Wu Laboratory

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Wu Laboratory


 

Jie Wu, MD, PhD
Director, Neurophysiology Laboratory
Professor, Division of Neurology
Curriculum Vitae 

 

Laboratory Focus

Nicotinic Acetylcholine Receptor (nAChR) Physiology, Pharmacology, and Pathophysiology
Dr. Wu and his team are studying the function and pharmacology of heterologously expressed nAChRs in cloned cells and native nAChRs in neurons isolated from brain tissue. Using electrophysiological techniques, including patch-clamp recordings from single neurons (fresh dissociation and primary culture) and from brain slices, field recordings from brain slices, and extracellular single-unit recordings from in vivo animals (anesthetized rodents) combined with cellular and molecular techniques, we are working to elucidate the mechanisms of nicotine reward, dependence and addiction.

Cellular and Molecular Mechanisms of Epilepsy
The cellular and molecular mechanisms of epileptogenesis in animal models and in the brain tissue of human epileptic patients are other areas of focus. Cutting-edge electrophysiological techniques, combined with cellular and molecular biological methods, are used in this investigation.

Cellular Mechanisms of Neurodegeneration—Interaction between Amyloid Beta Peptides (Aβ) and nAChRs
Considerable evidence suggests that Aβ is increased in the brain of Alzheimer’s disease patients and Aβ deposition and aggregation are thought to be important mechanisms underlying Alzheimer’s disease. We are studying the interaction of these peptide sequences with natively expressed nAChR populations to provide new avenues for therapy in patients suffering from Alzheimer’s disease.

Adenosine Triphosphate (ATP)-sensitive Potassium (KATP) Channels: Physiology Pharmacology and Pathophysiology
The KATP channel is a type of potassium channel that is modulated by intracellular ATP levels. The KATP channels play important roles in neuroprotection and neurodegeneration. We are using the patch-clamp method to evaluate a variety of novel compounds that show significant potential for development into the new drugs for the treatment of Parkinson’s disease and diabetes. Current work is focused on tetrahydroprotoberberine analogs and iptakalim.

Selected Publications

Laboratory Team

 

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 research. Several important scientific collaborations have been established with the following individuals and their research groups:

  • Dr. Ronald J. Lukas (BNI, Neurobiology)
  • Dr. David Trieman (BNI, Neurology)
  • Dr. John F. Kerrigan (BNI, Pediatric Neurology)
  • Dr. Vinodh Narayanan (BNI, Pediatric Neurology)
  • Dr. Joseph Rogers (Banner Sun Health Research Institute, L.J. Roberts Center for Alzheimer's Research)
  • Professor Michael Sheiks (ASU, Department of Chemical Engineering)
  • Professor Paul St. John (University of Arizona, Department of Anatomy and Neurobiology)
  • Professor Pei Tang (University of Pittsburg School of Medicine, Department of Anesthesiology)
  • Professor Makoto Wakui (Hirosaki University School of Medicine, Japan)
  • Professor Gang Hu (Nangjing Medical University, P.R. China, Neurobiology Research Institute)
  • Professor Jianxin Shen (Shantou University Medical School, Department of Physiology)
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