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- UCL School of Pharmacy
- Faculty of Life Sciences
Dr Mala Shah obtained a First Class (Hons) BSc in Pharmacology from the University of Bath, followed by a PhD at the Department of Pharmacology, University College London during which time she carried out work on characterising the slow afterhyperpolarization in hippocampal neurons. She subsequently won a Wellcome International Prize Travel Research Fellowship to work in Professor Daniel Johnston’s laboratory at Baylor College of Medicine (Texas, USA) where she started her work on understanding ion channel properties and function in entorhinal cortical dendrites under physiologic and epileptic conditions. In 2004, she returned to the Department of Pharmacology, University College London as a Senior Research Fellow in Professor David Brown’s laboratory and continued her studies on the functional significance of subcellular distribution of ion channels in hippocampal and cortical neurons during normal and epileptogenic conditions through funding received from the Wellcome Trust and Epilepsy Research Foundation. In 2007 she won the prestigious MRC New Investigator Award and joined the Pharmacology Department at The School of Pharmacy as a lecturer. In 2010, she obtained the esteemed ERC Starter Independent Grant.
Voltage-gated ion channels are important determinants of neuronal excitability. The hippocampus and cortex are two key brain areas involved in normal functions such as learning and memory as well as disorders such as epilepsy. Our research interests lie in understanding how voltage-gated ion channels activated at subthreshold membrane potentials affect hippocampal and cortical cell excitability under physiological as well as epileptogenic conditions. Specific projects include:
Dendritic HCN channels and temporal lobe epilepsy:
The Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels are concentrated in the apical dendrites of hippocampal and cortical pyramidal neurons. We, and others, have demonstrated that dendritic HCN channel expression in these neurons is significantly altered following the onset of epilepsy. Further, we have shown that loss of the HCN1 subunit enhances entorhinal cortical excitabiity and increases the susceptibility to epilepsy. Our goal is to understand the molecular and cellular mechanisms by which a loss of HCN channels may lead to epileptogenesis.
Presynaptic HCN channels, Ca2+ channels and neuronal excitability
We have recently demonstrated that HCN channels are also located at certain glutamatergic synaptic terminals in the adult entorhinal cortex where, by restricting the activity of low threshold T-(CaV3.2) Ca2+ channels, they inhibit synaptic release. Using a combination of multi-photon imaging and electrophysiology, we are now investigating which neurons in particular express pre-synaptic HCN channels and whether similar molecular mechanisms regulate the trafficking and plasticity of pre- and post-synaptic HCN channels.
Axonal KV7 channels and cell excitability
Mutation in two types of KV7 subunits (KV7.2 and KV7.3) have been associated with Benign Familial Neonatal Convulsions (BFNC). Recent evidence shows that KV7 channels are targeted to the axon initial segment of hippocampal and cortical pyramidal neurons. KV7 mutations that cause BFNC impair axonal targeting of these channels. However, very little is known about the functional role of axonal KV7 channels. Our aim is to understand how modulation of axonal KV7 channels affects cell excitability and synaptic integration.
|2000||PhD||Doctor of Philosophy||University College London|
|1997||BSc Hons||Bachelor of Science (Honours)||University of Bath|