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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

Kiernan, Kaitlin, and Nancie J. MacIver. “A Novel Mechanism for Th17 Inflammation in Human Type 2 Diabetes Mellitus..” Trends Endocrinol Metab, November 22, 2019. https://doi.org/10.1016/j.tem.2019.11.002.

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Rebeles, Jennifer, William D. Green, Yazan Alwarawrah, Amanda G. Nichols, William Eisner, Keiko Danzaki, Nancie J. MacIver, and Melinda A. Beck. “Obesity-Induced Changes in T-Cell Metabolism Are Associated With Impaired Memory T-Cell Response to Influenza and Are Not Reversed With Weight Loss..” J Infect Dis 219, no. 10 (April 19, 2019): 1652–61. https://doi.org/10.1093/infdis/jiy700.

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Kiernan, Kaitlin, and Nancie J. MacIver. “Viral Infection "Interferes" with Glucose Tolerance..” Immunity 49, no. 1 (July 17, 2018): 6–8. https://doi.org/10.1016/j.immuni.2018.06.013.

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Alwarawrah, Yazan, Kaitlin Kiernan, and Nancie J. MacIver. “Changes in Nutritional Status Impact Immune Cell Metabolism and Function..” Front Immunol 9 (2018). https://doi.org/10.3389/fimmu.2018.01055.

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Alwarawrah, Y., and N. J. MacIver. “Immune function in obesity.” In Contemporary Endocrinology, 363–78, 2018. https://doi.org/10.1007/978-3-319-68192-4_22.

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Huang, Ying, Yiqun Jiao, Peijie Shi, Xiaoli Nie, Wei Huang, Michael Choi, Andrew N. Macintyre, et al. “Role of Glucose Transporter 1 in Graft-Versus-Host Disease and Graft-Versus-Tumor Effect.” In Blood, Vol. 130. AMER SOC HEMATOLOGY, 2017.

Scholars@Duke

MacIver, Nancie J., and Jeffrey C. Rathmell. “Editorial overview: Metabolism of T cells: integrating nutrients, signals, and cell fate..” Curr Opin Immunol 46 (June 2017): viii–xi. https://doi.org/10.1016/j.coi.2017.06.002.

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Green, William David, Jennifer Rebeles, Terry J. Noah, Michael G. Hudgens, Sam S. Weir, Nancie J. MacIver, and Melinda A. Beck. “Altered Metabolism and Function of T Cells Isolated from Influenza Vaccinated Obese Adults.” In Faseb Journal, Vol. 31. FEDERATION AMER SOC EXP BIOL, 2017.

Scholars@Duke

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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