HH Room 511A, Lab - HH Room 511B
Education and Training
I began my studies of ion channels as an electrophysiologist at Merck in the laboratories of Dr. Charles Cohen and Dr. Owen McManus where I characterized the pharmacological modulation of voltage gated sodium channels. In 2004, I joined the Calcium Signals Lab at Johns Hopkins as a graduate student under the direction of Dr. David Yue. My research focused on understanding the spatial selectivity of calmodulin regulation of voltage gated calcium channels. Upon graduation, I elected to remain in the Calcium Signals lab for my post-doctoral research and later as a Research Associate, and continued my research on the mechanisms underlying calmodulin regulation of calcium channels, and how those mechanisms are disrupted in Timothy Syndrome.
Limpitikul W. B., Dick I. E., Tester D. J., BoczekN. J., Limphong P., Yang W., Choi M.H., Babich J., DiSilvestre D., Kanter R. J., Tomaselli G. F., Ackerman M.J., and Yue D. T. (2017) A precision medicine approach to the rescue of function in malignant calmodulinopathic long QT syndrome. Circulation Research 2017 Jan 6;120(1):39-48. Epub 2016 Oct 20. PMCID: PMC5516949
Niu J., Johny M.B., Dick I.E., Inoue T. (2016) Following optogenetic dimerizers and quantitiative prospects. Biophysical Journal 2016 Sep 20;111(6):1132-40. PMCID: PMC5034304
Sang L, Dick I. E.*, and Yue D. T. (2016) Protein Kinase A modulation of L-type calcium channels. Nature Communications 7, 12239. *corresponding author PMCID: PMC4963476
Dick I. E.*, Joshi-Mukherjee R, Yang W, and Yue D. T. (2016) Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca2+ dependent inactivation. Nature Communications 7, 10370. *corresponding author PMCID: PMC4740114
Adams, P. J., Ben-Johny, M., Dick, I. E., Inoue, T., and Yue, D. T. (2014) Apocalmodulin itself promotes ion channel opening and Ca2+ regulation, Cell 159, 608-622. PMCID: PMC4349394
Dick, I. E., Tadross, M. R., Liang, H., Tay, L. H., Yang, W., and Yue, D. T. (2008) A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels, Nature 451, 830-834. (Faculty of 1000: Biology: http://f1000biology.com/article/id/1102182/evaluation). PMCID: PMC4262256
Limpitikul W. B., Dick, I. E., Ben-Johny M., and Yue D. T. (2016) An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca2+- dependent regulation. Scientific Reports 6, 27235. *corresponding author. PMCID: PMC4891671
Bazzazi H, Sang L, Dick I. E., Joshi-Mukherjee R, Yang W, and Yue D. T. (2015) Novel fluorescence resonance energy transfer-based reporter reveals differential calcineurin activation in neonatal and adult cardiomyocytes. The Journal of physiology 593:3865-3884. PMCID: PMC4575574
Dick I. E., Limpitikul W. B., Niu J, Banerjee R, Issa J. B., Ben-Johny M, Adams P. J., Kang P. W., Lee S. R., Sang L, Yang W, Babich J, Zhang M, Bazazzi H, Yue N. C., and Tomaselli G. F. (2015) A rendezvous with the queen of ion channels: Three decades of ion channel research by david t. Yue and his calcium signals laboratory. Channels 10(1):20-32. PMCID: PMC4802785
Ben-Johny M., Dick I. E., Sang L., Limpitikul W. B., Kang P. W., Niu J., Banerjee R., Yang W., Babich J.S., Issa J. B., Lee S. R., Namkung H., Li J., Zhang M., Yang P. S., Bazzazi H., Adams P. J., Joshi-Mukherjee R., Yue D. N., and Yue D. T. (2015) Towards a unified theory of calmodulin regulation (calmodulation) of voltage-gated calcium and sodium channels. Current molecular pharmacology 8(2):188-205. PMCID: PMC4960983
Limpitikul, W. B., Dick, I. E., Joshi-Mukherjee, R., Overgaard, M. T., George, A. L., Jr., and Yue, D. T. (2014) Calmodulin mutations associated with long QT syndrome prevent inactivation of cardiac L-type Ca currents and promote proarrhythmic behavior in ventricular myocytes, Journal of molecular and cellular cardiology 74C, 115-124. PMCID: PMC4262253
Joshi-Mukherjee, R., Dick, I. E., Liu, T., O'Rourke, B., Yue, D. T., and Tung, L. (2013) Structural and functional plasticity in long-term cultures of adult ventricular myocytes, Journal of molecular and cellular cardiology 65, 76-87. PMCID: PMC4219275
Tay, L. H., Dick, I. E., Yang, W., Mank, M., Griesbeck, O., and Yue, D. T. (2012) Nanodomain Ca2+ of Ca2+ channels detected by a tethered genetically encoded Ca2+ sensor, Nature communications 3, 778. PMCID: PMC3615648
Tadross, M. R., Dick, I. E., and Yue, D. T. (2008) Mechanism of local and global Ca2+ sensing by calmodulin in complex with a Ca2+ channel, Cell 133, 1228-1240. (Cover Article) (Faculty of 1000: Biology: http://f1000biology.com/article/id/1119808/evaluation).
Dick, I. E., Brochu, R. M., Purohit, Y., Kaczorowski, G. J., Martin, W. J., and Priest, B. T. (2007) Sodium channel blockade may contribute to the analgesic efficacy of antidepressants, J Pain 8, 315-324.
Liu, C. J., Priest, B. T., Bugianesi, R. M., Dulski, P. M., Felix, J. P., Dick, I. E., Brochu, R. M., Knaus, H. G., Middleton, R. E., Kaczorowski, G. J., Slaughter, R. S., Garcia, M. L., and Kohler, M. G. (2006) A high-capacity membrane potential FRET-based assay for NaV1.8 channels, Assay Drug Dev Technol 4, 37-48.
Brochu, R. M., Dick, I. E., Tarpley, J. W., McGowan, E., Gunner, D., Herrington, J., Shao, P. P., Ok, D., Li, C., Parsons, W. H., Stump, G. L., Regan, C. P., Lynch, J. J., Jr., Lyons, K. A., McManus, O. B., Clark, S., Ali, Z., Kaczorowski, G. J., Martin, W. J., and Priest, B. T. (2006) Block of peripheral nerve sodium channels selectively inhibits features of neuropathic pain in rats, Mol Pharmacol 69, 823-832.
Liang, J., Brochu, R. M., Cohen, C. J., Dick, I. E., Felix, J. P., Fisher, M. H., Garcia, M. L., Kaczorowski, G. J., Lyons, K. A., Meinke, P. T., Priest, B. T., Schmalhofer, W. A., Smith, M. M., Tarpley, J. W., Williams, B. S., Martin, W. J., and Parsons, W. H. (2005) Discovery of potent and use-dependent sodium channel blockers for treatment of chronic pain, Bioorg Med Chem Lett 15, 2943-2947.
Herrington, J., Sanchez, M., Wunderler, D., Yan, L., Bugianesi, R. M., Dick, I. E., Clark, S. A., Brochu, R. M., Priest, B. T., Kohler, M. G., and McManus, O. B. (2005) Biophysical and pharmacological properties of the voltage-gated potassium current of human pancreatic beta-cells, J Physiol 567, 159-175.
Priest, B. T., Garcia, M. L., Middleton, R. E., Brochu, R. M., Clark, S., Dai, G., Dick, I. E., Felix, J. P., Liu, C. J., Reiseter, B. S., Schmalhofer, W. A., Shao, P. P., Tang, Y. S., Chou, M. Z., Kohler, M. G., Smith, M. M., Warren, V. A., Williams, B. S., Cohen, C. J., Martin, W. J., Meinke, P. T., Parsons, W. H., Wafford, K. A., and Kaczorowski, G. J. (2004) A disubstituted succinamide is a potent sodium channel blocker with efficacy in a rat pain model, Biochemistry 43, 9866-9876.
Felix, J. P., Williams, B. S., Priest, B. T., Brochu, R. M., Dick, I. E., Warren, V. A., Yan, L., Slaughter, R. S., Kaczorowski, G. J., Smith, M. M., and Garcia, M. L. (2004) Functional assay of voltage-gated sodium channels using membrane potential-sensitive dyes, Assay Drug Dev Technol 2, 260-268.
Smith, H. A., Church, J., Fournier, J., Lisle, J., Gay, P., Kolenberg, K., Carney, B. W., Dick, I., Peterson, R., and Hakes, B. (2003) The Blazhko Effect of RR Lyrae in 1996, Publ. Astron. Soc. Pacific 115, 43-48.
Voltage-gated calcium channels (CaV) are critical conduits for Ca2+ entry into the heart, smooth muscle and brain. Ca2+ entry through these channels must be precisely controlled, thus these channels employ two major forms of feedback regulation: voltage dependent inactivation (VDI) and Ca2+ dependent inactivation (CDI). Disruption of these important regulatory processes results in severe clinical phenotypes including autism, ataxia and long QT syndrome. My research has focused on gaining mechanistic understanding of these regulatory processes, and applying those findings to gain new insight into the pathogenesis and treatment options for Ca2+ channelopathies and related diseases. Recent work has focused on unraveling the mechanisms leading to cardiac arrhythmias in calcium channelopathies such as Timothy Syndrome (TS). By examining the inactivation defects underlying two different L-type channel TS mutations, we uncovered a remarkable divergence in the mechanisms leading to deficits in CDI. These findings promise new insight into customized treatment for TS, and illustrate how in depth biophysical understanding can inform on therapeutic interventions in patients. Overall, my lab studies the mechanisms underlying the regulation of voltage-gated calcium channels, how these mechanisms are disrupted by genetic mutations, and how new therapeutic strategies can address these disruptions.
2016 - Appointed Assistant Professor in Physiology and named the inaugural John C. Hemmeter Scholar for 3 years.
2017 - Maryland Stem Cell Research Fund Discovery award
- Electrophysiology: whole cell and single channel patch clamp
- Molecular biology
- Calcium and FRET imaging
- Tissue culture and utilization of induced pluripotent stem cells (iPSCs)