• Professor of Cell And Gene Therapy, University of Manchester
• Head of Business Engagement, School of Biological Sciences
• Chairman, European Study Group on Lysosomal Diseases

Dr Bigger was awarded a Bachelors degree from the University of Bath in Applied Biology. His PhD was conducted in the Gene Therapy Research Group, Imperial College, London, where he worked with Professor Charles Coutelle on developing a gene delivery vehicle for mitochondrial gene therapy. On completion of his PhD in 2000, Dr Bigger joined Dr Mike Themis, Imperial College, London to work on a Wellcome Trust collaborative project with Cancer Research UK, investigating gene delivery to stem cells for liver diseases. In 2004 he joined Dr Suzanne Watt’s group in Oxford University and the National Blood Service as a Senior Research Scientist to work on mechanisms of stem cell homing. In 2006 Dr Bigger set up the Stem Cell & Neurotherapies laboratory at the University of Manchester and the Royal Manchester Children's hospital.

Neurodegenerative metabolic diseases mainly affect children and often lack effective treatments.  Some, such as the lysosomal storage disease, Mucopolysaccharidosis (MPS) I, can already be partly treated by allogeneic transplantation of bone marrow or cord blood derived stem cells from a healthy donor, but there is often a high associated risk of morbidity and mortality when using mismatched transplants.

Dr Bigger’s Stem Cell & Neurotherapies laboratory uses a multidisciplinary approach to investigate stem cell and gene therapies for neurological diseases. It consists of two programmes

MPS lysosomal disease group

1. Comparative neuropathology and mechanisms of neurodegeneration in models of MPS disease
2. Clinical development of novel stem cell and gene therapies in neurodegenerative lysosomal diseases
3. Biomarker development
4. The therapeutic use of haematopoietic stem cell transplantation in neurodegenerative disease
5. The use of substrate reducing agents to ameliorate mucopolysaccharide diseases.

The Brain Tumour group

1. Brain tumour stem cell biology and their interaction with Microglia in vivo
2. Novel therapies for brain tumours using high throughput drug screening in cancer stem cell lines derived from primary gliomas

We are primarily a research laboratory but have close clinical links, with both the MPS and metabolic disease patients and neurosurgical patients.

Image: Lentiviral transduced eGFP positive GL-261 glioma tumour cells implanted orthotopically into the brains of C57BL/6 mice, demonstrating the infiltrative component of microglia in the brain tumour microenvironment. Green: eGFP expressing GL261 cells, Red: Iba-1 microglia/macrophages, Blue: DAPI nuclear stain

News

• Position statement on outcome of high dose genistein trial in Sanfilippo disease
• Ed Wraith Memorial meeting - Manchester, UK - 5th April 2014
• Clinical Trial announcement for high dose genistein in Sanfilippo disease - GENISiS2013 (PDF, 174 KB)
• Position Statement on the use of genistein to treat Sanfilippo disease (Mucopolysaccharidosis type IIIA-D) (PDF, 44 KB)
• MPS Stem Cell Lab Newsletter: Issue 1 (PDF, 196 KB)
• MPS Stem Cell Lab Newsletter: Issue 2 (PDF, 2 MB)

Media

2014 - Videolinks

• Lysosomal Disease Group Patient Impact Study and video
• Promotional video - Jonah's Just Begun - Sanfilippo Syndrome - We can fight our childrens fate
• Documentary - La Caixa and Xavi Hernandez - Raising awareness on gene therapy for Sanfilippo Disease -Spanish

Group Members and Affiliated Staff

• Dr Simon Jones - Consultant, Head of Willink Biochemical Genetics Unit
• Dr Rob Wynn - Consultant, Head of Bone Marrow Transplantation Unit
• Dr Becki Holley - Senior Postdoctoral Associate
• Dr Claire O'Leary - Postdoctoral Associate
• Dr Stuart Ellison -Postdoctoral Associate
• Mr Kenny Yu - Speciality Registrar Neurosurgery/PhD student
• Mr Ricky Pal -Speciality Registrar ENT/MD student
• Miss Ai Yin Liao - Research Technician/part time PhD
• Miss Helen Parker -PhD Student
• Mr Saam Yoshani - PhD Student
• Miss Helene Gleitz - PhD Student

Collaborators

Manchester

• Dr Cathy Merry, University of Manchester. Heparan sulphate and cellular interactions in neurodegenerative diseases
• Dr Maria Canal, University of Manchester. Circadian profiling in MPS disease
• Dr James Fildes, University of Manchester. Immunology in lysosomal disease
• Professsor Nancy Rothwell, University of Manchester. Microglial interactions with brain tumours
• Mr Ian Kamaly and Mr Omar Pathmanaban - Neurosurgery, Salford Royal NHS Foundation Trust. Brain tumour treatment development
• Imagen Biotech Ltd

International

• Professor Adrian Thrasher and Professor Bobby Gaspar, UCL. Stem cell gene therapy for lysosomal diseases
• Professor Frits Wijburg, AMC Amsterdam. Biomarker development for lysosomal diseases
• Professor Alexey Pshezhetsky, Sainte Justine Children's Hospital, Montreal, Canada. Gene therapy for MPSIIIC

Job Opportunities

We offer laboratory placements for motivated high quality project students on Manchester University Medical undergraduate or postgraduate MSc and MRes courses and will consider self-funded internships for excellent non-clinical or clinical candidates wishing to gain laboratory experience in the field.

Funded posts are advertised on the University jobsite and national websites such as www.jobs.ac.uk

American Society of Gene & Cell Therapy

The European Society of Gene & Cell Therapy

The British Society for Gene & Cell Therapy

The European Study Group on Lysosomal Diseases

The Brains for Brain European Network

Neuroscience Research Institute

The Manchester Tissue Regeneration & Stem Cell Network

2013 - Videolinks - Rare Disease Report

• Announcement of a phase III clinical trial for high dose genistein in Sanfilippo disease
• Review of the evidence for a clinical trial of high dose genistein in Sanfilippo disease
• Clinical trial for Genistein in Sanfilippo
• Mucopolysaccharidosis I (Hurler) disease and the animal model
• Stem Cell & Neurotherapy lab treatment strategies for Sanfilippo disease
• The role of HS in Mucopolysaccharidosis I (Hurler disease)
• The role of charities in funding rare disease work
• Collaboration between patient advocates and researchers

2012 - Videolinks

• Al Jazeera, Inside Story - Should Scientists be Playing God?
• BBC North - Jack Baird Raising awareness and funding for a clinical trial of Sanfilippo in Manchester
• BBC North West Tonight - Live Interview

Main Areas of Expertise

• Lysosomal disease model characterisation and treatment

• Stem cell biology and treatment of primary brain tumours

• Haematopoetic stem cell gene therapy and tolerance induction

• Haematopoietic cell migration and interactions within bone marrow and neurological niches

• Clinical translation of gene and cell therapies

Funders

The laboratory is funded by a programme grant and subsidiary grants from the https://mpssociety.org.uk/ to Dr Bigger

We gratefully acknowledge past and present funders including: The Norah Al Balla foundation, Great Ormond Street Research Chraity, Action Medical Research, Jonah's Just Begun, The Lady Shauna Gosling Trust, The Sanfilippo Children's Research Foundation (Canada), The Ollie G Ball,The National MPS Society (US), The Irish MPS society,  The Children's Bone Marrow Trust, BBSRC, The Manchester Biomedical Research Centre, Department of Health, CMFT NHS trust endowments, The Association for Glycogen Storage Disorders, The Brain Tumour Charity, The GEM appeal, Lois Gosling,

as well as contributions from the MPS societies of Austria, Canada, Germany, Ireland, Japan, Netherlands, Spain, Sweden, Switzerland, UK and USA.