Lisa Chakrabarti

Contact

• workRoom A55 School of Veterinary Medicine and Science
  Sutton Bonington Campus
  Sutton Bonington
  Leicestershire
  LE12 5RD
  UK
• work0115 951 6450
• fax0115 951 6440
• Lisa.Chakrabarti@nottingham.ac.uk
• http://www.nottingham.ac.uk/vet/people/lisa.chakrabarti

Biography

I received a BSc (Hons) in Zoology from the University of Leeds and went on to work with Kay Davies at the now David Weatherall Institute (IMM) to help decipher the molecular basis of X linked mental retardation. My research in this area led to a D.Phil in Biochemistry from the University of Oxford. Postdoctoral work took me to the USA to work with Leroy Hood in the Department of Biotechnology at the University of Washington in Seattle. A subsequent postdoctoral appointment was spent at the MRC Prion Unit at the University of London. In 2007 I was promoted to Research Assistant Professor in the Department of Laboratory Medicine at the University of Washington, Seattle where I established my current research interest in the molecular basis of neurodegeneration. In 2010 I was appointed Lecturer in Protein Biochemistry at the School of Veterinary Medicine and Science at the University of Nottingham.

Expertise Summary

My practical expertise includes mitochondrial complex assays, biochemical enzyme assays, recombinant protein production, primary neuron culture, retinal biology, comparative biology genes, transcripts and proteins.

I also have academic experience in

Genetics, gene identification and expression analyses in mental retardation and FTD3 dementia. Microarray analysis using gene ontology groups in dementia and ataxia. Mutation detection and characterisation of animal models of neurodegenerative disease. Genomics and genome-wide association studies in complex disease - Rheumatoid Arthritis and Prostate Cancer. Linkage analysis software development. Proteomics of complex mixtures by label free mass spec approaches and 2D gel electrophoresis. Lipidomics data analysis. Molecular pathway determination. Electron microscopy of neural tissues undergoing autophagy and mitophagy.

Teaching Summary

At undergraduate level I teach mostly within the neuroscience module. Other teaching includes biochemistry of proteins, cell biology, cell death, liver function and enzyme kinetics. I also supervise… read more

Research Summary

My current research interests focus upon understanding the molecular basis of neurodegeneration. The cost of managing neurodegenerative disease is currently calculated at EUR 72 billion annually.… read more

Selected Publications

• POLLARD A, SHEPHARD F, FREED J, LIDDELL S and CHAKRABARTI L, 2016. Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration. Aging. 8(10), 2425-2436

• View all publications

http://lisalabbook.blogspot.co.uk/

At undergraduate level I teach mostly within the neuroscience module. Other teaching includes biochemistry of proteins, cell biology, cell death, liver function and enzyme kinetics. I also supervise a number of undergraduate research projects - mostly in the areas of mitochondrial biology of ageing and degeneration. Working in the Vet school I have access to materials that allow comparisons between many different species at the protein and biochemical level.

Current Research

My current research interests focus upon understanding the molecular basis of neurodegeneration. The cost of managing neurodegenerative disease is currently calculated at EUR 72 billion annually. However, treatment for these disorders is limited, mostly consisting of perfunctory symptom control - often with undesirable side effects in both the short and long term. Risk of neurodegeneration for an individual increases with age, and the proportion of the European population aged over 65 is likely to rise to 25% by 2030 (from 16% today). Therefore, the incidence of these conditions, as well as the social and financial costs of treating them, is set to rise steeply in the coming years. Better strategies for prevention and treatment must be sought as a matter of urgency. Neurodegenerative diseases typically have a slow insidious onset and the course of disease is often lengthy.

We are using 'omics' technologies, together with imaging techniques to analyse the changes that occur in neurons which eventually lead to their demise. We have identified the importance of the protein NNA1/ CCP1 for cerebellar health and how genetic changes can alter the expression or stability of the protein. We have also looked using ultrastructural methods and found that a process known as autophagy is occurring in a dramatically different way in affected neurons when compared with normal brain. Much of what we have found appears to also apply to the degenerating retina such as is found in the human disease Retinitis Pigmentosa. Our findings using a model of neurodegenerative disease have provided detail in areas such as the involvement of mitochondria in these disorders. In the case of neurodegeneration it is difficult to gain a clear insight into presymptomatic disease and early events. Post mortem brain and retina provide only a snapshot of a ravaged tissue with elevated markers of cell death and inflammation. I am interested in studying the cusp of development to maturity gained in the neuron, revealing the cause of the disease process rather than the result. The retina degenerates more slowly in the majority of retinal disease processes in humans. By gathering data at a pre/early symptomatic stage we gain advantage over a tissue already depleted of affected neurons. Our studies allow the possibility of moving towards therapies that can be applied before neuronal loss leads to symptomatic disease, a far preferable approach than to try and repair the damage once disease has run its course.

Past Research

Previously I have been interested in finding and characterising genes responsible for mental retardation, developmental delay and dementia. I have also used methods of genetic linkage analysis to locate susceptibility loci for complex diseases such as prostate cancer, rhuematoid arthritis and diabetes. Characterisation of a classic, spontaneous model of neurodegeneration (Purkinje Cell Degeneration) has lead to an interest in the mitochondrial basis of disease and an analysis of the interplay between age and degenerative processes.

Future Research

My interest is heading towards a more complete understanding of the cellular organelle that is central to biological energy - the mitochondrion. We will be looking at normal mitochondrial biology, throughout the lifespan, in different species. We contrast what we see 'normally' with the situation in disease to understand the possibilities, flexibility and compensatory mechanisms in biological systems.

Defining the parameters within which an organism works best will allow us to achieve therapy and cure.

• STÖGER, REINHARD, WILLIAMS, PAULA, SHEPHARD, FREYA and CHAKRABARTI, LISA, 2017. Elevated 5hmC levels characterize DNA of the cerebellum in Parkinson's disease npj Parkinson's Disease. 3(1), 6
• POLLARD, AMELIA K, ORTORI, CATHARINE A, STOGER, REINHARD, BARRETT, DAVID A and CHAKRABARTI, LISA, 2017. Mouse mitochondrial lipid composition is defined by age in brain and muscle. Aging.
• SHEPHARD, FREYA, GREVILLE-HEYGATE, OLIVER, LIDDELL, SUSAN, EMES, RICHARD and CHAKRABARTI, LISA, 2016. Analysis of mitochondrial haemoglobin in Parkinson's disease brain Mitochondrion. 29, 45-52
• POLLARD, AMELIA KATE, CRAIG, EMMA LOUISE and CHAKRABARTI, LISA, 2016. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration PloS one. 11(6), e0157405
• POLLARD A, SHEPHARD F, FREED J, LIDDELL S and CHAKRABARTI L, 2016. Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration. Aging. 8(10), 2425-2436
• INGRAM T and CHAKRABARTI L, 2016. Proteomic profiling of mitochondria: what does it tell us about the ageing brain? Aging. 8(12), 3161-3179
• 2016. Defining a role for hemoglobin in Parkinson’s disease NPJ Parkinson's Disease.
• INGRAM, THOMAS and CHAKRABARTI, LISA, 2016. Proteomic profiling of mitochondria: what does it tell us about the ageing brain? AGING-US. 8(12), 3161-3179
• SHEPHARD F, GREVILLE-HEYGATE O, MARSH O, ANDERSON S and CHAKRABARTI L, 2014. A mitochondrial location for haemoglobins--dynamic distribution in ageing and Parkinson's disease. Mitochondrion. 14(1), 64-72
• LATHROP, M.J., CHAKRABARTI, L., ENG, J., RHODES, C.H., LUTZ, T., NIETO, A., LIGGITT, H.D., WARNER, S., FIELDS, J., STÖGER, R. and FIERING, S., 2010. Deletion of the Chd6 exon 12 affects motor coordination Mammalian Genome. 21(3-4), 130-142
• CHAKRABARTI, L., ZAHRA, R., JACKSON, S.M., KAZEMI-ESFARJANI, P., SOPHER, B.L., MASON, A.G., TONEFF, T., RYU, S., SHAFFER, S., KANSY, J.W., ENG, J., MERRIHEW, G., MACCROSS, M.J., MURPHY, A., GOODLETT, D.R. and HOOK, V., 2010. Mitochondrial dysfunction in NnaD mutant flies and Purkinje cell degeneration mice reveals a role for Nna proteins in neuronal bioenergetics Neuron. 66(6), 835-847
• CHAKRABARTI, L., ENG, J., IVANOV, N., GARDEN, G.A. and LA SPADA, A.R., 2009. Autophagy activation and enhanced mitophagy characterize the Purkinje cells of pcd mice prior to neuronal death. Molecular Brain. 2(1), 24
• CHAKRABARTI, L., ENG, J., MARTINEZ, R.A., JACKSON, S., HUANG, J., POSSIN, D.E., SOPHER, B.L. and LA SPADA, A.R., 2008. The zinc-binding domain of Nna1 is required to prevent retinal photoreceptor loss and cerebellar ataxia in Purkinje cell degeneration (pcd) mice Vision Research. 48(19), 1999-2005
• CHAKRABARTI, LISA, NEAL, JAMES T, MILES, MICHAEL, MARTINEZ, REFUGIO A, SMITH, ANNETTE C, SOPHER, BRYCE L and LA SPADA, ALBERT R, 2006. The Purkinje cell degeneration 5J mutation is a single amino acid insertion that destabilizes Nna1 protein. Mammalian genome : official journal of the International Mammalian Genome Society. 17(2), 103-10
• SKIBINSKI, GAIA, PARKINSON, NICHOLAS J, BROWN, JEREMY M, CHAKRABARTI, LISA, LLOYD, SARAH L, HUMMERICH, HOLGER, NIELSEN, JØRGEN E, HODGES, JOHN R, SPILLANTINI, MARIA GRAZIA, THUSGAARD, TOVE and BRAND, 2005. Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia. Nature genetics. 37(8), 806-8
• BROWN, JERRY, GYDESEN, SUSANNE, JOHANNSEN, PETER, GADE, ANDERS, SKIBINSKI, GAIA, CHAKRABARTI, LISA, BRUN, ARNE, SPILLANTINI, MARIA, YANCOPOULOU, DESPINA, THUSGAARD, TOVE, SORENSEN, ASGER and FISHER, ELIZ, 2004. Frontotemporal dementia linked to chromosome 3. Dementia and geriatric cognitive disorders. 17(4), 274-6
• YANCOPOULOU, DESPINA, CROWTHER, R ANTHONY, CHAKRABARTI, LISA, GYDESEN, SUSANNE, BROWN, JEREMY M and SPILLANTINI, MARIA GRAZIA, 2003. Tau protein in frontotemporal dementia linked to chromosome 3 (FTD-3). Journal of neuropathology and experimental neurology. 62(8), 878-82
• GYDESEN, S, BROWN, J M, BRUN, A, CHAKRABARTI, L, GADE, A, JOHANNSEN, P, ROSSOR, M, THUSGAARD, T, GROVE, A, YANCOPOULOU, D, SPILLANTINI, M G, FISHER, E M C, COLLINGE, J and SORENSEN, S A, 2002. Chromosome 3 linked frontotemporal dementia (FTD-3). Neurology. 59(10), 1585-94
• PETERS, M A, JARVIK, G P, JANER, M, CHAKRABARTI, L, KOLB, S, GOODE, E L, GIBBS, M, DUBOIS, C C, SCHUSTER, E F, HOOD, L, OSTRANDER, E A and STANFORD, J L, 2001. Genetic linkage analysis of prostate cancer families to Xq27-28. Human heredity. 51(1-2), 107-13
• GOODE, E L, STANFORD, J L, CHAKRABARTI, L, GIBBS, M, KOLB, S, MCINDOE, R A, BUCKLEY, V A, SCHUSTER, E F, NEAL, C L, MILLER, E L, BRANDZEL, S, HOOD, L, OSTRANDER, E A and JARVIK, G P, 2000. Linkage analysis of 150 high-risk prostate cancer families at 1q24-25. Genetic epidemiology. 18(3), 251-75
• XU, J, 2000. Combined analysis of hereditary prostate cancer linkage to 1q24-25: results from 772 hereditary prostate cancer families from the International Consortium for Prostate Cancer Genetics. American journal of human genetics. 66(3), 945-57
• GIBBS, M, STANFORD, J L, JARVIK, G P, JANER, M, BADZIOCH, M, PETERS, M A, GOODE, E L, KOLB, S, CHAKRABARTI, L, SHOOK, M, BASOM, R, OSTRANDER, E A and HOOD, L, 2000. A genomic scan of families with prostate cancer identifies multiple regions of interest. American journal of human genetics. 67(1), 100-9
• GIBBS, M, STANFORD, J L, MCINDOE, R A, JARVIK, G P, KOLB, S, GOODE, E L, CHAKRABARTI, L, SCHUSTER, E F, BUCKLEY, V A, MILLER, E L, BRANDZEL, S, LI, S, HOOD, L and OSTRANDER, E A, 1999. Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. American journal of human genetics. 64(3), 776-87
• PARMANTIER, E, LYNN, B, LAWSON, D, TURMAINE, M, NAMINI, S S, CHAKRABARTI, L, MCMAHON, A P, JESSEN, K R and MIRSKY, R, 1999. Schwann cell-derived Desert hedgehog controls the development of peripheral nerve sheaths. Neuron. 23(4), 713-24
• GIBBS, M, CHAKRABARTI, L, STANFORD, J L, GOODE, E L, KOLB, S, SCHUSTER, E F, BUCKLEY, V A, SHOOK, M, HOOD, L, JARVIK, G P and OSTRANDER, E A, 1999. Analysis of chromosome 1q42.2-43 in 152 families with high risk of prostate cancer. American journal of human genetics. 64(4), 1087-95
• CHAKRABARTI, L, BRISTULF, J, FOSS, G S and DAVIES, K E, 1998. Expression of the murine homologue of FMR2 in mouse brain and during development. Human molecular genetics. 7(3), 441-8
• CHAKRABARTI, L and DAVIES, K E, 1997. Fragile X syndrome. Current opinion in neurology. 10(2), 142-7
• RITCHIE, R J, CHAKRABARTI, L, KNIGHT, S J, HARDING, R M and DAVIES, K E, 1997. Population genetics of the FRAXE and FRAXF GCC repeats, and a novel CGG repeat, in Xq28. American journal of medical genetics. 73(4), 463-9
• KNIGHT, S J, RITCHIE, R J, CHAKRABARTI, L, CROSS, G, TAYLOR, G R, MUELLER, R F, HURST, J, PATERSON, J, YATES, J R, DOW, D J and DAVIES, K E, 1996. A study of FRAXE in mentally retarded individuals referred for fragile X syndrome (FRAXA) testing in the United Kingdom. American journal of human genetics. 58(5), 906-13
• CHAKRABARTI, L, KNIGHT, S J, FLANNERY, A V and DAVIES, K E, 1996. A candidate gene for mild mental handicap at the FRAXE fragile site. Human molecular genetics. 5(2), 275-82
• Exposure to the ROCK inhibitor fasudil promotes gliogenesis of neural stem cells in vitro Stem cell research. (In Press.)