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Nancie Jo MacIver

Adjunct Associate Professor in the Department of Pediatrics
Pediatrics, Endocrinology
DUMC Box 102820, Durham, NC 27710
3000 Erwin Road, Suite 200, Durham, NC 27710

Overview


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. 

Current Appointments & Affiliations


Adjunct Associate Professor in the Department of Pediatrics · 2021 - Present Pediatrics, Endocrinology, Pediatrics
Assistant Professor in Immunology · 2015 - Present Integrative Immunobiology, Basic Science Departments
Assistant Professor in Pharmacology and Cancer Biology · 2016 - Present Pharmacology & Cancer Biology, Basic Science Departments
Member of Duke Molecular Physiology Institute · 2013 - Present Duke Molecular Physiology Institute, Duke Molecular Physiology Institute

Education, Training & Certifications


Mayo School of Health Sciences · 2003 M.D.
Mayo School of Health Sciences · 2003 Ph.D.