Neurological

Neurons derived from patient specific iPS cells demonstrating  co-expression of vGLut1 (green) and Beta-III-Tubulin (red). Image courtesy of Lisa Mohamet.

Neurological

Our research comprises stem cell and gene therapies to treat neurological genetic diseases, as well as methods to improve nerve regeneration.  This includes the use of iPS cells to help elucidate the molecular aetiology of Alzheimer’s disease and utilising novel polymer nerve conduits to enhance peripheral nerve regeneration.

Academic

Professor Nigel Hooper

Professor of Cell Biology
Faculty of Biology, Medicine and Health
nigel.hooper@manchester.ac.uk
Professor Hooper’s University Profile

Cell Biology of Alzheimer’s Disease

Alzheimer’s disease is characterised by the accumulation in the brain of the amyloid-β (Aβ) peptide, which is derived from the larger transmembrane amyloid precursor protein (APP) through the sequential proteolytic action of the β- and γ-secretases. Understanding the molecular and cellular mechanisms that regulate APP processing and Aβ production, including the impact of proteins identified from genetic screens, and the role of alternative processing pathways, is critical to our understanding of the disease. Work in his group includes developing stem cell models of Alzheimer’s disease, investigation into neuronal zinc metabolism, and the post-translational processing of the low density lipoprotein receptor. Additionally, they are developing a three-dimensional model for neural stem cell differentiation and its application to Alzheimer’s disease (funded by MRC).

Professor Stuart Allan

Professor of Neuroscience
Faculty of Biology, Medicine and Health
stuart.allan@manchester.ac.uk
Professor Allan’s University Profile

Neuro-degeneration and Regeneration

Professor Allan’s research focuses on the molecular mechanisms mediating neuro-degeneration and the use of this knowledge to design regenerative therapies.  His group have focused on role of the pro-inflammatory cytokine interleukin-1 (IL-1) in post-stroke neuroinflammation, showing that inhibition of IL-1 activity, through treatment with IL-1 receptor antagonist (IL-1Ra), not only increases stem cell proliferation, but also significantly enhances neuroblast migration and the number of newly born neurons after cerebral ischemia, as well as reducing the initial injury. His group’s data demonstrate that systemic administration of IL-1Ra improves outcome and promotes neurogenesis after experimental stroke, highlighting the therapeutic potential of this clinically approved drug.Professor Allan’s regenerative research also extends to the use of mesenchymal stem cells, alone and in conjunction with novel-hydrogels, as a potential treatment for neuroinflammation post-stroke.

Dr Emmanuel Pinteaux

Senior Lecturer
Faculty of Biology, Medicine and Health
emmanuel.pinteaux@manchester.ac.uk
Dr Pinteaux’s University Profile

Role of Inflammation in Brain Tissue Repair After Stroke

Dr. Pinteaux’s research programme focuses on the regenerative potential of brain tissue after acute injury, such as stroke. His group focus on three major themes:

  1. The use of stem cells and nanotechnologies to promote brain tissue repair
  2. Use of IL1α to promote angiogenesis post stroke.
  3. Understand the role of the acute phase protein pentraxin-3 as a regulator of brain tissue repair after stroke.

Dr. Pinteaux’s research ranges from basic to the preclinical stages of translation.

Dr Brian Bigger

Reader
Faculty of Biology, Medicine and Health
brian.bigger@manchester.ac.uk
Dr Bigger’s University Profile

Gene Therapy for Neurological Diseases

Neurodegenerative metabolic diseases mainly affect children and often lack effective treatments. Dr Bigger’s Stem Cell & Neurotherapies laboratory works on understanding the pathology and delivering stem cell and gene therapy treatments for both mucopolysaccharide diseases (a type of lysosomal storage disorder affecting the brain) and gliomas (brain tumours). The lab uses a multidisciplinary approach including development of a novel substrate reduction drug for Sanfilippo disease, currently in phase III trial, haematopoietic stem cell gene therapy for Sanfilippo disease A and B, as well as Hunter disease, and a gene therapy approach for MPSIIIC. In order to develop effective treatments, a complete understanding of the underlying pathology in mouse models and their comparison to patients is critical, and assists with the development of suitable biomarkers and clinical outcome measures for subsequent trials. This approach is also being used to develop novel immunotherapies and to repurpose existing drugs for treatment of gliomas.

Dr Natalie Gardiner

Lecturer
Faculty of Biology, Medicine and Health
natalie.gardiner@manchester.ac.uk
Dr Gardiner’s University Profile

Diabetic Neuropathy: Changes in Sensory Neuronal Phenotype

The incidence and severity of neuropathy in patients with diabetes is worsened by poor hyperglycaemic control, indicating high glucose levels to be a primary causative factor. Distal sensory polyneuropathy (DPN) is the most common of the peripheral nerve disorders associated with diabetes (~54% of type 1 diabetic patients develop DPN). DPN can be accompanied by: pain, tingling and burning sensations; heightened sensitivity; numbness; and ultimately loss of sensation, which may lead to tissue damage. It is a debilitating condition, with no effective treatment.The degeneration of sensory nerve terminals in the skin, and subsequent failure of reinnervation is a key pathological feature of DPN. The cause of this regenerative deficit is complex – a combination of phenotypic change, oxidative stress, reduced growth factors, impaired synthesis and axonal transport of cytoskeletal components, and associated biochemical changes including formation of advanced glycation endproducts (AGEs.

The success of sensory nerve regeneration depends largely on two factors: the presence of a permissive growth environment and the intrinsic growth capacity of the neuron. The extracellular matrix (ECM) not only provides important physical structure and support for cells and tissue, but also has a crucial role in regulating cell behaviour, mediating survival, proliferation, differentiation and migration via interaction with specific cell adhesion receptors such as the integrins. Therefore, modification ECM proteins in disease, such as by glycation in diabetes, can severely impact on cell function.

Dr Gardiner’s group have recently shown that AGEs accumulate in ECM proteins of peripheral nerve in experimental diabetes, and that glycation of the ECM proteins laminin and fibronectin, with either glucose or methylglyoxal, increases AGE residue content of these proteins and dramatically impairs regeneration of sensory neurons in vitro. They hope to elucidate the changes in the sensory nervous system in diabetes, to develop effective therapeutic strategies for treating diabetic neuropathy.

Dr Lisa Mohamet

Research Fellow
Faculty of Biology, Medicine and Health
lisa.mohamet@manchester.ac.uk
Dr Mohamet’s University Profile

Differentiation of Neural Progenitor Cells from ES and iPS Cells

Dr Mohamet collaborates with Dr Ward’s group; their regenerative research focuses on the generation of neural precursor cells from both ES and iPS cells.  They also specialise in the isolation of iPS cells from Alzheimer’s disease patients to model tau aggregation. Current projects also aim to exploit their science for commercial applications, including ES cell bioreactor culture and novel cadherin interacting peptides.

Professor Rob Lucas

Professor of Neurobiology
Faculty of Biology, Medicine and Health
robert.lucas@manchester.ac.uk
Professor Lucas’s University Profile
Lucas Group Website

Biology of Light Perception

Professor Lucas is interested in how mammals measure illumination and how we use this information to regulate aspects of our behaviour and physiology. His past work has contributed to the discovery that measuring ambient light relies, in part, on a new type of photoreceptor cell, which is distinct from the well-known rods and cones. This new photoreceptor is found among the retinal ganglion cells that form the origin of the optic nerve and relies upon a new photopigment called melanopsin, for its photosensitivity. Melanopsin photoreceptors act in concert with rods and cones, and one aspect of his ongoing work concerns how the sensory capacities of these three systems complement one another. Another strand of his research concerns the physiological systems downstream of melanopsin photoreceptors.   His group have identified a role for these photoreceptors in adjusting circadian clocks in the brain and retina, also in driving pupillomotor movements.  They are interested in understanding more about the quality of light information reaching these systems, as well as identifying melanopsin contributions to other aspects of our sensory biology. One of Professor Lucas’s particular interest is the degree to which information about ambient illuminance impinges upon conventional visual pathways.

The practical application of Professor Lucas’s work are expressed in the use of non-visual photopigments to generate optogenetic tools targeting G-protein coupled receptors and the use of iPS cell technology to generate experimental models for understanding photoreception.  Recently, Prof. Lucas’s group has demonstrated that virally mediated ectopic expression of human rod opsin can restore vision under natural viewing conditions and at moderate light intensities; this suggests that rod opsin merits consideration as an gene therapy in humans.

Academic-Clinical

Dr Adam Reid

Senior Clinical Lecturer Honorary Consultant in Plastic Reconstructive Surgery
Faculty of Biology, Medicine and Health
University Hospital of Southern Manchester
adam.reid@manchester.ac.uk
Dr Reid’s University Profile

Peripheral Nerve Regeneration

Adam Reid is a Senior Clinical Lecturer in Plastic & Re-constructive Surgery with academic and clinical interests in trauma, nerve injury and complex limb reconstruction. Dr Reid leads a research team in the Blond McIndoe Laboratories at the University of Manchester and works clinically at the University Hospital of South Manchester. In collaboration with Professor Julie Gough he is poised to conduct a NIHR supported, first in man study, on a novel polymer nerve conduit, for peripheral nerve regeneration at the University Hospital of South Manchester. Additionally,  he is developing novel applications for adipose-derived stem cells, in peripheral nerve regeneration. This work is supported by funding from the National Institute for Health Research, the Healing Foundation and the Academy of Medical Sciences.

Clinical

Dr Monty Silverdale

Consultant Neurologist
Greater Manchester Neuroscience Centre,
Salford Royal NHS Foundation Trust

Honorary Lecturer
University of Manchester
Division of Neuroscience & Experimental Psychology

Monty.Silverdale@manchester.ac.uk
Dr Silverdale’s University Profile

Biomarker Discovery for Parkinson’s Disease

Dr. Silverdale is a consultant neurologist specializing in Parkinson’s disease (PD) and movement disorders. His clinical duties include  a central role in leading the complex PD and movement disorder service at the Greater Manchester Neuroscience. Dr Silverdale’s regenerative medicine research focuses on the discovery and use of novel biomarkers to allow the early diagnosis and tracking of disease progression for Parkinson ’s Disease. He is the lead clinical researcher in a Parkinson’s UK funded trial investigating the potential of metabolic changes in skin sebum, which may lead to changes in skin odour, as pre-symptomatic biomarkers of PD. His is also leading a Michael J Fox foundation funded trial investigating the use of corneal confocal microscopy to provide a rapid non-invasive detection system for small fibre neuropathy, as an objective indicator of disease progression. Dr Silverdale’s research will underpin the ability to both develop new therapies for PD and improve their efficacy; the use of corneal confocal microscopy has the potential to provide an objective measure of disease progression, which will dramatically accelerate the development of novel neuroportecive and neuroregenerative treatments, whilst the ability to diagnose sub-clinical disease, via novel biomarkers, offers the possibility to greatly improve the efficacy of regenerative therapies, for 60% of neurodegeneration occurs prior to diagnosis of PD.