Menu
  • Find a Doctor
  • International Patients
  • Newsroom
  • Contact Us
  • Patients & Families
  • Education
  • Research
  • Departments & People
  • Donate to The Barrow

    Wu Laboratory

    Jie Wu, MD, PhD

    Laboratory Focus

    Nicotinic Acetylcholine Receptor (nAChR) Physiology, Pharmacology, and Pathophysiology

    Our laboratory studies the function and pharmacology of recombinant nAChRs transfected into a cloned cell line and natively expressed nAChRs in central nervous system neurons using patch-clamp whole-cell and single-channel recordings. By combining electrophysiology and cellular/molecular techniques, we can evaluate the cellular mechanisms of addictive drug-induced reward and dependence (nicotine, alcohol, and cannabinoid).

    Cellular and Molecular Mechanisms of Epilepsy

    Our laboratory studies the cellular and molecular mechanisms of epileptogenesis using different epileptic animal models and brain tissue from epilepsy patients. We use state-of-the-art electrophysiological techniques (intracellular recordings from brain slices and patch-clamp recordings from acutely dissociated and cultured neurons) combined with cellular and molecular biological methods. Our ongoing projects in this area include include: (1) epileptogenesis of human hypothalamic hamartoma, and (2) cellular and molecular mechanisms of epileptogenesis in an Alzheimer’s disease model.

    Cellular Mechanisms of Neurodegeneration—Interaction between Amyloid Beta Peptides (Aβ) and nAChRs

    Accumulating lines of evidence indicate that there is a significantly increase of amyloid beta in the brain of Alzheimer’s disease (AD) patients. amyloid beta deposition and aggregation are thought to be the important mechanisms that cause AD. The project will evaluate the interaction between amyloid beta and nAChRs and will provide insights for understanding of the roles of nAChRs in AD pathogenesis. It also may provide new strategies for AD therapy.

    Accomplishments

    nAChR Research

    • Characterized functional and pharmacological properties of human α7 nAChRs heterologously expressed in a human SH-EP1 cell line and in single dopaminergic (DA) neurons freshly dissociated from rat midbrain
    • Identified the roles of the nAChR beta subunits in α- heteromeric nAChR (α4 beta 2 or α4 beta 4) function and pharmacology
    • Evaluated an open-channel block mechanism of α4 beta 2 nCAhRs
    • Contributed to nAChR subtype classification in ventral tegmental area DA neurons
    • Developed new compounds to block nAChRs for smoking cessation therapy
    • Elucidated the acute and chronic effects of pathological amyloid peptides on human nAChRs
    • Identified a novel type of nAChR (α7 beta 2) in basal forebrain cholinergic neurons, revealing a high sensitivity of α7 beta 2 nAChR to pathological amyloid peptides
    • Defined a novel distribution and role of α6-nAChRs in brain reward center
    • Elucidated the mechanisms of systemic exposure to nicotine-induced glutamatergic synaptic plasticity in ventral tegmental area DA neurons
    • Identified an important circuit between the prefrontal cortex and ventral tegmental area, which underlies nicotine-induced excitation in ventral tegmental area DA neurons

    Epilepsy Research

    • Elucidated epileptogenic mechanisms (spreading depression) of hyperthermic seizures in an in vitro febrile seizure model
    • Elucidated a mechanism (down-regulation of GABAA receptor γ2 subunit) of epileptogenesis in a cholesterol synthesis inhibition model of absence epilepsy
    • Identified and characterized electrophysiological features of human hypothalamic hamartoma tissue surgically resected from patients with gelastic seizures
    • Defined GABA-induced excitation in human hamartoma neurons
    • Identified amyloid peptide-induced neural hyperexcitation/hypersynchronization

    Scientific Collaborators

    During past 10 years, our research projects have been funded by several national (NIH), state (ABRC), and commercial (Philip Morris External Research) institutions. This research has led to numerous publications, which have contributed to the nicotinic acetylcholine receptor (nAChR) field and epilepsy and neurodegenerative research. Several important scientific collaborations have been established with the following individuals and their research groups: