Carl J. Shapiro Science Center, 322B
DegreesHarvard University, M.D.
Harvard University, Ph.D.
Brandeis University, M.A.
Brandeis University, B.A.
ExpertiseIon channels, and how they operate in health and illness
Our research is directed towards understanding how ion channels operate in health and illness. These integral membrane proteins catalyze the selective transfer of ions across membranes and, like enzymes, show exquisite specificity and tight regulation. As a class, ion channels orchestrate the electrical activity that allows operation of the heart, nervous system and skeletal muscles--even the signals in T cells require ion channels. Less sensational but equally important, ion channels mediate cellular fluid and electrolyte homeostasis. Remarkably, fundamental questions remain to be answered. How do ion channels open and close? What is their architecture? How do mutations produce cardiac arrhythmia, hypertension, seizures, or deafness? How do drugs act to produce beneficial outcomes (~20% of our current pharmacopeia targets ion channels) or to yield undesirable side effects? Our laboratory uses macroscopic and single molecule electrophysiology and spectroscopy, molecular genetics, high-throughput and structural methods to pursue five research directions. Webpage
|BCBP||255a||Ion Channels in Human Disease|
|BCBP||297a||Master's Lab Research I|
|BCBP||297b||Master's Lab Research II|
Awards and Honors
Fellow, American Academy of Pediatrics (2008)
Editor-in-Chief, Quarterly Reviews of Biophysics (2002 - 2007)
E. Mead Johnson Award (Society for Pediatric Research) (2001)
Ruscic, K.J., Miceli, F., Villalba-Galea, C.A., Dai, H., Mishina, Y., Bezanilla, F. and Goldstein, Steve A. N.. "IKs channels open slowly because KCNE1 accessory subunits slow the movement of S4 voltage sensors in KCNQ1 pore-forming subunits.." Proc. Natl. Acad. Sci 10. 1073 (2013): Early Edition published ahead of print.
Silva, J.R. and Goldstein, Steve A. N.. "Voltage Sensor Movements Describe Slow Inactivation of Voltage-gated Sodium Channels II: a Periodic Paralysis Mutation in NaV1.4 (L689I).." Journal of General Physiology 141. 3 (2013): 323-334.
Plant, L.D., Zuniga, L., Araki, D., Marks, J.D. and Goldstein, Steve A. N.. "SUMOylation silences heterodimeric TASK potassium channels containing K2P1 subunits in cerebellar granule neurons.." Science Signaling 5. 251 (2012): 84.
Plant, L.D., Dowdell, E.J., Dementieva, I.S., Marks, J.D. and Goldstein, Steve A. N.. "SUMO modification of cell surface Kv2.1 potassium channels regulates the activity of rat hippocampal neurons.." J. Gen. Physiol. 137. 1 (2011): 441-54.
Takacs, Z., Toups, M., Kollewe, A., Johnson, E., Cuello, L.G., Driessens, G., Biancalana, M., Koide, A., Ponte, C.G., Perozo, E., Gajewski, T.F., Suarez-Kurtz, G., Koide, S., and Goldstein, Steve A. N.. "A designer ligand specific for Kv1.3 channels from a scorpion neurotoxin-based library.." Proc. Natl Acad Sci 106. 1 (2009): 22211-6.
Thomas, D., Plant, L.D., Wilkens, C.M., McCrossan, Z.A. and Goldstein, Steve A. N.. "Alternative translation initiation in rat brain yields K2P2.1 potassium channels permeable to sodium." Neuron 58. 1 (2008): 859-870.
Plant, L.D., P.N. Bowers, Q. Liu, T. Morgan, T. Zhang, M.W. State, W. Chen, R.A. Kittles and Goldstein, Steve A. N.. "A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y.." J. Clin Invest 116. 1 (2006): 430-435.
Rajan, S.,L., Plant, M.L. Rabin, M.H. Butler, and Goldstein, Steve A. N.. "Sumoylation silences the plasma membrane leak K+ channel K2P1.." Cell 121. 1 (2005): 37-47.
Chen, H., Kim, L.A., Rajan, S., Xu, S and Goldstein, Steve A. N.. "Charybdotoxin binding in the IKs pore demonstrates two MinK subunits in each channel complex.." Neuron 40. 1 (2003): 15-23.
O'Kelly, I., Butler, M.H., Zilberberg, N. and Goldstein, Steve A. N.. "Forward Transport: 14-3-3 binding overcomes dibasic retention in endoplasmic reticulum by dibasic signals.." Cell 111. 1 (2002): 577-588.
Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., and Goldstein, Steve A. N.. "MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.." Cell 104. 1 (2001): 217-231.
Bockenhauer, D., Zilberberg, N. and Goldstein, Steve A. N.. "Reversible conversion of a hippocampal potassium leak into a voltage-dependent channel by phosphorylation." Nature Neurosci 4. 1 (2001): 486-491.
Sesti, F., Abbott, G. W., Wei, J., Murray, K. T., Saksena, S., Schwartz, P. J., Priori, S. G. Roden, D. M. George Jr., A. L. and Goldstein, Steve A. N.. "A common polymorphism associated with antibiotic-induced cardiac arrhythmia.." Proc. Natl. Acad. Sci. 97. 1 (2000): 10613-10618.
Abbott, G. W., Sesti., F., Splawski, I., Buck, M., Lehmann, M. H., Timothy, K. W., Keating, M. T. and Goldstein, Steve A. N.. "MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia." Cell 97. 1 (1999): 175-186.
Ketchum, K. A., W. J. Joiner, A. J. Sellers, L. K. Kaczmarek and Goldstein, Steve A. N.. "A new family of outwardly rectifying potassium channel proteins with two pore domains in tandem.." Nature 376. 1 (1995): 690-5.