 Mediating SMN Replacement. NEUROLOGY, Vol. 74(9) (pp A287-A287)
- Oxidative Stress as Target for Neuroprotection in Experimental Models of Amyotrophic Lateral Sclerosis (ALS). NEUROLOGY, Vol. 74(9) (pp A436-A436)
- 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)
- Optimizing EIAV vectors and delivery routes for ALS gene therapy. HUMAN GENE THERAPY, Vol. 19(4) (pp 405-405)
- Regulation of NMDA receptors by the phosphatase PTEN. JOURNAL OF NEUROCHEMISTRY, Vol. 102 (pp 147-147)
- Regulation of neuronal migration by direct-current electrical fields in the developing brain. INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, Vol. 24(8) (pp 590-591)
- Dual neuroprotective signaling mediated by downregulating two distinct phosphatase activities of PTEN. JOURNAL OF NEUROCHEMISTRY, Vol. 90 (pp 146-146)
Preprints
- Rebuilding Hippocampus Neural Circuit with hADSC-derived Neuron Cells for Treating Ischemic Stroke, Research Square Platform LLC.
- Safety and efficacy of C9ORF72-repeat RNA nuclear export inhibition in amyotrophic lateral sclerosis, Cold Spring Harbor Laboratory.
- Defining the signalling determinants of a posterior ventral spinal cord identity in human neuromesodermal progenitor derivatives.
- Lipid-based nanoparticles for drug delivery in Parkinson’s disease. Translational Neuroscience, 15(1), 20220359.
- Research group
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- Dr Ana Maria Sandoval (Postdoctoral Research Associate)
- Jie Ren (PhD student)
- Anushka Bhargava (PhD student)
- Teaching interests
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The focus of my teaching is the use of inquiry-based learning (IBL) methods to teach (MSc lectures) or supervise undergraduate projects (SSC) and graduate (MSc and PhD) students.
I am the representative ECG (The Early Career Group) committee member for the Division of Neuroscience for postdoctoral training at the University of Sheffield. I am a primary supervisor for MSc and PhD students and a mentor for Medical students.
- Current Projects
- Characterisation of the motor neurons obtained from induced pluripotent stem cells (iPS) in Amyotrophic lateral sclerosis (ALS)
- SMN Replacement Therapy for Spinal Muscular Atrophy: Clinical Development
- Arfapin 2 regulates protein aggregation and survival in ALS
- Characterisation of electrophysiology in motor neuron disease
- PTEN signalling in motor neuron survival
- Development and validation of a human brain microphysiological system derived from induced pluripotent stem cells in amyotrophic lateral sclerosis (ALS)