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Nancie Jo MacIver, MD, PhD

Associate Professor of Pediatrics
Assistant Professor in Immunology
Assistant Professor in Pharmacology and Cancer Biology
Member of Duke Molecular Physiology Institute
Campus mail: 3000 Erwin Road, Suite 200, Durham, NC 27705
Phone: (919) 684-8289
Email address: nancie.maciver@duke.edu

My laboratory is broadly interested in how large changes in nutritional status (e.g. malnutrition or obesity) influence T cell immunity.  Malnutrition can lead to immunodeficiency and increased risk of infection, whereas obesity is associated with inflammation that promotes multiple diseases including autoimmunity, type 2 diabetes, and cardiovascular disease.  We have identified the adipocyte-secreted hormone leptin as a critical link between nutrition and immunity.  Leptin is secreted from adipocytes in proportion to adipocyte mass and is therefore decreased in malnutrition and increased in obesity.  We have found that leptin is a critical regulator of effector T cell glucose metabolism and thereby drives effector T cell activation.  From these initial findings, we have established further lines of investigation, as summarized here.

(1) Determining molecular mechanisms of T cell dysfunction in malnutrition – Our goal is to identify metabolic and epigenetic mechanisms by which malnutrition and decreased leptin alter T cell function leading to increased susceptibility to infection and protection against autoimmune diseases.  We study this using a mouse model of autoimmunity, experimental autoimmune encephalomyelitis (EAE).

(2) Elucidating mechanisms of T cell inflammation in obesity-induced type 2 diabetes – Our goal is to identify molecular and metabolic mechanisms by which obesity alters the Teff/Treg balance, resulting in inflammation and subsequent insulin resistance leading to type 2 diabetes.  With our collaborators from UNC Chapel Hill, we are also identifying immunometabolic changes in obese animals and humans that correlate with increased susceptibility to influenza.

(3) Determining the role of insulin and IGF-1 in regulating T cell function and metabolism – Our goal is to identify how insulin influences both T cell glucose uptake and T cell differentiation/cytokine production and determine the role of insulin signaling in T cells in the setting of obesity-associated diabetes.  We hypothesize that insulin has a direct role in T cell function through its abiltiy to alter T cell glucose metabolism, influence T cell cytokine production, and impact the pathophysiology of obesity-associated type 2 diabetes. 

Education and Training

  • Pediatric Endocrinology Fellowship, Pediatrics, Duke University, 2006 - 2009
  • Pediatrics Internship & Residency, Pediatrics, Duke University, 2003 - 2006
  • Ph.D., Mayo School of Health Sciences, 2003
  • M.D., Mayo School of Health Sciences, 2003

Publications

Schmidt, Elyse A., Brian E. Fee, Stanley C. Henry, Amanda G. Nichols, Mari L. Shinohara, Jeffrey C. Rathmell, Nancie J. MacIver, et al. “Metabolic Alterations Contribute to Enhanced Inflammatory Cytokine Production in Irgm1-deficient Macrophages.” J Biol Chem 292, no. 11 (March 17, 2017): 4651–62. https://doi.org/10.1074/jbc.M116.770735.

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Cohen, Sivan, Keiko Danzaki, and Nancie J. MacIver. “Nutritional effects on T-cell immunometabolism.” Eur J Immunol 47, no. 2 (February 2017): 225–35. https://doi.org/10.1002/eji.201646423.

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MacIver, Nancie J. “Oxytocin Treatment May Improve Infant Feeding and Social Skills in Prader-Willi Syndrome.” Pediatrics 139, no. 2 (February 2017). https://doi.org/10.1542/peds.2016-3833.

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Gerriets, Valerie A., Rigel J. Kishton, Marc O. Johnson, Sivan Cohen, Peter J. Siska, Amanda G. Nichols, Marc O. Warmoes, et al. “Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression.” Nat Immunol 17, no. 12 (December 2016): 1459–66. https://doi.org/10.1038/ni.3577.

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Siska, Peter J., Gerritje J. W. van der Windt, Rigel J. Kishton, Sivan Cohen, William Eisner, Nancie J. MacIver, Arnon P. Kater, J Brice Weinberg, and Jeffrey C. Rathmell. “Suppression of Glut1 and Glucose Metabolism by Decreased Akt/mTORC1 Signaling Drives T Cell Impairment in B Cell Leukemia.” J Immunol 197, no. 6 (September 15, 2016): 2532–40. https://doi.org/10.4049/jimmunol.1502464.

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Gerriets, Valerie A., Keiko Danzaki, Rigel J. Kishton, William Eisner, Amanda G. Nichols, Donte C. Saucillo, Mari L. Shinohara, and Nancie J. MacIver. “Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity.” Eur J Immunol 46, no. 8 (August 2016): 1970–83. https://doi.org/10.1002/eji.201545861.

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Petrovski, Slavé, Roberta E. Parrott, Joseph L. Roberts, Hongxiang Huang, Jialong Yang, Balachandra Gorentla, Talal Mousallem, et al. “Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature.” J Clin Immunol 36, no. 5 (July 2016): 462–71. https://doi.org/10.1007/s10875-016-0281-6.

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MacIver, Nancie J., Steven M. Thomas, Cynthia L. Green, and Gordon Worley. “Increased leptin levels correlate with thyroid autoantibodies in nonobese males.” Clin Endocrinol (Oxf) 85, no. 1 (July 2016): 116–21. https://doi.org/10.1111/cen.12963.

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Nagy, Eniko, Ramona M. Rodriguiz, William C. Wetsel, Nancie J. MacIver, and Laura P. Hale. “Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.” Plos One 11, no. 4 (2016): e0152764. https://doi.org/10.1371/journal.pone.0152764.

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Kountikov, Evgueni I., Jonathan C. Poe, Nancie J. Maclver, Jeffrey C. Rathmell, and Thomas F. Tedder. “A spontaneous deletion within the desmoglein 3 extracellular domain of mice results in hypomorphic protein expression, immunodeficiency, and a wasting disease phenotype.” Am J Pathol 185, no. 3 (March 2015): 617–30. https://doi.org/10.1016/j.ajpath.2014.10.025.

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