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Appointments:
Professor
Department of Pediatrics
Director, Institute of Molecular
Pediatric Science
Physician-in-Chief, Comer Children's
Hospital
Committee on Molecular Medicine/MPMM
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Education:
M.D., Harvard Medical School, 1986
Ph.D., Harvard University, 1986
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Contact:
Phone: (773) 702-6205
Fax: (773)
702-6205
E-Mail:
sangoldstein@uchicago.edu
Address:
The University of Chicago
UCCH K160G (MC 8000)
5721 South Maryland Avenue
Chicago, Illinois 60637
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Related Research Interests:
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Steve A. N. Goldstein, M.D., Ph.D.
Research Summary
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 electrical signals that allow excitation of the
heart, skeletal muscle and a circulating lymphocyte; less sensational
but equally important, ion channels mediate cellular fluid and
electrolyte homeostasis. Remarkably, some fundamental questions
remain to be answered. How do they open and close? How do
inherited mutations produce cardiac arrhythmia, hypertension, seizures,
or deafness? How do drugs act on ion channels to produce
beneficial outcomes or harmful side effects? The laboratory uses
biophysical, genetic and biochemical methods to pursue four current
research directions: (1) The normal role, mechanism for
disease-association, and structure of the potassium channel accessory
subunits. (2) Discovery, cloning and function of a new superfamily of
potassium channels that produce "background leak", the K2Ps. (3)
Advancing the application of genetic tools to the function of ion
channels (an approach heralded as "proteomics") and the association of
ion channels with disease to enable diagnosis, therapy and prevention
(gene-based medicine). (4) Diagnosis and treatment strategies for
diseases of ion channels, particularly, in children.
Selected Papers
Journal Articles
Abbott
GW and Goldstein SAN. (2002). Disease-associated
mutations in KCNE
potassium channel subunits (MiRPs) reveal
promiscuous disruption
of multiple currents and conservation of mechanism. FASEB J., 16:390-400.
O'Kelly
I, Butler
MH, Zilberberg N and Goldstein SAN. (2002).
Forward Transport:
14-3-3 binding overcomes dibasic
retention in endoplasmic
reticulum by dibasic signals. Cell.,
111:577-588.
Chen H, Sesti F and
Goldstein SAN.
(2003). Pore and state-dependent cadmium block of IKs
channels formed
with MinK-55C and wild type KCNQ1
subunits. Biophys. J., 84:3679-3689.
Sesti F, Rajan S,
Gonzalez-Colaso R, Nikolaeva N, and Goldstein SAN. (2003). Hyperpolarization moves
S4 sensors inward to
open MVP, a methanococcal voltage-gated potassium channel. Nature Neurosci.,
6:353-361.
Chen H, Kim LA, Rajan S, Xu
S and Goldstein SAN. (2003). Charybdotoxin binding in the IKs pore demonstrates two MinK
subunits in each channel
complex. Neuron., 40:15-23.
Kim, L.A., Furst,
J., Butler,
M.H., Xu, S., Grigorieff, N. and S. A. N. Goldstein. (2004). Ito
channels are octameric complexes with four subunits of each K v4.2 and K+ channel-interacting
protein 2
(KChIP2). J. Biol. Chem., 279:5549-5554.
Kim
LA, Furst J, Gutierrez D, Butler MH, Xu S, Goldstein SAN and Grigorieff
N. (2004). Three
Dimensional Structure of Kv4.2–KChIP2
Channels by Electron Microscopy at 21 Å Resolution. Neuron,
41:513-519.
Rajan S, Plant LD, Rabin ML, Butler MH and Goldstein
SAN. (2005). Sumoylation
silences the plasma membrane leak K+
channel K2P1. Cell., 121:37-47.
Abbott
GW, Butler MH and Goldstein SAN. (2006). Phosphorylation and
protonation of neighboring MiRP2 sites: function and pathophysiology of
MiRP2-Kv3.4 potassium channels in periodic paralysis. FASEB J: 20
293-301.
Plant LD, Bowers PN, Liu Q, Morgan T, Zhang T, State MW,
Chen W, Kittles RA and Goldstein SAN. (2006). A common cardiac sodium
channel variant associated with sudden infant death in African
Americans. J. Clin. Invest., 116:430-435.
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Faculty and Research
Programs
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