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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:
Y. Wang, F. Sesti
(2007) The molecular mechanisms underlying KVS-1-MPS-1 complex
formation. Biophys. J. in press.
K. H. Park, F.
Sesti (2007). An An arrhythmia susceptibility gene in Caenorhabditis
elegans. In press in JBC.
S.-Q. Cai and
F. Sesti (2007). A new mode of regulation of N-type inactivation
in a Caenorhabditis elegans voltage-gated potassium channel.
In press in JBC
S.-Q. Cai, W.
Li, F. Sesti (2007) Multiple modes of A-type Potassium
current regulation. Invited review. In press in Current
Pharmaceutical Design
L. Hernandez,
K.H. Park, S-Q. Cai, L. Qin, N. Partridge, F. Sesti (2006)
The antiproliferative role of ERG K+ channels in rat osteoblastic
cells. Cell Biochem. Biophys. In press.
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
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
Park, K.H., Hernandez,
L., Cai, S.Q., Wang, Y. and Sesti, F. (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
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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