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Ivy E. Dick, PhD

Academic Title:

Associate Professor

Primary Appointment:

Physiology

Location:

Office: BRB 5031; 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.

Highlighted Publications

Bamgboye, M. A., Traficante, M. K., Owoyemi, J., DiSilvestre, D., Vieira, D. C. O. & Dick, I. E., Impaired Ca(V)1.2 inactivation reduces the efficacy of calcium channel blockers in the treatment of LQT8, J Mol Cell Cardiol. 2022 Dec; 173 92-100.

Bamgboye, M. A., Herold, K. G., Vieira, D. C. O., Traficante, M. K., Rogers, P. J., Ben-Johny, M. & Dick, I. E., CaV1.2 channelopathic mutations evoke diverse pathophysiological mechanisms, J Gen Physiol. 2022 Nov 7; 154(11): e202213209. Commentary.

Hussey, J. W., Limpitikul, W. B. & Dick, I. E., Calmodulin Mutations in Human Disease, Channels (Austin). 2023 Dec; 17(1): 2165278.

Sang, L., Vieira, D. C. O., Yue, D. T., Ben-Johny, M. & Dick, I. E., The molecular basis of the inhibition of CaV1 calcium-dependent inactivation by the distal carboxy tail, J Biol Chem. 2021 Jan-Jun; 296 100502.

 

Additional Publication Citations

Herold, K. G., Hussey, J. W. & Dick, I. E., CACNA1C-Related Channelopathies, Handb Exp Pharmacol. 2023 Jan 5; doi: 10.1007/164_2022_624.

Hussey, J. W., Herold, K. G. & Dick, I. E.  Voltage-gated calcium channelopathies. Calcium Signals: From Single Molecules to Physiology (eds Les Satin, Manu Ben Johny, & Ivy Dick) IOP. 2023; Vol. 4 Ch. 13,. 

Ben-Johny, M. & Dick, I. E. Calmodulin Regulation of Voltage-Gated Calcium ChannelsVoltage-Gated Calcium Channels  (ed G. W. Zamponi, Weiss, N. ) Springer, Cham., 2022; https://doi.org/10.1007/978-3-031-08881-0_9; 217-236. 

Chakouri, N., Rivas, S., Roybal, D., Yang, L., Diaz, J., Hsu, A., Mahling, R., Chen, B. X., Owoyemi, J. O., DiSilvestre, D., Sirabella, D., Corneo, B., Tomaselli, G. F., Dick, I. E., Marx, S. O. & Ben-Johny, M., Fibroblast growth factor homologous factors serve as a molecular rheostat in tuning arrhythmogenic cardiac late sodium current, Nat Cardiovasc Res. 2022 May; 1(5): 1-13.

Sang, L., Vieira, D. C. O., Yue, D. T., Ben-Johny, M. & Dick, I. E., The molecular basis of the inhibition of CaV1 calcium-dependent inactivation by the distal carboxy tail, J Biol Chem. 2021 Jan-Jun; 296 100502.

Brohus, M., Arsov, T., Wallace, D. A., Jensen, H. H., Nyegaard, M., Crotti, L., Adamski, M., Zhang, Y., Field, M. A., Athanasopoulos, V., Baro, I., Ribeiro de Oliveira-Mendes, B. B., Redon, R., Charpentier, F., Raju, H., DiSilvestre, D., Wei, J., Wang, R., Rafehi, H., Kaspi, A., Bahlo, M., Dick, I. E., Chen, S. R. W., Cook, M. C., Vinuesa, C. G., Overgaard, M. T. & Schwartz, P. J., Infanticide vs. inherited cardiac arrhythmias, 2021 Mar 8; 23(3): 441-450.

Niu, J. , Dick, I. E., Yang, W. , Bamgboye, M. A. , Yue, D. T., Tomaselli, G., Inoue, T. & Ben-Johny, M., Allosteric regulators selectively prevent Ca(2+)-feedback of CaV and NaV channels, 2018 Sep 10; 7 e35222.

Limpitikul, W. B., Greenstein, J. L., Yue, D. T., Dick, I. E. & Winslow, R. L., A bilobal model of Ca(2+)-dependent inactivation to probe the physiology of L-type Ca(2+) channels, J Gen Physiol. 2018 Dec 3; 150(12): 1688-1701.

Limpitikul, W. B. , Dick, I. E., Tester, D. J., Boczek, N. J., Limphong, P., Yang, W. , Choi, M. H., Babich, J. , DiSilvestre, D. , Kanter, R. J., Tomaselli, G. F., Ackerman, M. J. & Yue, D. T., A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long-QT Syndrome, Circ Res. 2017 Jan 06; 120(1): 39-48. Commentary

Niu, J., Ben Johny, M., Dick, I. E. & Inoue, T., Following Optogenetic Dimerizers and Quantitative Prospects, Biophys J. 2016 Aug 16; 6 1132-1140.

Sang, L. , Dick, I. E. & Yue, D. T., Protein kinase A modulation of CaV1.4 calcium channels, Nat Commun. 2016 July; 7 12239.

Limpitikul, W. B., Dick, I. E., Ben-Johny, M. & Yue, D. T., An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2+)-dependent regulation, Sci Rep. 2016 Jun; 6 27235.

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. & Tomaselli, G. F., A rendezvous with the queen of ion channels: Three decades of ion channel research by David T Yue and his Calcium Signals Laboratory, Channels (Austin). 2016 Jan/Feb; 10(1): 20-32. 

Dick, I. E., Joshi-Mukherjee, R., Yang, W. & Yue, D. T., Arrhythmogenesis in Timothy Syndrome is associated with defects in Ca(2+)-dependent inactivation, Nat Commun. 2016 Jan 29; 7

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.  

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

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

Dick, I. E., Tadross, M. R., Liang, H., Tay, L. H., Yang, W. & Yue, D. T., A modular switch for spatial Ca2+ selectivity in the calmodulin regulation of CaV channels, 2008 Feb 14; 451(7180): 830-834.

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) .  

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.

Research Interests

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.

Awards and Affiliations

 

2023 - Paul F. Cranefield Award: The Paul F. Cranefield Award was given to Ivy Dick by the Society of General Physiologists for the paper 'CaV1.2 channelopathic mutations evoke diverse pathophysiological mechanisms' published in the Journal of General Physiology. This work shows that differential effects on channel gating may underlie the cardiac vs. neurological phenotypes of Cav1.2 mutations. This is an important step to understand the pathogenesis of these mutations, and paves the way for future therapeutics

2016 - Appointed Assistant Professor in Physiology and named the inaugural John C. Hemmeter Scholar for 3 years.

In the News

Mutations in Calmodulin May Impact the Conviction of Kathleen Folbigg: In 2003 Kathleen Folbigg was convicted of murdering her four children, each of whom died of unknown causes before the age of two. However, new genetic evidence demonstrates that Folbigg and two of her children harbor a potentially pathogenic mutation within a gene encoding calmodulin, a ubiquitous calcium sensor which is critical in the normal function of the heart. Dr. Ivy Dick was part of an international research collaboration led by Drs. Schwartz, Overgaard and Vinuesa which demonstrated the potential pathogenetic effects of the mutation, leading to a new inquiry into the case.

Lab Techniques and Equipment

  • Electrophysiology: whole cell and single channel patch clamp
  • Molecular biology
  • Calcium and FRET imaging
  • Tissue culture and utilization of induced pluripotent stem cells (iPSCs)
  • CRISPR gene editing

Links of Interest