Dr. David E. Nelson earned his B.Sc. in Biochemistry and his Ph.D. at the University of Liverpool in the United Kingdom. This was followed by post-doctoral training at Harvard Medical School, Dept. of Systems Biology and the University of Cambridge, Dept. of Pathology. He is interested in how macrophage polarization and antimicrobial function is regulated during pulmonary infections with the pathogenic yeast, Cryptococcus neoformans. His lab is currently focused on i) the role played by the CITED family of transcriptional coregulators in controlling the expression of genes associated with the M1 polarization state, and ii) how intracellular C. neoformans infection impacts host macrophage metabolism. His lab studies these processes using a variety of experimental tools and techniques, which include live cell microscopy, molecular cloning, RNAsequencing-based transcriptome profiling, qRT-PCR, metabolic assays, and basic biochemical techniques.

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• Wiggins, D., Maxwell, J., and Nelson, D.E. (2024). Exploring the Role of CITED Transcriptional Regulators in the Control of Macrophage Polarization. Frontiers in Immunology. 15, (April 4th, 2024)
• Leander, R., Owanga, G., Nelson, D. E., and Liu, Y. (2024). A Mathematical Model of Stroma-Supported Allometric Tumor Growth. Bulletin of Mathematical Biology. 86, (March 6th, 2024) 38.
• Subramani, A., *Hite, M. E. L., Garcia, S., Maxwell, J., *Kondee, H., *Millican, G. E., McClelland, E. E., Seipelt-Thiemann, R. L., and Nelson, D. E. (2023). Regulation of Macrophage IFNγ-Stimulated Gene Expression by the Transcriptional Coregulator CITED1. Journal of Cell Science. (Jan. 2023).
• Leander, R. N., Wu, Y., Ding, W., Nelson, D. E., Sinkala, Z. (2021). A model of the innate immune response to SARS-CoV-2 in the alveolar epithelium. Royal Society Open Science, 8: 210090. PMID: 34430043
• Subramani, A., Griggs, P., Frantzen, N., Mendez, J., Tucker, J., Murriel, J., Sircy, L. M., Millican, G. E., McClelland, E. E., Seipelt-Thiemann, R, L., Nelson, D. E. (2020). Intracellular Cryptococcus neoformans disrupts the transcriptome profile of M1- and M2- polarized host macrophages. PLOS ONE, 15(8): e0233818. DOI: 10.1371/journal.pone.0233818. PMID: 32857777
• Ghosh, R., Smith, S. A., Nwangwa, E. E., Arivett, B. A., Bryant, D. L., Fuller, M. L., Hayes, D., Bowling, J. L., Nelson, D. E., DuBois, J. D., Altman, E., Kline, P. C., Farone, A. L. (2019) Panax quinquefolius (North American ginseng) cell suspension culture as a source of bioactive polysaccharides: Immunostimulatory activity and characterization of a neutral polysaccharide AGC1. International Journal of Biological Macromolecules, Oct 15; 139:221-232. DOI: 10.1016/j.ijbiomac.2019.07.215. PMID: 31376448
• Rathje, C. C., Randle, S. J., Al Rawi, S., Skinner, B. M., Nelson, D. E., Majumdar, A., Johnson, E. E. P., Bacon, J., Vlazaki, M., Affara, N. A., Ellis, P. J., Laman, H. (2019). A Conserved Requirement for Fbxo7 During Male Germ Cell Cytoplasmic Remodeling. Frontiers in Physiology, 10;1278. DOI: 10.3389/fphys.2019.01278. PMID: 31649556
• Bowling, J. L., Skolfield, M. C., Riley, W. A., Nolin, A. P., Wolf, L. C., and Nelson, D. E. (2019). Temporal integration of mitochondrial stress signals by the PINK1:Parkin pathway. BMC Molecular and Cell Biology, 20; 33. DOI: 10.1186/s12860-019-0220-5. PMID: 31412778
• Nelson, R. H., and Nelson, D. E. (2018). Signal Distortion: How Intracellular Pathogens Alter Host Cell Fate by Modulating NF-κB Dynamics. Frontiers in Immunology, 14;9:2962. DOI: 10.3389/fimmu.2018.02962. PMID:30619320
• Guess, T., Lai, H., Smith, S. E., Sircy, L. M., Cunningham, K. D., Nelson, D. E., McClelland, E. E. (2018). Size Matters: Measurement of Capsule Diameter in Cryptococcus neoformans JoVE, URL: https://www.jove.com/video/57171 DOI:10.3791/57171. PMID: 29553511
• Park, H. S., Nelson, D. E., Taylor, Z. E., Hayes, J. B., Cunningham, K. D., Arivett, B. A., Ghosh, R., Wolf, L. C., Taylor, K. M., Farone, M. B., Handy, S. T., and Farone, A. L. (2017). Suppression of LPS-induced NF-κB Activity in THP-1 and RAW 264.7 Cell Lines by the Synthetic Aurone, SH9067. International Immunopharmacology vol. 43, p116-128. PMID: 27988459
• Hayes, J. B., Heusinkveld, L. E., Ding, W., Leander, R. N., McClelland, E. E., and Nelson, D. E. (2016). Modulation of Macrophage Inflammatory NF-κB Signaling by Intracellular Cryptococcus Neoformans. Journal of Biological Chemistry vol. 291, p15614-27. PMID: 27231343
• Randle, S. J., Nelson, D. E., Patel, P. S., and Laman, H. (2015). Defective Erythropoiesis in a Mouse Model of Reduced Fbxo7 Expression Due to Decreased p27 Expression. The Journal of Pathology. Doi: 10.1002/path.4571. PMID: 26095538
• 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

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Research area 1: Modulation of macrophage polarization by intracellular pathogens

Macrophages are innate phagocytic cells that act as a first line of defense against infection by numerous pathogens. The microbicidal activity of these cells is controlled in part by their polarization state, a series of temporary phenotypes defined by the differential expression of >1000 genes, that are adopted in response to microbial ligands and a variety of cytokines and chemokines produced by other immune cells. Perhaps unsurprisingly, many pathogens have evolved mechanisms to interfere with macrophage polarization as an immune evasion strategy, promoting their persistence within the host. As a model for this, we are investigating the effects of the human pathogen, Cryptococcus neoformans, a facultative intracellular yeast, on the polarization and gene expression of host macrophages. We also have a particular interest in the effects of intracellular C. neoformans on host cell NF-kappaB signaling and the role played by the CITED family of transcriptional co-regulators in shaping macrophage pro-inflammatory and antimicrobial gene expression. The overarching goal of my lab is to better understand how intercellular pathogens alter the activity of signaling pathways in host cells that control macrophage polarization. This research is currently supported by funds from the National Institutes of Health (NIAID 1R15AI178461-01) and was previously supported under (NIAID 1R15AI135826-01).

Relevant publications:

• Wiggins, D., Maxwell, J., and Nelson, D.E. (2024). Exploring the Role of CITED Transcriptional Regulators in the Control of Macrophage Polarization. Frontiers in Immunology. 15, (April 4th, 2024)
• Subramani, A., *Hite, M. E. L., Garcia, S., Maxwell, J., *Kondee, H., *Millican, G. E., McClelland, E. E., Seipelt-Thiemann, R. L., and Nelson, D. E. (2023). Regulation of Macrophage IFNγ-Stimulated Gene Expression by the Transcriptional Coregulator CITED1. Journal of Cell Science. (Jan. 2023).
• Subramani, A., Griggs, P., Frantzen, N., Mendez, J., Tucker, J., Murriel, J., Sircy, L. M., Millican, G. E., McClelland, E. E., Seipelt-Thiemann, R, L., Nelson, D. E. (2020). Intracellular Cryptococcus neoformans disrupts the transcriptome profile of M1- and M2- polarized host macrophages. PLOS ONE, 15(8): e0233818. DOI: 10.1371/journal.pone.0233818. PMID: 32857777
• Nelson, R. H., and Nelson, D. E. (2018). Signal Distortion: How Intracellular Pathogens Alter Host Cell Fate by Modulating NF-κB Dynamics. Frontiers in Immunology, 14;9:2962. DOI: 10.3389/fimmu.2018.02962. PMID:30619320
• Guess, T., Lai, H., Smith, S. E., Sircy, L. M., Cunningham, K. D., Nelson, D. E., McClelland, E. E. (2018). Size Matters: Measurement of Capsule Diameter in Cryptococcus neoformans JoVE, URL: https://www.jove.com/video/57171 DOI:10.3791/57171. PMID: 29553511
• Hayes, J. B., Heusinkveld, L. E., Ding, W., Leander, R. N., McClelland, E. E., and Nelson, D. E. (2016). Modulation of Macrophage Inflammatory NF-κB Signaling by Intracellular Cryptococcus Neoformans. Journal of Biological Chemistry vol. 291, p15614-27. PMID: 27231343

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Research area 1: Mitochondrial quality control

The PINK1:Parkin mitophagy pathway is a highly conserved mitochondrial quality control system that is responsible for identifying damaged, depolarized mitochondria and marking them for autophagic destruction before they can compromise the health and integrity of the broader mitochondrial network or the cell itself. The activity of the pathway appears especially important in the central nervous system as loss-of-function mutations in the genes encoding PINK1 and Parkin are associated with juvenile onset autosomal recessive forms of Parkinson’s disease, a neurodegenerative disorder that typically manifests in the elderly. The overarching goal of my lab is to better understand how the PINK1:Parkin pathway responds to different levels of mitochondrial stress, as might occur in aging cells, and successfully targets only irretrievably damaged mitochondria for destruction.

Relevant publications:

Bowling, J. L., Skolfield, M. C., Riley, W. A., Nolin, A. P., Wolf, L. C., and Nelson, D. E. (2019). Temporal integration of mitochondrial stress signals by the PINK1:Parkin pathway. BMC Molecular and Cell Biology, 20; 33.

Research area 2: Modulation of macrophage polarization by intracellular pathogens

Macrophages are innate phagocytic cells that act as a first line of defense against infection by numerous pathogens. The microbicidal activity of these cells is controlled in part by their polarization state, a series of temporary phenotypes defined by the differential expression of >1000 genes, that are adopted in response to microbial ligands and a variety of cytokines and chemokines produced by other immune cells. Perhaps unsurprisingly, many pathogens have evolved mechanisms to interfere with macrophage polarization as an immune evasion strategy, promoting their persistence within the host. As a model for this, we are investigating the effects of the human pathogen, Cryptococcus neoformans, a facultative intracellular yeast, on the polarization and gene expression of host macrophages. We also have a particular interest in the effects of intracellular C. neoformans on host cell NF-kappaB signaling. The overarching goal of my lab is to better understand how intercellular pathogens alter the activity of signaling pathways in host cells that control macrophage polarization. This research is currently supported by funds from the National Institutes of Health (NIAID 1R15AI135826-01).

Relevant publications:

Subramani, A., Griggs, P., Frantzen, N., Mendez, J., Tucker, J., Murriel, J., Sircy, L. M., Millican, G. E., McClelland, E. E., Seipelt-Thiemann, R, L., Nelson, D. E. (2020). Intracellular Cryptococcus neoformans disrupts the transcriptome profile of M1- and M2- polarized host macrophages. PLOS ONE, 15(8): e0233818.

Nelson, R. H., and Nelson, D. E. (2018). Signal Distortion: How Intracellular Pathogens Alter Host Cell Fate by Modulating NF-κB Dynamics. Frontiers in Immunology, 14;9:2962.

Hayes, J. B., Heusinkveld, L. E., Ding, W., Leander, R. N., McClelland, E. E., and Nelson, D. E. (2016). Modulation of Macrophage Inflammatory NF-κB Signaling by Intracellular Cryptococcus Neoformans. Journal of Biological Chemistry vol. 291, p15614-27.

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