Dr Tennore Ramesh, DVM, PhD
Department of Neuroscience
Sheffield Institute of Translational Neuroscience
385a Glossop Road
United Kingdom, S10 2HQ
Tel: 0114 22 22246
Amyotrophic lateral sclerosis/Motor neuron disease (ALS/MND) is an adult onset motoneuron degenerative disease with a lifetime risk of ~1/1000. Approximately 80% of the cases are fatal within five years of diagnosis. There is no cure and only one FDA approved therapy, Riluzole has a minor effect on the progression of the disease. Mutations in genes such as SOD1, TDP-43, FUS, ANG, and VAPB also cause some forms of ALS although most forms of ALS is sporadic in nature. Despite the identification many genes causing ALS the exact mechanism of motor neuron toxicity is unclear, although a variety of mechanisms have been postulated. Identifying the upstream events that result in toxicity is critical to impact the disease process. Protein misfolding and cellular inclusions are a common theme in many neurodegenerative diseases including ALS. How protein misfolding contributes to toxicity, if protein inclusions are protective or detrimental is presently unknown. In most cases the accumulation of mutant proteins are not universally present in all cells but are restricted to specific cell types and also to specific regions in the CNS affected in the disease. Understanding the cause and mechanism of this toxic process is one of the focuses of my research. To understand 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 ALS 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 ALS with mutation in the sod1 gene. Transgenic sod1 zebrafish carrying mutant sod1 develop disease that is similar to that seen in mice and human. Additionally, these transgenic fish show early embryonic readout of mutant sod1 induced cellular stress response as early as 24 hours post-fertilization allowing us to study disease in these microscopic stages.
Research projects available:
Items of Esteem:
Principal Funding Sources:
Tennore Ramesh, Alison N. Lyon, Ricardo H. Pineda, Chunping Wang, Paul M. L. Janssen, Benjamin D. Canan, Arthur H. M. Burghes and Christine E. Beattie. 2010. A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease. DMM. May 26. [Epub ahead of print]
Scott S, Kranz JE, Cole J, Lincecum JM, Thompson K, Kelly N, Bostrom A, Theodoss J, Al-Nakhala BM, Vieira FG, Ramasubbu J, Heywood JA. Design, power, and interpretation of studies in the standard murine model of ALS. Amyotroph Lateral Scler. 2008; 9(1):4-15. Authorship withdrawn.
Perjesi P, Kim T, Zharikova AD, Li X, Ramesh T, Ramasubbu J, Prokai L. 2003. Determination of clodronate content in liposomal formulation by capillary zone electrophoresis. J Pharm Biomed Anal.; 31(5):929-35.
Clark JE, Brennan A, Ramesh TM, Heywood JA. 2002. Novel trends in orphan market drug discovery: amyotrophic lateral sclerosis as a case study. Front Biosci.; 7:c83-96.
Janson CG, Ramesh TM, During MJ, Leone P, Heywood J. 2001. Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis. J Hematother