Despite the identification of several genes causing MND the exact mechanism of motor neuron toxicity is unclear. The role of protein misfolding and cellular inclusions is a common theme in many neurodegenerative diseases including MND. The focus of my research is:
- Identifying the upstream events in MND that result in toxicity.
- How protein misfolding contributes to toxicity, whether protein inclusions are protective or detrimental is presently unknown. In most cases the accumulation of mutant proteins is not universally present in all cells but is restricted to specific cell types and also to specific regions in the CNS affected in the disease. To understand the disease process in this complex environment requires complex systems such as mice and more recently zebrafish.
- My lab utilises the power of mice and fish to study the pathogenic processes involved in neuronal death. Many transgenic models of MND have been developed and have given valuable insight into the cellular players involved in disease process. My lab recently developed a transgenic zebrafish model of MND with mutation in the sod1 gene. Transgenic sod1 zebrafish carrying mutant sod1 develop disease that is similar to that seen in mice and humans. Additionally, these transgenic fish show an early embryonic readout of mutant sod1 induced cellular stress response, as early as 24 hours post-fertilization, allowing us to study very early disease mechanisms.
Since joining in 2009, I have supervised the research training of 2 BMedSci and MSc students and I am currently supervising 4 PhD students.
Dr Ramesh is a Lecturer in Translational Neuroscience. He is currently funded by three successful grant applications from the Sheffield Hospital Charitable Trust, the Thierry Latran Foundation and the MND Association. Dr Ramesh has been working in translational medicine right from the early days of his career and has led a major multidisciplinary programme of research in identifying new therapeutics for MND. He has recently developed a zebrafish model of MND and his group is using this model to identify early events of cellular stress that occur before disease symptoms are observed. He has identified a novel readout of cellular stress in the zebrafish MND model. His team uses a variety of approaches aiming to; 1. Identify cell specific changes in spinal neurons that lead to neuronal stress; 2. Develop high throughput screening to identify disease modifying genes and drugs; 3. Develop a new zebrafish model of TDP 43 related MND; and 4. Validating hits from zebrafish in the mouse models of MND.
Dr Ramesh recently published the zebrafish model of MND in 2010. He has multiple publications and patents to his credit. He was on the scientific advisory board of the Western ALS clinical trial group, San Francisco, USA and served as scientific advisor to several non-profit ALS groups. He serves as reviewer for multiple journals and international grant awarding agencies.
Dr Ramesh research is funded by the Sheffield Hospital Charitable Trust, the Thierry Latran Foundation and the MND Association.
2013-2014: Study of MS type inflammation on neuronal stress and C9ORF72 aggregation. Funding from Sheffield Teaching Hospital Research Grant. £59,567.
2013: PrioNet Startup funding: Discovery of effects of anti-prion compounds in sod1 zebrafish model of ALS. £10,000. Completed. Initiate new grant based on preliminary data.
2011: Motor Neuron Disease Association: £195000. Identification of progressive neuronal stress from early development to adulthood and utilization of this readout in a pharmacological screen for disease modifiers in the sod1 zebrafish model of ALS/MND. 2011-2014.
Rose tree trust has supported MNDA for this project and MNDA has already raised over half of the funding amount for this grant and has served as a good project for seeking funding for MNDA.
2010:Sheffield Hospital Charitable trust PhD studentship: £63,370: Zebrafish MND model as a tool for drug screening. 2010-2013
2011-2012: Foundation Thierry Latran: £30000. Transgenic zebrafish model of MND in drug discovery. 2010. Completed 2011.
Members of Research Group:
- Dr. Niki Panagiotaki, PhD: Post doctoral scientist
- Dr. Alexander McGown: Post doctoral scientist
- Mr. Matthew Shaw: PhD Student : Primary supervisor
- Damien Farhad: BMedSci student
- Alexander McGown: PhD student : Primary Supervisor
- Dr. Channa Hewamadduma: PhD student: Co supervisor
- Natasha Redhead: BMedSci student
- Jenny Hosty, BMedSci Student
- Sufana Al Mashhadi: MSc Molecular Neuroscience
- Marc Da Costa: PhD Student: Co supervisor
- Adil Seytanoglu: PhD student: Co supervisor
- Sumona Dhara: MSc in Stem Cell and Regenerative Medicine
- Fabiola Sica: MSc Molecular Neuroscience
Robyn A Grant, Paul S Sharpb, Aneurin J Kennerley, Jason Berwick, Andy Grierson, Tennore Ramesh*, Tony J Prescott*. 2014. Abnormalities in whisking behaviour are associated with lesions in brain stem nuclei in a mouse model of amyotrophic lateral sclerosis. Behavioral Brain Research. 259:274-83. Joint last authors
Marc M.J. Da Costa, Claire E. Allen, Adrian Higginbottom, Tennore Ramesh, Pamela J. Shaw and Christopher J. McDermott. 2014. A new zebrafish ENU model of SOD1 ALS replicates key features of the disease and represents a useful tool for therapeutic screening. Dis Model Mech. 7(1):73-81
Anna L Chapman, Ellen J Bennett, Tennore M Ramesh, Kurt J De Vos, Andrew J Grierson.2013 Axonal transport defects in a mitofusin 2 loss of function model of Charcot-Marie-Tooth disease in zebrafish. PLOS One. 8(6):e67276.
Channa A A Hewamadduma, Andrew J Grierson, Taylur P Ma, Luyuan Pan, Cecilia B Moens, Philip W Ingham, Tennore Ramesh, Pamela J Shaw. 2013. Tardbpl splicing rescues motor neuron and axonal development in a mutant tardbp zebrafish. Human Mol Gen. Mar 3. [Epub ahead of print] .
Alexander McGown, Jonathan R. McDearmid, Niki Panagiotaki, Huaxia Tong, Sufana Al Mashhadi, Natasha Redhead, Alison N. Lyon, Christine E. Beattie, Pamela J. Shaw, and Tennore M. Ramesh. 2012. Early Interneuron Dysfunction in ALS: Insights from a Mutant sod1 Zebrafish Model. Annals of Neurology. Oct 1. doi: 10.1002/ana.23780. [Epub ahead of print].
Ramesh T, Lyon AN, Pineda RH, Wang C, Janssen PM, Canan BD, Burghes AH, Beattie CE. 2010. A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease. Dis. Models. Mech. (9–10):652–62.
Tennore Ramesh is a well rounded scientist with widespread experience in academia, as well as corporate and non-profit environments. He has over 14 years of in vivo experience in functional genomics, pharmacology, and toxicology of drug development. Dr Ramesh graduated in Veterinary Medicine in the top 5 percentile from Madras Veterinary College, India. He was awarded a fully funded Graduate Research Fellowship to study in the USA and graduated with a PhD in microbiology and immunology from the University of Kentucky, Lexington, USA. He did his post-doctoral fellowship at the Ohio State University and the University of Michigan, Ann Arbor, USA which is within the top 15 ranked in the world. He went on to work in a biotechnology industry at CuraGen, a genomics company where he developed new genomic methods to identify drug efficacy and toxicity prior to entry into the market. When a family member was diagnosed with MND in 1999, he joined the ALS Therapy Development Foundation, Cambridge, USA. He was Instrumental in setting up the research program and served as the Founding scientist and Chief Scientific Officer from inception until 2003. The personal story of the origin and the journey of the foundation to a world class non-profit biotechnology company are showcased in the Sundance Film festival nominated documentary “So Much So Fast”. Due to the limitations of the mouse model and recognising the need for more basic science driven translational research, he moved again to the Ohio State University to develop the zebrafish model of MND. The sod1 model of MND is the first adult onset neurodegenerative disease model in zebrafish and was featured in this Issue of the journal “Disease Models and Mechanisms”. He relocated to Sheffield in August 2009, on hearing about the inauguration of the innovative high tech Sheffield Institute for Translational Neuroscience, SITraN to contribute further to MND research.
- Dec 2008-Present Non-Clinical Lecturer, Academic Neurology, University of Sheffield, UK.
- 2004-2008 Founder, PALS Fund for ALS Drug Discovery, Ohio State University. Research scientist, Ohio State University, Columbus, OH
- 2000-8/2003 Founding Scientist and Chief Scientific Officer, ALS-TDF, Newton, MA, USA
- 1999- 2000 Scientist, Toxico and Pharmacogenomics, CuraGen Corporation, New Haven, CT, USA
- 1998-1999 Post-Doctoral Research Fellow, Human Genetics, University of Michigan, Ann Arbor, MI, USA
- 1996-1998 Post-Doctoral Research Fellow, Neurobiotechnology Center, Ohio State University, Columbus, OH, USA
- 1992-1996 PhD, Microbiology and Immunology, University of Kentucky, Lexington, KY, USA
- 1990-1992, MS, Animal Sciences, University of Kentucky, Lexington, KY
- 1982-1988 B.V.Sc (D.V.M), Madras Veterinary College, India
Items of Esteem:
- Invited member: International Consortium on SOD and ALS (ICOSA)
- 2003-2006 Scientific Advisory Board, Western ALS study group (WALS)
- 1998 NIH Reproductive sciences training grant fellowship
- 1996 NIH Neuropharmacology training grant Fellowship
- 1995 Best Poster award, Graduate student research day
- 1990 Graduate school Fellowship
University of Sheffield
Faculty of Medicine, Dentistry and Health
Department of Neuroscience
Sheffield Institute for Translational Neuroscience
385a Glossop Road
United Kingdom, S10 2HQ
T: +44 (0)114 22 22246