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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) 684-3772
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

Gerriets, Valerie A., and Nancie J. MacIver. “Role of T cells in malnutrition and obesity.” Front Immunol 5 (2014): 379. https://doi.org/10.3389/fimmu.2014.00379.

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MacIver, Nancie J., Ryan D. Michalek, and Jeffrey C. Rathmell. “Metabolic regulation of T lymphocytes.” Annu Rev Immunol 31 (2013): 259–83. https://doi.org/10.1146/annurev-immunol-032712-095956.

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MacIver, Nancie J., Julianna Blagih, Donte C. Saucillo, Luciana Tonelli, Takla Griss, Jeffrey C. Rathmell, and Russell G. Jones. “The liver kinase B1 is a central regulator of T cell development, activation, and metabolism.” J Immunol 187, no. 8 (October 15, 2011): 4187–98. https://doi.org/10.4049/jimmunol.1100367.

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Michalek, Ryan D., Valerie A. Gerriets, Sarah R. Jacobs, Andrew N. Macintyre, Nancie J. MacIver, Emily F. Mason, Sarah A. Sullivan, Amanda G. Nichols, and Jeffrey C. Rathmell. “Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.” J Immunol 186, no. 6 (March 15, 2011): 3299–3303. https://doi.org/10.4049/jimmunol.1003613.

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Maciver, Nancie J., Sarah R. Jacobs, Heather L. Wieman, Jessica A. Wofford, Jonathan L. Coloff, and Jeffrey C. Rathmell. “Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival.” J Leukoc Biol 84, no. 4 (October 2008): 949–57. https://doi.org/10.1189/jlb.0108024.

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Jacobs, Sarah R., Catherine E. Herman, Nancie J. Maciver, Jessica A. Wofford, Heather L. Wieman, Jeremy J. Hammen, and Jeffrey C. Rathmell. “Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways.” J Immunol 180, no. 7 (April 1, 2008): 4476–86. https://doi.org/10.4049/jimmunol.180.7.4476.

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Solan, Nancie J., Hiroko Miyoshi, Eva M. Carmona, Gary D. Bren, and Carlos V. Paya. “RelB cellular regulation and transcriptional activity are regulated by p100.” J Biol Chem 277, no. 2 (January 11, 2002): 1405–18. https://doi.org/10.1074/jbc.M109619200.

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Carmona, Eva M., Nancie J. Solan, Gary D. Bren, and Carlos V. Paya. “p100 is the main inhibitor of RelB, the major component of NF-κB in differentiated macrophages.” In Journal of Allergy and Clinical Immunology, 109:S323–S323. Elsevier BV, 2002. https://doi.org/10.1016/s0091-6749(02)82135-2.

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Asin, S., G. D. Bren, E. M. Carmona, N. J. Solan, and C. V. Paya. “NF-kappaB cis-acting motifs of the human immunodeficiency virus (HIV) long terminal repeat regulate HIV transcription in human macrophages.” J Virol 75, no. 23 (December 2001): 11408–16. https://doi.org/10.1128/JVI.75.23.11408-11416.2001.

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Bren, G. D., N. J. Solan, H. Miyoshi, K. N. Pennington, L. J. Pobst, and C. V. Paya. “Transcription of the RelB gene is regulated by NF-kappaB.” Oncogene 20, no. 53 (November 22, 2001): 7722–33. https://doi.org/10.1038/sj.onc.1204868.

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