Physicians

Department / Division
Pediatrics / Pediatrics-Endocrinology

Address
DUMC 102820
Durham, NC 27710

Appointment Telephone
919-684-3772, option 2

Office Telephone
919-684-8292

Fax Telephone
919-684-8613

Training

• MD, Mayo Medical School (Minnesota), 2003

Residency

• Pediatrics, Duke University Medical Center, 2003-2006

Fellowship

• Pediatric Endocrinology, Duke University Medical Center, 2006-2009

Other Training

• PhD, Immunology, Mayo Graduate School (Minnesota), 2003

Clinical Interests
Short stature, puberty, polycystic ovarian syndrome, thyroid disease

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.

Industry Relationships and Collaborations (What's this?)

This physician has no reported relationships with industry.

Representative Publications
Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 2011 Mar 15;186(6):3299-303. (2011) Abstract

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. (2008) Abstract

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. (2008) Abstract