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Research
Interests:
Physiology, structure
and function of potassium channels, role of potassium channels
in causing disease.
Description:
Ion-channels are
membrane proteins that control a large number of biological
functions. They modulate the activity of excitable cells
and shape signaling events in non-excitable cells such as
hormone and transmitter release.
The research of
the laboratory is focused on understanding the properties
and the role of potassium channels expressed in human heart
and in the nervous system of the nematode C. elegans.
IKr is an important
repolarizing potassium current in human ventricle. The crucial
role of this current is corroborated in a subset of patients
with congenital and acquired prolongation of the QT interval
that predisposes to a specific form of polymorphic ventricular
tachycardia known as Long QT syndrome (LQTs). A common cause
of acquired LQTs is a side effect of common medications
of diverse therapeutic and structural classes. Most of these
medications block IKr leading to delayed repolarization.
Ongoing research employs a multidisciplinary approach (genetics,
electrophysiology, molecular biology, biochemistry) to investigate
the molecular bases for IKr susceptibility to unspecific
medications in patients with drug-induced arrhythmia.
Deciphering mechanisms
of nervous system function is a major focus of current neuroscience
research. Invertebrate model systems are making a significant
contribution to this effort since many details of basic
neuronal function are remarkably conserved. The comparative
simplicity of C. elegans invites a comprehensive description
of the development, structure and function of the entire
nervous system. Recently, we have cloned and expressed functionally
a voltage-gated potassium channel, KVS, expressed in C.
elegans nervous system. The recent discovery of this channel
put us in a unique position to study mechanisms of sensory
perception, information integration and cognition.
Selected/Recent
Publications:
F. Sesti
, S. Liu and S-Q Cai "Oxidation of
K + channels by ROS: a general mechanism of aging and neurodegeneration?”
(2009). Trends in Cell Biology, DOI: 10.1016/j.tcb.2009.09.008
PDF
S-Q. Cai &
F. Sesti (2009). Oxidation of a potassium
channel causes progressive sensory function loss during
aging. Nat. Neurosci. , 12 (5):611-7.
PDF
News
linked to this publication:
1.
http://stke.sciencemag.org/cgi/content/abstract/sigtrans;2/69/ec152
2.
http://portekey-j.blogspot.com/2009/05/oxidation-of-potassium-avenue-in.html
3.
http://www.news-medical.net/news/Oxidation-of-potassium-channel-in-cells-linked-to-loss-of-neuronal-function-in-aging.aspx
4.
http://www.mycentraljersey.com/article/20090602/HEALTH/906020311
5.C&E
news 1
S-Q. Cai, Y. Wang,
K-H. Park, X. Tong, Z. Pan and F. Sesti
(2009). Auto-phosphorylation of a voltage-gated K + channel
controls non-associative learning. EMBO J. 28
(11):1601-10.PDF
W. Tutak, Ki-Ho
Park, G. Fanchini, A. Vasilov, N. Partridge, F.
Sesti , M. Chhowalla (2009). Toxicity induced enhanced
extracellular matrix production in osteoblastic cells cultured
on single walled carbon nanotube networks. Nanotechnology
, 20 (2009) 255101. doi:10.1088/0957-4484/20/25/255101.
L.
Hernandez, K. Park, F. Sesti (2009). Electrophysiological
recordings in C. elegans nervous and muscle tissue.
In Recent Advances in the Neurophysiological Basis of disease
and Addiction (edited by Huerta, M.) In press.
Y. Wang, F.
Sesti (2007). The molecular mechanisms underlying
KVS-1-MPS-1 complex formation. Biophys. J. 93(9):3083-91.
K. Park, F.
Sesti (2007). An arrhythmia susceptibility gene
in Caenorhabditis elegans. J. Biol. Chem . 282(27):19799-807.PDF
S. Cai and F.
Sesti (2007). A new mode of regulation of N-type
inactivation in a Caenorhabditis elegans voltage-gated
potassium channel. J. Biol. Chem . 282(25):18597-601.
S. Cai, W. Li,
F. Sesti (2007). Multiple modes of A-type
Potassium current regulation. invited review. Current
Pharmaceutical Design . 13:3178-84.
L. Hernandez,
K.H. Park, S-Q. Cai, L. Qin, N. Partridge, F. Sesti
(2007). The antiproliferative role of ERG K + channels
in rat osteoblastic cells. Cell Biochem. Biophys.
47(1):199-208.
S-Q. Cai, K. H.
Park, F. Sesti (2006). An evolutionarily
conserved family of accessory subunits of K+ channels. Invited
review. Cell Biochem. Biophys. 46(1):91-100. PDF
M. Chhowalla,
H E. Unalan, Y. Wang, Z. Iqbal, K. H. Park and F.
Sesti (2005). Irreversible blocking of ion channels
using functionalized single-walled carbon nanotubes. Nanotechnology
16 (2005) 2982-2986.
S-Q. Cai, L. Hernandez,
Y. Wang, K. H. Park, F. Sesti "MPS-1
is a K+ channel ?-subunit and a serine/threonine kinase.
(2005). Nat. Neurosci. 8(11):1503-9. PDF
see article entitled
"More than just pores, pg. 34-5
Ion
Channels and Nanotubes
Park, K.H., Hernandez,
L., Cai, S.Q., Wang, Y. and F. Sesti, (2005)
A Family of K+ Channel Ancillary Subunits Regulate Taste
Sensitivity in Caenorhabditis elegans. J Biol Chem, 280,
21893-21899.
Yi Wang, Ki Ho
Park, Leonardo Hernandez, Shi-Qing Cai, Federico
Sesti. Biophysical and Biomedical Aspects of KCNE
Potassium Channel Ancillary Subunits" Book chapter
Review. Recent Res. Dev. Biophys. 3(2004):1-12. ISBN: 81-7895-130-4
Ki-Ho Park, Suk-Mei
Kwok, Chetna Sharon, Rebecca Baerga, Federico Sesti. N-glycosylation-dependent
block is a novel mechanism for drug-induced cardiac arrhythmia.
(2003) FASEB J. Dec;17(15):2308-9. PDF
Ki Ho Park, Manish
Chhowalla, Zafar Iqbal, and Federico Sesti, Single-walled
carbon nanotubes: A new class of ion-channel blockers. (2003)
JBC Dec 12;278(50):50212-6
L. Bianchi, S-M.
Kwok, M. Driscoll, and F. Sesti. A potassium
channel-MiRP complex controls chemosensation in C. elegans.
(2003) JBC 278(14): 12415-24
F. Sesti,
S. Rajan, R. Gonzalez-Colaso, N. Nikolaeva, and
S. A. N. Goldstein. Hyperpolarization moves S4 sensors inward
to open MVP, a methanococcal voltage-gated potassium channel.
(2003). Nat. Neurosci. 6(4): 353-361
Molecular Basis
of Physiology
Physiology and Neurobiology
Cellular and Molecular Pharmacology
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