Richard Benninger, PhD

Professional Titles

• Professor of Bioengineering and Pediatrics
• Director Advanced Light Microscopy core

Research Interests

The Benninger lab is a multi-disciplinary team of scientists who are guided by engineering principles and technologies to study the endocrine pancreas (islets of Langerhans). With mechanistic knowledge underlying the dynamics of islet function and hormone release, we can develop diagnostics and therapeutic interventions to effectively manage, cure and prevent diabetes. Towards this goal the lab combines novel optical imaging and ultrasound imaging approaches to study the function of the islets of Langerhans over multiple levels of organization, and how function is disrupted in diabetes. Our research includes: 1) Systems biophysics of the islet of Langerhans in diabetes; 2) Electrical synapse (gap junction channel) plasticity; 3) Cell heterogeneity and emergent multicellular properties of the islet; 4) Advanced optical microscopy and ultrasound imaging; 5) Imaging diagnostics for type 1 diabetes.

Publications

• Kravets V, Benninger RKP. From the Transcriptome to Electrophysiology: Searching for the Underlying Cause of Diabetes. Cell Metab. 2020 May 5;31(5):888-889. PubMed PMID: 32375060
• Reusser TD, Song KH, Ramirez D, Benninger RK, Papadopoulou V, Borden MA. Phospholipid Oxygen Microbubbles for Image-Guided Therapy. Nanotheranostics. 2020;4(2):83-90. PubMed PMID: 32190535
• Bosma KJ, Syring KE, Oeser JK, Lee JD, Benninger RKP, Pamenter ME, O'Brien RM. Evidence that Evolution of the Diabetes Susceptibility Gene SLC30A8 that Encodes the Zinc Transporter ZnT8 Drives Variations in Pancreatic Islet Zinc Content in Multiple Species. J Mol Evol. 2019 Jul;87(4-6):147-151. PubMed PMID: 31273433
• Farnsworth NL, Walter R, Piscopio RA, Schleicher WE, Benninger RKP. Exendin-4 overcomes cytokine-induced decreases in gap junction coupling via protein kinase A and Epac2 in mouse and human islets. J Physiol. 2019 Jan;597(2):431-447. PubMed PMID: 30412665
• Dwulet JM, Ludin NWF, Piscopio RA, Schleicher WE, Moua O, Westacott MJ, Benninger RKP. How Heterogeneity in Glucokinase and Gap-Junction Coupling Determines the Islet [Ca(2+)] Response. Biophys J. 2019 Dec 3;117(11):2188-2203. PubMed PMID: 31753287
• Benninger RKP, Hodson DJ. New Understanding of ß-Cell Heterogeneity and In Situ Islet Function. Diabetes. 2018 Apr;67(4):537-547. PubMed PMID: 29559510
• Westacott MJ, Ludin NWF, Benninger RKP. Spatially Organized ß-Cell Subpopulations Control Electrical Dynamics across Islets of Langerhans. Biophys J. 2017 Sep 5;113(5):1093-1108. PubMed PMID: 28877492
• Westacott MJ, Farnsworth NL, St Clair JR, Poffenberger G, Heintz A, Ludin NW, Hart NJ, Powers AC, Benninger RKP. Age-Dependent Decline in the Coordinated [Ca(2+)] and Insulin Secretory Dynamics in Human Pancreatic Islets. Diabetes. 2017 Sep;66(9):2436-2445. PubMed PMID: 28588099
• Notary AM, Westacott MJ, Hraha TH, Pozzoli M, Benninger RK. Decreases in Gap Junction Coupling Recovers Ca2+ and Insulin Secretion in Neonatal Diabetes Mellitus, Dependent on Beta Cell Heterogeneity and Noise. PLoS Comput Biol. 2016 Sep;12(9):e1005116. PubMed PMID: 27681078
• Farnsworth NL, Walter RL, Hemmati A, Westacott MJ, Benninger RK. Low Level Pro-inflammatory Cytokines Decrease Connexin36 Gap Junction Coupling in Mouse and Human Islets through Nitric Oxide-mediated Protein Kinase Cd. J Biol Chem. 2016 Feb 12;291(7):3184-96. PubMed PMID: 26668311
• Nunemaker CS, Benninger RK. Zinc Transport Gets Its Zing Back: Double-Knockout of ZnT7 and ZnT8 Reveals the Importance of Zinc Transporters to Insulin Secretion. Endocrinology. 2016 Dec;157(12):4542-4544. PubMed PMID: 27911147
• Benninger RK. Fluorescence linear dichroism imaging for quantifying membrane order. Methods Mol Biol. 2015;1232:161-79. PubMed PMID: 25331136
• Hraha TH, Westacott MJ, Pozzoli M, Notary AM, McClatchey PM, Benninger RK. Phase transitions in the multi-cellular regulatory behavior of pancreatic islet excitability. PLoS Comput Biol. 2014 Sep;10(9):e1003819. PubMed PMID: 25188228
• Farnsworth NL, Hemmati A, Pozzoli M, Benninger RK. Fluorescence recovery after photobleaching reveals regulation and distribution of connexin36 gap junction coupling within mouse islets of Langerhans. J Physiol. 2014 Oct 15;592(20):4431-46. PubMed PMID: 25172942
• Hartney JM, Stidham T, Goldstrohm DA, Oberley-Deegan RE, Weaver MR, Valnickova-Hansen Z, Scavenius C, Benninger RK, Leahy KF, Johnson R, Gally F, Kosmider B, Zimmermann AK, Enghild JJ, Nozik-Grayck E, Bowler RP. A common polymorphism in extracellular superoxide dismutase affects cardiopulmonary disease risk by altering protein distribution. Circ Cardiovasc Genet. 2014 Oct;7(5):659-66. PubMed PMID: 25085920
• Nguyen LM, Pozzoli M, Hraha TH, Benninger RK. Decreasing cx36 gap junction coupling compensates for overactive KATP channels to restore insulin secretion and prevent hyperglycemia in a mouse model of neonatal diabetes. Diabetes. 2014 May;63(5):1685-97. PubMed PMID: 24458355
• Hang Y, Yamamoto T, Benninger RK, Brissova M, Guo M, Bush W, Piston DW, Powers AC, Magnuson M, Thurmond DC, Stein R. The MafA transcription factor becomes essential to islet ß-cells soon after birth. Diabetes. 2014 Jun;63(6):1994-2005. PubMed PMID: 24520122
• Hraha TH, Bernard AB, Nguyen LM, Anseth KS, Benninger RK. Dimensionality and size scaling of coordinated Ca(2+) dynamics in MIN6 ß-cell clusters. Biophys J. 2014 Jan 7;106(1):299-309. PubMed PMID: 24411262
• Benninger RK, Hutchens T, Head WS, McCaughey MJ, Zhang M, Le Marchand SJ, Satin LS, Piston DW. Intrinsic islet heterogeneity and gap junction coupling determine spatiotemporal Ca²? wave dynamics. Biophys J. 2014 Dec 2;107(11):2723-33. PubMed PMID: 25468351
• Nozik-Grayck E, Woods C, Taylor JM, Benninger RK, Johnson RD, Villegas LR, Stenmark KR, Harrison DG, Majka SM, Irwin D, Farrow KN. Selective depletion of vascular EC-SOD augments chronic hypoxic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2014 Dec 1;307(11):L868-76. PubMed PMID: 25326578
• Benninger RK, Piston DW. Cellular communication and heterogeneity in pancreatic islet insulin secretion dynamics. Trends Endocrinol Metab. 2014 Aug;25(8):399-406. PubMed PMID: 24679927
• Farnsworth NL, Benninger RK. New insights into the role of connexins in pancreatic islet function and diabetes. FEBS Lett. 2014 Apr 17;588(8):1278-87. PubMed PMID: 24583073
• Benninger RK, Piston DW. Two-photon excitation microscopy for the study of living cells and tissues. Curr Protoc Cell Biol. 2013 Jun;Chapter 4:Unit 4.11.1-24. PubMed PMID: 23728746
• Head WS, Orseth ML, Nunemaker CS, Satin LS, Piston DW, Benninger RK. Connexin-36 gap junctions regulate in vivo first- and second-phase insulin secretion dynamics and glucose tolerance in the conscious mouse. Diabetes. 2012 Jul;61(7):1700-7. PubMed PMID: 22511206

Professional Memberships

• American Diabetes Association, professional member
• Biophysical Society, member