Craig S. Nunemaker, Ph.D.

Craig S. Nunemaker, Ph.D.

  • Associate Professor, Departments of Medicine (Division of Endocrinology and Metabolism) and Pharmacology
  • Director, Pancreatic Cell and Islet Isolation Core (UVA Diabetes Center)


  • Undergraduate: B.S., College of William and Mary, Williamsburg, VA (Physics)
  • Graduate: Ph.D., University of Virginia, Charlottesville, VA (Neuroscience)
  • Postdoctoral training: Virginia Commonwealth University, Richmond, VA (Physiology/Diabetes) 


Research Interests: Diabetes, mechanisms of beta-cell dysfunction, calcium signaling, low-grade systemic inflammation

Research Description:  The long-term goal of my research is to determine the mechanisms of inflammatory-mediated beta-cell dysfunction that occurs in diabetes and other metabolic disorders. Obesity is strongly associated with the development of type 2 diabetes (T2D), yet obesity leads to T2D for only a minority of individuals. A key factor in the development of T2D is the decline of insulin-producing pancreatic beta-cells. Among the obesity-associated triggers of beta-cell decline, low-grade systemic inflammation is perhaps one of the earliest to occur. The added metabolic stress of obesity, particularly on adipose tissue, induces the secretion of cytokines, which leads to a state of low-grade systemic inflammation consisting of a modest increase in circulating cytokine levels. We have shown that pro-inflammatory cytokines at these circulating levels are sufficient to disrupt intracellular calcium handling in normal beta-cells without substantially disrupting insulin secretion or causing cell death.

Beta-cells from diabetes-prone mice, however, show much greater susceptibility to cytokine-mediated dysfunction and increased rates of calcium-mediated cell death, even prior to the first symptoms of diabetes. We are actively investigating possible source(s) of dysfunctional calcium handling including endoplasmic reticulum stress, mitochondrial disruption, and ion-channel dysfunction using a combination of physiological and molecular approaches. By identifying the physiological impact of cytokines at very low doses, we hope to identify early and reversible steps in beta-cell decline in order to prevent the development of T2D.

We are also developing techniques to assess and improve beta-cell health and function. One project involves a novel calcium imaging technique that controls for differences in background fluorescence, temperature, and perifusion dynamics in order to improve our sensitivity in detecting beta-cell dysfunction (see Corbin et al., Islets 3(1):14-20, 2011). A related project involves subcellular mapping of calcium movement within the beta-cell during glucose stimulation using laser-scanning confocal microscopy to characterize calcium flux within the nucleus, endoplasmic reticulum, and mitochondria. These techniques will be used to identify primary source(s) of beta-cell dysfunction and to assess potential diabetes treatments at the beta-cell level.

Our research is supported by: 

  • NIH R01 DK089182 (NIDDK, PI Nunemaker, “Low-grade inflammation, cytokines, and beta-cell dysfunction in type 2 diabetes,” 07/29/11-05/31/16)