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Ji-fang Zhang, PhD

Contact Dr. Zhang

900 Walnut Street
Philadelphia, PA 19107

(215) 503-5669
(215) 503-2073 fax

Research and Clinical Interests

Voltage-gated calcium channels, calcium signaling in neurons

My lab is interested in voltage-gated Ca2+ channels (VGCCs) and Ca2+ influx through VGCCs in neuronal signaling. The particular question we ask is how Ca2+ influx through different types VGCCs can specifically initiate/regulate different signaling pathways. We have focused on identification and functional characterization of novel Ca2+ channel partner proteins in neurons. The current projects include:

(1) VGCCs and Ca2+ influx in synaptic vesicle (SV) recycling. Ca2+ influx through VGCCs is essential for release of neurotransmitters. Ca2+ has also been implicated in regulation of SV endocytosis. However, the mechanisms for such regulation are not clear. We have identified a novel Ca2+ sensor in endophilin, a protein important for SV endocytosis (Cell, 2003). Binding of Ca2+ to endophilin changes its conformation and may contribute to regulation of SV endocytosis by Ca2+. Experiments are in progress to address (a) the molecular and structural nature of the novel Ca2+ sensor; and (b) the functional roles of this novel Ca2+ sensor in regulation of SV endocytosis.

(2) Distribution and trafficking of VGCCs. Different types of VGCCs have their unique subcellular distributions in neurons. Little is known of the molecular mechanisms for such distribution. We have shown that a novel VGCC partner protein, tctex1, a motor protein subunit, plays an important role in channel trafficking (Nature Neuroscience, 2005). We will continue to examine interactions between motor proteins and VGCCs; particularly focusing on (a) how such interactions can be regulated; and (b) whether such interactions may contribute to synaptogenesis.

(3) VGCCs and Ca2+ influx in regulation of gene expression, particularly in synaptic plasticity and in neurodegeneration. We will focus on several proteins, which are known to be involved in regulation of gene expression. We will test whether interactions of these proteins with VGCCs contribute to activity-dependent regulation of gene expression in neurons. The techniques that I use in my research are molecular biology, biochemistry, cell biology, electrophysiology and fluorescence imaging. Knowledge from our research will help understand the fundamentals of neurobiology and shed light on why genetic defects of VGCCs may cause certain neurological diseases.