Dr Mark Cooper
Reader in Neurology
Clinical and Movement Neurosciences
UCL Queen Square Institute of Neurology
- Joined UCL
- 1st Aug 1998
Parkinson’s Disease (PD):My research focuses on elucidating the cell and molecular mechanisms underlying Parkinson’s disease. Over the past 20 years my research has focussed on the role of mitochondrial dysfunction in PD brains (Schapira et al 1990) and platelets (Krige et al 1994) and its relationship to other features detected in PD brains including ; mitochondrial DNA defects (Gu et al 1998 ), nitric oxide (Cleeter et al 1994), oxidative stress (Seaton et al 1997), iron (Hartley et al 1993) and cell death (Hartley et al 1994). Increasingly with the identification of the familial causes of PD my research has turned to the role of specific mutant genes in PD pathogenesis. Alpha-synuclein has been my main focus with additional interests in ; LRRK2 (Papkovskaia et al 2012), parkin (Gegg et al 2010) and glucocerebrosidase (Gegg et al 2012). While mitochondrial biochemistry is a recurrent theme I also have a broader interest including dopamine metabolism (Tabrizi et al 2000), protein degradation pathways (Alvarez-Erviti et al 2010), alpha-synuclein aggregation and transmission (Alvarez-Erviti et al 2011) and microRNA dysregulation (Alvarez-Erviti et al 2013).
Alpha-synuclein : alpha-synuclein pathology is at the core of PD. I am interested in the normal function of alpha-synuclein. I have a project investigating the regulation of S129 phosphorylation, (Chau et al 2009) and how it may affect its function.I am interested in the cellular handling of alpha-synuclein in particular the pathways of its degradation and how these may be affected in PD. We have identified a deficiency of hsc70 and LAMP2A proteins in PD brains (Alvarez-Erviti et al 2010) which may be responsible for the cellular increase in alpha-synuclein levels in PD. In addition we are studying what factors influence its; oligomerisation, aggregation and transmission of synuclein aggregates between cells and the role of exosomes in this process (Alvarez-Erviti et al 2011) . In collaboration with Lydia Alvarez I have a project investigating the role of microRNA dysregulation in PD and how this relates to other pathological findings. We have identified specific microRNAs that can regulate hsc70 and LAMP2A expression which are dramatically elevated in PD brains possibly explaining the observed changes (Alvarez-Erviti et al 2013). We are now investigating the mechanisms underpinning the microRNA dysregulation. I have a collaboration with Lydia Alvarez studying the potential of RVG modified exosome as an in vivo vehicle for the delivery of siRNAs to murine CNS to down-regulate alpha-synuclein. This is using various cell lines and the human S129D alpha-synuclein transgenic mouse model which shows alpha-synuclein aggregation. This is an exciting new system which has the potential to treat PD by preventing the increased alpha-synuclein aggregation and its transmission between neurons with disease progression.
I coordinate and lecture on: - BIOC3016 Genes to disease BSc and BIOCG016 MRES module. - BAMS 2003 Musculoskeletal and Neuroscience module
I coordinate and lecture on:
- BIOC3016 Genes to disease BSc and BIOCG016 MRES module.
- BAMS 2003 Musculoskeletal and Neuroscience module
-BAMS Neurogenetics to Neurodegeneration module
I supervise laboratory projects for BSc, MSc and MRES students on the
-Biochemistry, Biomedicine and Neuroscience BSc courses
-Clinical Neuroscience MSc
-Translational Neurology MRES
Supervise library projects for Clinical Neuroscience MSc
Run the 7130 double block Library Project SSC for Medical students
- Doctorate, Doctor of Philosophy | 1987
- University of Hull
- First Degree, Bachelor of Science (Honours) | 1983
My scientific training was in the field of mitochondrial biochemistry in disease under the supervision of John Morgan-Hughes and John Clark (PhD 1987) at the Institute of Neurology, London. I characterisation the defects in patients with mitochondrial disorders which led to the identification of the first mtDNA deletions (Holt et al 1988, 1989),
In 1990 I was appointed as Lecturer in the Department of Protein and Molecular Biology at the Royal Free Hospital Medical School, and subsequently in 1994 as Senior Lecturer in the department of Clinical Neurosciences. In 2010 I was appointed as Reader in Neurodegenerative diseases in the department of Clinical Neurosciences UCL Institute of Neurology.
Mitochondrial function continued to play an important role in my research, studying Leber’s hereditary Optic Neuropathy (Cock et al 1995) and various other mtDNA mutations (Morten et al 1993) and demonstrated mtDNA depletion syndrome was a nuclear gene disorder (Bodnar et al 1993). I generated an in vivo model to recapitulate the biochemical phenotypes (Cooper et al 1988) and therapeutic evaluation (Cooper et al 1992).
Mitochondrial function in neurodegenerative diseases continues to play a larg part of my research covering ;PD (Schapira et al 1989), Alzheimer’s disease (Cooper et al 1993), HD (Gu et al 1996), Friedreich's ataxia (Bradley et al 2000), Wilson’s disease (Gu et al 2000), ageing (Cooper et al 1992) ;oxidative stress (Thomas et al 1993, Rafique et al 2001) and increased iron (Hartley et al 1993).
Friedreich’s Ataxia (FRDA) research made up a significant part of my work.We confirmed the role of mitochondrial dysfunction, iron accumulation (Bradley et al 2000) and oxidative damage (Bradley et al 2004) in patients with FRDA. Using 31P MRS in collaboration with Raphaele Lodi we were able to detect the mitochondrial ox phos defects in vivo in skeletal muscle (Lodi et al 1999) and cardiac muscle (Lodi et al 2001). We obtained extensive clinical data on over 70 FRDA patients involving neurological, cardiac (Rajagopalan et al 2010), speech and limb co-ordination evaluations and evaluation of quality of life and activities of daily living for the cross sectional analysis of the natural history of FRDA (Cooper et al 2008). Long term vitamin E and coenzyme Q10 therapy trials identified an improvement in mitochondrial function (Lodi et al 2001, Hart et al 2005) and clinical scores (Cooper et al 2008). We have evaluated the ICARS scale for the evaluation of FRDA (Cano et al 2005, Metz et al 2013) and generated a new validated patient scale – Friedreich’s Ataxia Impact Scale (FAIS) (Cano et al 2009). I have collaborated with Mark Pook in the analysis of a transgenic mouse model (Pook et al 2001, Al-Mahdawi et al 2006).