Iowa City, IA 52242
Graduate School: Biomolecular Chemistry, University of Wisconsin-Madison
Post-doctoral Fellowship: Pharmacology, University of Iowa
Ca2+ is critical for modulating numerous cellular processes in excitable cells such as action potential duration, myocyte contraction, secretion, energy production, and gene expression. We are interested in how excitable cells such as cardiomyocytes modulate intracellular Ca2+ concentration and to what degree individual levels of control affect cellular and in vivo function. We hypothesize that dynamic Ca2+ regulation is critical for normal cellular function and that mechanisms that interfere with this process underlie pathological disease. Specifically, we are focused on how Ca2+ enters cells through L-type Ca2+ channels and how intracellular Ca2+ is sensed and integrated by mitochondria to adapt to changing energy demands. The CaV1.2 L-type calcium channel is the major route of Ca2+ influx in the heart and brain. CaV1.2 is both positively and negatively regulated by Ca2+ in addition to kinases, phosphatases, and the cytoskeleton. Dr. Hall has long been interested in how individual subunits and regulators within the CaV1.2 macromolecular signaling complex assemble to regulate channel function. More recently, we have expanded our research interests to determine how mitochondrial function integrates and shapes cellular responses. We are taking novel genetic approaches to target L-type Ca2+ channels and mitochondrial components with the goal of examining their functional relevance in vivo.
- 1: Xu H, Ginsburg KS, Hall DD, Zimmermann M, Stein IS, Zhang M, Tandan S, HillJA, Horne MC, Bers D, Hell JW. Targeting of protein phosphatases PP2A and PP2B tothe C-terminus of the L-type calcium channel Ca v1.2. Biochemistry. 2010 Dec7;49(48):10298-307. doi: 10.1021/bi101018c. Epub 2010 Nov 11. PubMed PMID:21053940; PubMed Central PMCID: PMC3075818.
- Gao Z, Singh MV, Hall DD, Koval OM, Luczak ED, Joiner ML, Chen B, Wu Y, Chaudhary AK, Martins JB, Hund TJ, Mohler PJ, Song LS, Anderson ME. Catecholamine-independent heart rate increases require Ca2+/calmodulin-dependent protein kinase II. Circ Arrhythm Electrophysiol. 2011 Jun 1;4(3):379-87. Epub 2011 Mar 15. PubMed PMID: 21406683; PubMed Central PMCID: PMC3116039.
- Joiner ML, Koval OM, Li J, He BJ, Allamargot C, Gao Z, Luczak ED, Hall DD, Fink BD, Chen B, Yang J, Moore SA, Scholz TD, Strack S, Mohler PJ, Sivitz WI, Song LS, Anderson ME. CaMKII determines mitochondrial stress responses in heart. Nature. 2012 Nov 8;491(7423):269-73. doi: 10.1038/nature11444. Epub 2012 Oct 10. PubMed PMID: 23051746; PubMed Central PMCID: PMC3471377.interaction between calcineurin and the cardiac L-type Ca2+ channel. Circ. Res., in press.
- Gao Z, Rasmussen TP, Li Y, Kutschke W, Koval OM, Wu Y, Wu Y, Hall DD, Joiner ML, Wu X, Dominic Swaminathan P, Purohit A, Zimmerman KA, Weiss RM, Philipson K, Song LS, Hund TJ, Anderson ME. Genetic Inhibition of Na+-Ca2+ Exchanger Current Disables Fight or Flight Sinoatrial Node Activity Without Affecting Resting Heart Rate. Circ Res. 2012 Nov 27. PubMed PMID: 23192947