Nancie J. MacIver, MD, PhD

Medical Instructor in the Department of Pediatrics

Department:
Pediatrics

Division:
Endocrinology

Mailing Address:
DUMC 3080 Durham, NC 27710

Appointment Telephone:
919-684-3772, option 2

Office Telephone:
919-684-8292

Fax:
919-684-8613

Training:
MD, Mayo Medical School (Minnesota), 2003

Fellowship:
Pediatric Endocrinology, Duke University Medical Center, 2006-2009

Residency:
Pediatrics, Duke University Medical Center, 2003-2006

Clinical Interests:
Caring for children with disorders of growth, development, or hormonal regulation such as adrenal, thyroid, pituitary, pubertal, growth or metabolic disorders

Research Interests:
My research investigates the role of the hormone leptin in immune cell function.  Leptin is secreted by adipocytes and is well known for its effects on appetite and weight regulation.  Deficits in adipose tissue, as seen in malnutrition, lead to a deficiency of leptin, which plays a critical role in metabolic regulation as well as the development of immune function.  Leptin-deficient individuals have a decrease in both total T and CD4 T cell number along with abnormal T cell function, making them more susceptible to intracellular infections and atopic disease, while administration of recombinant leptin protein reverses both the metabolic defects and immune abnormalities.  

The mechanisms by which leptin regulates lymphocyte number and function are not completely understood.  Preliminary data suggest that leptin's effects on T cell function require activation of the T cell by signaling at both the T cell receptor (TCR) and co-stimulatory membrane protein CD28; that leptin activates the metabolic mediator AMP-activated protein kinase (AMPK) in lymphocytes; and that leptin is necessary for glucose uptake in activated cells.  For these reasons, we hypothesize that the effects of leptin on lymphocyte number and function require full T cell stimulation and are mediated in part by leptin's effects on cellular metabolism.

Publications:
MacIver NJ, Jacobs SR, Wieman HL, Wofford JA, Coloff JL, Rathmell JC. Glucose metabolism in lymphocytes is a regulated process with significant effects on immune cell function and survival.  J Leukoc Biol.  2008 Oct;84(4):949-57.

Jacobs SR, Herman CE, MacIver NJ, Wofford JA, Wieman HL, Hammen JJ, Rathmell JC. Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways.  J Immunol.  2008 Apr 1;180(7):4476-86.