Sheffield Institute for
Translational Neuroscience

Dr Ke Ning MD PhD

Non-clinical Senior Lecturer in Translational Neuroscience


Research Interests

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. 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-mediated gene therapy approaches in ALS, SMA and other degenerative disorders. These studies provide great optimism for the future utility of lentiviral gene delivery as a therapeutic strategy for neurodegenerative diseases.

One of my interests is focussing on PTEN/PI3 Kinase pathway and neuronal survival in vitro and in vivo. My research discoveries have included evidence that depression of PTEN increases neuronal survival (J. Neurosci. 2004;Hum Mol Genet 2010 and Brain 2011) and that a novel leptin signalling pathway is activated by PTEN inhibition (EMBO J 2006 and J. Biol. Chem. 2009); proof-of-concept of regulation of huntingtin aggregation by Arfaptin 2 (Nature Cell Biol. 2002 and PNAS 2002) and evidence for circadian regulation of GABAA by CKI in the rat suprachiasmatic nuclei (Nature Neurosci. 2004).

Current Projects

  1. Characterisation of the motor neurons obtained from induced pluripotent stem cells (iPS) in Amyotrophic lateral sclerosis (ALS)
  2. SMN Replacement Therapy for Spinal Muscular Atrophy: Clinical Development
  3. Arfapin 2 regulates protein aggregation and survival in ALS
  4. Characterisation of electrophysiology in motor neuron disease
  5. PTEN signalling in motor neuron survival

Research Team

Dr Ke Ning and research team

PhD Students

  • Aida Mohammedeid
  • Aziza R Alrafiah
  • Dr Azza Ismail
  • Cassy Ashman

Publications

Key Publications:

Ciervo Y, Ning K, Xu J, Shaw PJ, Mead RJ. (2017) Advances, challenges and future directions for stem cell therapy in amyotrophic lateral sclerosis. Mol Neurodegener(In press)

Godena VK, Ning K. (2017) Phosphatase and Tensin homologue (PTEN): A Therapeutic Target for SMA.  Signal Transduct Target Ther(In press) 

Dong CMWang XLWang GMZhang WJZhu LGao SYang DJQin YLiang QJChen YLDeng HTNing KLiang ABGao ZLXu J. (2017) A stress-induced cellular aging model with postnatal neural stem cells. Cell Death Dis. 8(9):e3041.

Hautbergue G, Castelli L, Ferraiuolo L, Sanchez-Martinez A , Cooper-Knock J, Dodd J, Higginbottom A, Garneret P, Stopford M, Karyka E, Meyer K, Kirby J, Kaspar B, De Vos K, Ning K, Azzouz M, Whitworth A, Shaw JS. (2017) SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits. Nat Commun. 8:16063

Wang X, Dong C, Sun L, Zhu L, Sun C, Ma R, Ning K, Lu B, Zhang J, Xu J. (2016)

Quantitative proteomic analysis of age-related subventricular zone proteins associated with neurodegenerative disease. Sci Rep. 6:37443.

Seytanoglu A, Alsomali NI, Valori CF, McGown A, Kim HR, Ning K, Ramesh T, Sharrack B, Wood JD, Azzouz M.(2016) Deficiency in the mRNA export mediator Gle1 impairs Schwann cell development in the zebrafish embryo. Neuroscience, 322:287-297.

LittleD, ValoriCF, MutsaersCA, BennettEJ, WylesM, SharrackB, ShawPJ, GillingwaterTH, Mimoun AzzouzM, Ning K. (2015) PTEN Depletion Decreases Disease Severity and Modestly Prolongs Survival in a Mouse Model of Spinal Muscular Atrophy. Molecular Therapy 

Mohammedeid AM, Lukashchuk V, Ning K. (2014) Protein aggregation and Arfaptin2: A novel therapeutic target against neurodegenerative diseases. New Horizons in Translational Medicine, 2: 12–15. (Review)

Dong C, Wang X, Wang G, Zhang W, Zhu L, Gao S, Yang D, Qing Y, Cheng Y, Deng H, Ning K, Liang A, Gao Z, Liang Q, Xu J.(2014) A stress-induced cellular aging model with postnatal neural stem cells. Cell Death and Disease 2014 Mar 13; 5: e1116.

Yang D, Wang XL, Ismail A, Ashman CJ, Valori CF, Wang G, Gao S, Higginbottom A, Ince PG, Azzouz M, Xu J, Shaw PJ, Ning K (2014). PTEN regulates AMPA receptor-mediated cell viability in iPS-derived motor neurons. Cell Death and Disease; 2014 Feb 27; 5: e1096.

Gao S, Zhao P, Lin C, Sun Y, Wang Y, Zhou Z, Yang D, Wang X, Xu H, Zhou F, Cao L, Zhou W, Ning K, Chen X, Xu J (2013). Differentiation of Human-Adipose Derived Stem Cells into neuron-like cells which are compatible with photocurable three-dimensional scaffolds.
Tissue Eng Part A. 2013 Nov 19. [Epub ahead of print]

Nanou A, Higginbottom A, Valori CF, Wyles M, Ning K, Shaw P, Azzouz M( 2013). Viral Delivery of Antioxidant Genes as a Therapeutic Strategy in Experimental Models of Amyotrophic Lateral Sclerosis. Molecular Therapy, 21(8):1486-96.

Brockington A, Ning K, Heath RH, Wood E, Fusi N, Lawrence N, Wharton NB, Ince PG, Shaw PJ. (2013). 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 Neuropathologica, 125(1):95-109.

Ismail A, Ning K, Al-Hayani A, Sharrack B, Azzouz M (2012). PTEN: A molecular target for neurodegenerative disorders. Translational Neuroscience, 3(2). DOI:10.2478/s13380-012-0018-9.

Kirby J*, Ning K*, Ferraiuolo L, Heath PR, Ismail A, Kuo SW, Valori CF, Cox L,Sharrack B, Wharton SB, Ince PG, Shaw P & Azzouz M. (2011) PTEN/AKT pathway linked to motor neuron survival in human SOD1-related amyotrophyic lateral sclerosis. Brain, 134(Pt 2):506-17. (*Joint first and corresponding authors)

Valori CF*, Ning K*, Wyles M, Mead R., Grierson A., Shaw P., Azzouz M. (2010). Systemic Delivery of scAAV9 expressing SMN Prolongs Survival in a Model of Spinal Muscular Atrophy. Science Translational Medicine, 2 (35):35ra42 *Contributed equally to this work)

Ning K, Drepper C, Valori C, Wyles M, Higginbottom A, Shaw P, Azzouz M, Sendtner M (2010). PTEN depletion rescues axonal growth defect and improve survival in SMN-deficient motor neurons. Human Molecular Genetics, 19 (16):3159-68

Ning K., Miller L.C., Laidlaw H. A., Watterson K.R., Gallagher J., Sutherland C. and Ashford M.L.J. (2009) Leptin dependent phosphorylation of PTEN mediates actin restructing and actvation of ATP-sensitive K+ channels. The Journal of Biological Chemistry 284(14):9331-40

Valori CF, Ning K., Wyles M. and Azzouz M. (2008) Applications of Lentiviral Vectors for biology and gene therapy of neurological disorders. Current Gene Therapy Dec;8(6):406-18

Li L, El-Hayek YH, Liu B, Chen Y, Gomez E, Wu X, Ning K, Li L, Chang N, Zhang L, Zhengguo W, Hu X, Wan Q. (2008) Direct-current Electrical Field Guides Neuronal Stem/progenitor Cell Migration. Stem Cells. 26(8):2193-200

Ning, K., Miller, L., Burgess, L.A., Laidlaw HA, Perera, N., Downes, C.P., Leslie, N.R.,& Ashford, M.L.J. (2006) A novel leptin signaling pathway via PTEN inhibition in hypothalamic cell lines and pancreatic ß-cells. The EMBO Journal 25(11):2377-2387

Liu, B., Liao, M., Mielke, J.G., Ning, K., Chen, Y., Li, L., EI-Hayek, Y.H., Gomez, E., Zukin, R.S., Fehlings, M.G., Wan, W. (2006) Ischemic insults direct glutamate receptor subunit 2-lacking AMPA receptors to synaptic sites. The Journal of Neuroscience 26(20):5309-5319

Mirshamsi S., Laidlaw H.A., Ning, K., Anderson E., Burgess L.A., Gray A., Sutherland C., Ashford M.L.J. (2004) Stimulation of PI3K by leptin and insulin leads to actin reognization and KATP activation in arcuate nucleus neurons. BMC Neuroscience 5, 54

Ning, K., Li, L., Liao, M., Liu, B., Mielke, J.G., Chen, Y., Duan, Y., Hayek, Y.H., Wan, Q. (2004) Circadian regulation of GABA-A receptor function by CKI in the rat suprachiasmatic nuclei. Nature Neuroscience 7(5): 489-490.

Ning K., Pei, P., Liao, M., Liu, B., Zhang, Y., Jiang, W., Mielke, J.G., Li, L., Chen, Y., Hayek, Y.H., Fehlings, M.G., Zhang, X., Liu, F., Eubanks, J., and Wan, Q. (2004) Dual neuroprotective signaling mediated by two distinct phosphatase activities of PTEN. The Journal of Neuroscience 24(16): 4052-4060

Peters, P.J.*, Ning, K.*, Palacios, F., Kazantsev, A., and Crislyn D'Souza-Schorey (2002) Arfaptin 2 regulates aggregation of mutant huntingtin protein. Nature Cell Biology 4(3):240-245 (*Peters and *Ning Contributed equally)

Muchowski, P.J., Ning, K., D'Souza-Schorey, C., and Fields, S. (2002) Requirement of an intact microtubule cytoskeleton for aggregation and inclusion body formation by a mutant huntingtin fragment. Proc. Natl. Acad. Sci. USA 99(2): 727-732

Professional Activities

I am a regular manuscript or grant reviewer for journals or funders in China, UK and Europe. I am an executive Committee Member of Chinese Life Scientists Society in the UK. I am a SOP representative and reviewer for TREAT-NMD (An European Network of Excellence addressing the fragmentation currently hindering translational research for cutting edge therapies in rare neuromuscular diseases). I am a member of the Society for Neurosciences, a member of the American Society of Gene Therapy, a member of the British Society of Gene Therapy and a European Society for Translational Medicine (EUSTM) Expert Panel Member.

Biography

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.

Teaching Interests

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 Department of Neuroscience for postdoctoral training at the University of Sheffield. I am a primary supervisor for MSc and Ph.D students and a mentor for Medical students.

Contact Details

Academic Neurology Unit
Department of Neuroscience
Sheffield Institute for Translational Neuroscience
University of Sheffield
Room B46
385a Glossop Road
Sheffield
S10 2HQ

T: +44 (0) 114 2222245
F: +44 (0) 114 2222290
E: k.ning@sheffield.ac.uk

Secretary: 
Bev Carter
T: +44 (0)114 2222295
E: bev.carter@sheffield.ac.uk