Erik Russell Nelson
Assistant Professor of Molecular and Integrative Physiology
Cell-Cell Interactions, Drug Discovery, Endocrinology, Metabolic Regulation, Regulation of Gene Expression, Signal Transduction
2002 B.Sc. in Zoology, University of Calgary, Canada
2008 Ph.D. in Comparative Endocrinology, University of Calgary, Canada
2008-2014 Postdoctoral Associate, Duke University School of Medicine, Durham, NC.
Endocrine and Metabolic Control of Breast and Ovarian Cancer Pathophysiology
Breast cancer remains the most commonly diagnosed cancer among women, while ovarian cancer continues to have a very poor 5 year survival rate. The magnitude of this problem provides a strong impetus for studies that may lead to new chemopreventative strategies and/or lifestyle changes that reduce morbidity from these cancers. Therefore, the goal of our research is to elucidate the effects of the endocrine system and metabolism on breast and ovarian cancer initiation and progression. We integrate our expertise in physiology, endocrinology, immunology and in vivo models to pursue translational breast and ovarian cancer research.
Several studies have demonstrated correlations between obesity and increased breast cancer risk, and decreased progression free survival amongst ovarian cancer patients. Interestingly, it has also been observed that elevated cholesterol itself is a poor prognostic for these cancers, independent of body mass index. This puts into perspective the recent finding that a primary metabolite of cholesterol, 27-hydroxycholesterol, has the ability to activate the estrogen receptor. Estrogen and its receptor (ER) are well known to influence certain types of breast cancer. We have also shown that 27-hydroxychoelsterol can activate the Liver X Receptors (LXRs), adding another layer of complexity to its biological actions. Using several cellular and animal models, we have now shown that in animal models 27-hydroxycholesterol decreases the time to breast cancer onset, increases tumor growth rate, and increases metastasis. Importantly, tumor growth rate can be reduced by inhibiting cholesterol synthesis with drugs like statins, or by novel inhibitors of the enzyme responsible for the synthesis of 27-hydroxycholesterol, potentially providing novel therapeutic options for breast cancer patients.
The major focuses of the lab are:
Establishing 27-hydroxycholesterol as a causal link between obesity, hypercholesterolemia and breast cancer metastasis.
Defining the mechanisms by which 27-hydroxychoelsterol increases metastasis.
Determining the impact of cholesterol and its metabolites on ovarian cancer progression.
Delineating the role of nuclear receptor signaling within the tumor microenvironment and its impact on tumor progression.
2013 National Cancer Institute of the National Institutes of Health K99/R00 Pathway to Independence Award.
2013 Robert J. Fitzgerald Academic Achievement Award. Department of Pharmacology and Cancer Biology, Duke University School of Medicine.
2012 The Endocrine Society Award for Outstanding Paper in Endocrinology for 2011.
2011 Robert J. Fitzgerald Scholar Award: Outstanding publication in the Department of Pharmacology and Cancer Biology, Duke University Medical Center.
2011 The Endocrine Society Outstanding Abstract Award. ENDO2011, the annual Endocrine Society Meeting.
2010 Keystone Symposia Scholarship (Outstanding Abstract), Nuclear Receptors: Signalling, Gene Regulation and Cancer.
2009 Department of Defense Breast Cancer Research Program Postdoctoral Fellowship Award.
2008 Government of Alberta Queen Elizabeth II Graduate Scholarship.
Baek A.E. and Nelson E.R. (2016). The Contribution of Cholesterol and Its Metabolites to the Pathophysiology of Breast Cancer. Invited Review. Hormones and Cancer. 7(4):219-28. PMID: 27020054.
Nelson E.R., Wardell S.E., Jasper J.S., Park S., Suchindran S., Howe M.K.,Carver N.J., Pillai R.V., Sullivan P.M., Sondhi V., Umetani M., Geradts J., and McDonnell D.P. (2013). 27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology. Science. 342(6162):1094-8. PMID: 24288332.
McDonnell D.P., Park S., Goulet M.T., Jasper J.S., Wardell S.E., Chang CY, Norris J.D., Guyton J.R. and Nelson E.R. (2014). Obesity, Cholesterol Metabolism and Breast Cancer Pathogenesis. Cancer Research. 74(18): 4976-82. PMID: 25060521.
Wardell S.E., Nelson E.R., and McDonnell D.P. (2014). From empirical to mechanism based discovery of clinically useful ER ligands. Steroids. 90:30-8. PMID: 25084324.
Wardell S.E., Nelson E.R., Chao C.A., and McDonnell D.P. (2013). Bazedoxifene exhibits antiestrogenic activity in animal models of tamoxifen resistant breast cancer; implications for treatment of advanced disease. Clinical Cancer Research. 1;19(9):2420-31. PMCID: PMC3643989.
Nelson E.R., Wardell S.E., and McDonnell D.P. (2013). The Molecular Mechanisms Underlying the Pharmacological Actions of Estrogens, SERMs and Oxysterols: Implications for the Treatment and Prevention of Osteoporosis. Bone. 53:42-52. PMCID: PMC3552054.
Jones L.W., Antonelli J., Masko E.M., Lascola C.D., Fels D., Dewhirst M.W., Dyck J.R.B., Nagendran J., Flores C.T., Betof A.S., Young M.E., Nelson E.R., Pollak M., Broadwater G., and Freedland S.J. (2012) Exercise Modulation of the Host - Tumor Interaction in an Orthotopic Model of Murine Prostate Cancer. Journal of Applied Physiology. 113(2):263-72. PMCID: PMC3404704
Nelson E.R., DuSell C.D., Wang X., Howe M.K., Evans G., Michalek R.D., Rathmell J.C., Khosla S., Gesty-Palmer D., and McDonnell D.P. (2011). The oxysterol, 27-hydroxycholesterol, links cholesterol metabolism to bone homeostasis through its actions on the estrogen and liver X receptors. Endocrinology. 152(12): 4691-705. PMCID: PMC3230052.
Michalek R.D., Gerriets V.A., Nichols A.G., Inoue M., Kazmin D., Chang C-Y, Dwyer M., Nelson E.R., Pollizzi K.N., Ilkayeva O., Giguere V., Zuercher W.J., Powell J.D., Shinohara M.L., McDonnell D.P., Rathmell J.C. (2011). Estrogen Related Receptor-α is a Metabolic Regulator of Effector T cell Activation and Differentiation. Proceedings of the National Academy of Sciences of the United States of America. 108(45): 18348-53. PMCID: PMC3215012
DuSell C.D., Nelson E.R., Wang X., Abdo J., Mödder U.L., Umetani M., Gesty-Palmer D., Javitt N.B., Khosla S., McDonnell D.P. (2010). The Endogenous Selective Estrogen Receptor Modulator 27-hydroxycholesterol is a Negative Regulator of Bone Homeostasis. Endocrinology. 151(8): 3675-85. PMCID: PMC2940523
DuSell C.D., Nelson E.R., Wittmann B.M., Fretz J.A., Kazmin D., Thomas R.S., J. Pike W., and McDonnell D.P. (2010). Regulation of aryl hydrocarbon receptor function by Selective Estrogen Receptor Modulators. Molecular Endocrinology. 24(1): 33-46. PMCID: PMC2802893