Publications
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Modulation of closed−state inactivation in Kv2.1/Kv6.4 heterotetramers as mechanism for 4−AP induced potentiation Ghent University University of Antwerp
The voltage-gated K+ (Kv) channel subunits Kv2.1 and Kv2.2 are expressed in almost every tissue. The diversity of Kv2 current is increased by interacting with the electrically silent Kv (KvS) subunits Kv5-Kv6 and Kv8-Kv9, into functional heterotetrameric Kv2/KvS channels. These Kv2/KvS channels possess unique biophysical properties and display a more tissue-specific expression pattern, making them more desirable pharmacological and therapeutic ...
$K_{v}2.1$ and silent $K_{v}$ subunits underlie the delayed rectifier $K^{+}$ current in cultured small mouse DRG neurons University of Antwerp
Silent voltage-gated K+ (Kv) subunits interact with Kv2 subunits and primarily modulate the voltage dependence of inactivation of these heterotetrameric channels. Both Kv2 and silent Kv subunits are expressed in the mammalian nervous system, but little is known about their expression and function in sensory neurons. This study reports the presence of Kv2.1, Kv2.2, and silent subunit Kv6.1, Kv8.1, Kv9.1, Kv9.2, and Kv9.3 mRNA in mouse dorsal root ...
Insights from zebrafish deficiency models to understand the impact of local thyroid hormone regulator action on early development KU Leuven
Thyroid hormones (THs) stimulate and coordinate a wide range of processes to ensure normal development, mainly by binding of the most active TH 3,5,3'-triiodothyronine (T3) to nuclear receptors resulting in changes in gene transcription. Local TH action is monitored at three distinct levels by different types of regulators: transmembrane transporters (TH influx and efflux), deiodinases (TH activation and inactivation) and nuclear receptors (TH ...
Prospective, real-time monitoring of pegylated Escherichia coli and Erwinia asparaginase therapy in childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma in Belgium University of Antwerp KU Leuven Vrije Universiteit Brussel Ghent University
Asparaginase (ASNase) is an important anti-leukaemic drug in the treatment of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL). A substantial proportion of patients develop hypersensitivity reactions with anti-ASNase neutralising antibodies, resulting in allergic reactions or silent inactivation (SI), and characterised by inactivation and rapid clearance of ASNase. We report results of a prospective, real-time ...
Auxiliary KCNE subunits modulate both homotetrameric Kv2.1 and heterotetrameric Kv2.1/Kv6.4 channels University of Antwerp
The diversity of the voltage-gated K+ (Kv) channel subfamily Kv2 is increased by interactions with auxiliary beta-subunits and by assembly with members of the modulatory so-called silent Kv subfamilies (Kv5-Kv6 and Kv8-Kv9). However, it has not yet been investigated whether these two types of modulating subunits can associate within and modify a single channel complex simultaneously. Here, we demonstrate that the transmembrane beta-subunit KCNE5 ...
Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders KU Leuven University of Antwerp Ghent University
Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71 patients and review 130 previously reported patients. We found that (i) encephalopathies with infantile/childhood onset epilepsies (≥3 months of age) occur almost as often as those with an early infantile onset (<3 months), and are thus more ...
Uncovering the epigenetic landscape of cell fate reprogramming and X chromosome reactivation KU Leuven
In this thesis, I aimed to define the dynamics and the mechanisms that orchestrate the reversal of stable gene silencing during reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). I used X chromosome reactivation as a paradigm to better understand the reversal of silent chromatin. In addition, my goal was also to define the gene regulatory logic of mammalian pre- implantation development and reprogramming, as well as to ...
A combined mechanistic and computational study of the gold(I)-catalyzed formation of substituted indenes Ghent University
Substituted indenes can be prepared after a sequence [1,3] O-acyl shift-hydroarylation-[1,3] O-acyl shift. Each step is catalyzed by a cationic NHC-Gold(I) species generated in situ after reaction between [(IPr) AuOH] and HBF4 center dot OEt2. This interesting silver-free way is fully supported by a computational study justifying the formation of each intermediate.