Craig S. Nunemaker, PhD
Graduate School: PhD - Neuroscience, University of Virginia
Postdoctoral Fellowship, Physiology/Diabetes - Virginia Commonwealth University
Primary Appointment: Associate Professor, Medicine and Pharmacology; Director, Pancreatic Cell and Islet Isolation Core, UVA Diabetes Center
Diabetes, mechanisms of beta-cell dysfunction, calcium signaling, low-grade systemic inflammation.
Email Address: email@example.com
Dr. Nunemaker's lab seeks to understand 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. Dr. Nunemaker's Lab is chiefly interested in low-grade systemic inflammation as a possible trigger of beta-cell decline.
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. Dr. Nunemaker's work has shown that pro-inflammatory cytokines at these circulating levels are sufficient to interfere with 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.
Current work focuses on possible sources 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, Dr. Nunemaker's Lab hopes to identify early and reversible steps in beta-cell decline in order to prevent the development of T2D.
Geisler JC, Corbin KL, Li Q, Feranchak AP, Nunemaker CS, Li C.
Vesicular nucleotide transporter-mediated ATP release regulates insulin
secretion. Endocrinology. 2013 Feb;154(2):675-84. doi:
10.1210/en.2012-1818. Epub 2012 Dec 19. PubMed PMID: 23254199; PubMed
Central PMCID: PMC3548185.
Wang F, Kohan AB, Kindel TL, Corbin KL, Nunemaker CS, Obici S, Woods SC, Davidson WS, Tso P. Apolipoprotein A-IV improves glucose homeostasis by enhancing insulin secretion. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9641-6. doi: 10.1073/pnas.1201433109. Epub 2012 May 22. PubMed PMID: 22619326; PubMed Central PMCID: PMC3386109.
Ramadan JW, Steiner SR, O'Neill CM, Nunemaker CS. The central role of calcium in the effects of cytokines on beta-cell function: implications for type 1 and type 2 diabetes. Cell Calcium. 2011 Dec;50(6):481-90. doi: 10.1016/j.ceca.2011.08.005. Epub 2011 Sep 23. Review. PubMed PMID: 21944825; PubMed Central PMCID: PMC3223281.
Corbin KL, Hall TE, Haile R, Nunemaker CS. A novel fluorescence imaging approach for comparative measurements of pancreatic islet function in vitro. Islets. 2011 Jan-Feb;3(1):14-20. Epub 2011 Jan 1. PubMed PMID: 21266850; PubMed Central PMCID: PMC3060435.
Dula SB, Jecmenica M, Wu R, Jahanshahi P, Verrilli GM, Carter JD, Brayman KL, Nunemaker CS. Evidence that low-grade systemic inflammation can induce islet dysfunction as measured by impaired calcium handling. Cell Calcium. 2010
Aug-Sep;48(2-3):133-42. doi: 10.1016/j.ceca.2010.07.007. Epub 2010 Aug 25. PubMed PMID: 20800281; PubMed Central PMCID: PMC2948622.
Crim WS, Wu R, Carter JD, Cole BK, Trace AP, Mirmira RG, Kunsch C, Nadler JL, Nunemaker CS. AGI-1067, a novel antioxidant and anti-inflammatory agent, enhances insulin release and protects mouse islets. Mol Cell Endocrinol. 2010 Jul 29;323(2):246-55. doi: 10.1016/j.mce.2010.02.041. Epub 2010 Mar 6. PubMed PMID: 20211684; PubMed Central PMCID: PMC2875300.
Cole BK, Keller SR, Wu R, Carter JD, Nadler JL, Nunemaker CS. Valsartan protects pancreatic islets and adipose tissue from the inflammatory and metabolic consequences of a high-fat diet in mice. Hypertension. 2010 Mar;55(3):715-21. doi: 10.1161/HYPERTENSIONAHA.109.148049. Epub 2010 Jan 25. PMID: 20100990. PubMed Central PMCID: PMC2836256.
Nunemaker CS, Dishinger JF, Dula SB, Wu R, Merrins MJ, Reid KR, Sherman A, Kennedy RT, Satin LS. Glucose metabolism, islet architecture, and genetic homogeneity in imprinting of [Ca2+](i) and insulin rhythms in mouse islets. PLoS One. 2009 Dec 23;4(12):e8428. doi: 10.1371/journal.pone.0008428. PMID: 20037650; PubMed Central PMCID: PMC2793028.
Carter JD, Dula SB, Corbin KL, Wu R, Nunemaker CS. A practical guide to rodent islet isolation and assessment. Biol Proced Online. 2009 Dec 3;11:3-31. doi: 10.1007/s12575-009-9021-0.
PMID: 19957062; PubMed Central PMCID: PMC3056052
Evidence of diminished glucose stimulation and endoplasmic reticulum function in nonoscillatory pancreatic islets. Jahanshahi P, Wu R, Carter JD, Nunemaker CS. Endocrinology. 2009 Feb;150(2):607-15. doi: 10.1210/en.2008-0773. Epub 2008 Sep 25. PMID: 18818288; PubMed Central PMCID: PMC2646533.
|Office Address:||PO Box 801413
Charlottesville, VA 22908-1413