Dr. David E. Nelson
Office: DSB 120A
Campus Mailing Address: MTSU Box 60, Murfreesboro, TN 37132
2002 - B.Sc, Applied Biochemistry, University of Liverpool, UK
2006 - PhD, Biological Sciences (Cell Biology), University of Liverpool, UK
2006-2008 – Dept. of Systems Biology, Harvard Medical School, Boston, MA
2008-2013 - Dept. of Pathology, University of Cambridge, UK
BIOL 6270 – Cell Metabolism and Human Disease
Cell and Molecular Biology, Signal Transduction, Neurodegeneration and Cancer
Cells within the human body are constantly exposed to a myriad of biochemical signals, pushing them to grow, divide or even undergo programmed cell death (apoptosis). How do cells exposed to so many different and often contradictory signals decide what to do? They use a complicated internal network of receptors, kinases and transcription factors, arranged in pathways that effectively perform a biological computation, integrating these signals and arriving at an appropriate cell fate decision.
There is now an increasing awareness that the behavior or dynamics of these pathways is an important part of the decision making process. For instance the NF-κB and p53 pathways do not merely switch on or off in response to stimulus but can oscillate or pulse. These behaviors emerge from the way these pathways are 'wired', the feedback relationships that exist between the components of the pathway. Pathogenic mutations that compromise the function of components or regulators of these pathways could alter their behavior and in so doing push the cell towards an inappropriate fate; for example, excessive proliferation in the case of cancer or inappropriate cell death in the case of a neurodegenerative disorder. Signaling pathways, like NF-κB, a potent regulator of anti-apoptotic and inflammatory genes, lie at the crossroads of these two opposing cell fates and has been implicated in both cancer and neurodegenerative disorders like Parkinson's disease (PD).
My lab is particularly interested in studying how the behavior of the NF-κB pathway is altered in PD. A number of the genes linked to heritable, early-onset forms of PD, known as PARK genes, have also been shown to regulate and in turn are regulated by NF-κB. We want to determine whether these putative feedback loops play a role in shaping the behavior of NF-κB signaling and how this is altered by pathogenic mutation. In so doing, we hope to develop new therapeutic strategies to restore normal signaling and combat PD.
Nelson, D. E., Randle, S. J., and Laman, H. (2013). Beyond ubiquitination: the atypical functions of Fbxo7 and other F-box proteins. Open Biology vol. 3, 130131
Burchell, V. S*., Nelson. D. E*., Sanchez-Martinez. A*., Delgado-Camprubi. M., Ivatt, R. M., Pogson, J. H., Randle, S. J., Wray. S., Lewis. P. A., Houlden. H., Abramov. A. Y., Hardy. J., Wood. N. W., Whitworth. A. J., Laman. H. and Plun-Favreau. H. (2013). The Parkinson's Disease Genes Fbxo7 and Parkin Interact to Mediate Mitophagy. Nat. Neurosci, vol. 9, p1257-65 (*Joint First Author)
Lomonosov. M., Meziane. el. K., Ye. H., Nelson. D. E., Randle. S. J. and Laman. H. (2011). Expression of Fbxo7 in haematopoietic progenitor cells cooperates with p53 loss to promote lymphomagenesis. PLoS One, vol. 6, e21165.
Nelson, D. E. and Laman, H. (2011). A Competitive Binding Mechanism Between Skp1 and Exportin 1 (CRM1) Controls the Localization of a Subset of F-box Proteins. Journal of Biological Chemistry, vol. 286, p19804-15.
Meziane. E. K., Randle. S. J., Nelson. D. E., Lomonosov. M. and Laman. H. (2011). Knockdown of Fbxo7 Reveals its Regulatory Roles in the Proliferation and Differentiation of Haematopoietic Precursor Cells. Journal of Cell Science, vol. 124, p2175-86.
Turner, D. A., Paszek, P., Woodcock, D. J., Nelson, D. E., Horton, C. A., Spiller, D. G., Rand, D. A., White, M. R. H. and Harper, C. V. (2010). Stochastic Dynamics of NF-kappB responses in single cells following low-dose TNFalpha stimulation. Journal of Cell Science vol. 123 p2834-43.
Ashall, L*., Horton, C. A*., Nelson, D. E*., Paszek, P., Harper, C. V., Sillitoe, K., Ryan, S., Spiller, D. G., Unitt, J. F., Broomhead, D. S., Kell, D. B., Rand, D. A., Sée, V. and White, M. R. (2009). Pulsatile Stimulation Determines Timing and Specificity of NF-kappaB-Dependent Transcription. Science vol. 324, p242-6. (*Joint-first author)
Shen, H., Nelson, G., Nelson, D. E., Kennedy, S., Spiller, D.G., Griffiths, T., Paton, N., Oliver, S. G., White, M. R. and Kell, D. B. (2006). Automated tracking of gene expression in individual cells and cell compartments. J R Soc Interface vol. 3, p787-94.
Shen, H., Nelson, G., Kennedy, S., Nelson, D. E., Johnson, J., Spiller, D.G., White, M. R. and Kell, D. B. (2006). Automated tracking of biological cells and compartments using particle filters and active contours. Chemometrics and Intelligent Laboratory Systems vol. 82, p276-82.
Barker, C. R., McNamara, A. V., Rackstraw, S. A., Nelson, D. E., White, M. R., Watson, A. J. and Jenkins, J. R. (2006). Inhibition of Hsp90 acts synergistically with topoisomerase II poisons to increase the apoptotic killing of cells due to an increase in topoisomerase II mediated DNA damage. Nucleic Acids Res vol. 34, p1148-57.
Nelson, D. E., Horton, C. A., Sée, V., Johnson, J. R., Nelson, G., Spiller, D. G., Kell, D. and White, M. R. (2005). Response to Comment on "Analyzing the Dynamic Behaviour of Negative Feedback in Cellular Signal Transduction". Science vol. 308, p52.
Nelson, D. E., Sée, V., Nelson, G. and White, M. R. (2004). Oscillations in transcription factor dynamics: a new way to control gene expression. Biochem Soc Trans vol. 32, p1090-2.
Nelson, D. E., Ihekwaba, A. E., Elliott, M., Johnson, J. R., Gibney, C. A., Foreman, B. E., Nelson, G., Sée, V., Horton, C. A., Spiller, D. G., Edwards, S. W., McDowell, H. P., Unitt, J. F., Sullivan, E., Grimley, R., Benson, N., Broomhead, D., Kell, D. B. and White, M. R. (2004). Oscillations in NF-kappaB signaling control the dynamics of gene expression. Science vol. 306, p704-8.