Physiology & Biophysics

Tingwei Mu, PhD
Assistant Professor
PhD, Biochemistry, California Institute of Technology
BS, Chemistry, University of Science & Technology of China
View Curriculum Vitae (pdf)

School of Medicine E513
10900 Euclid Ave
Cleveland, OH 44116-4970
Phone: 216-368-0750
Fax: 216-368-5586

Research Interests

Understanding ion channel proteostasis

My laboratory aims to understand ion channel protein homeostasis (proteostasis) in vivo. We focus on studying gamma-aminobutyric acid type A (GABAA) receptors and potassium channels, KCNH2. Mutations in ion channels can lead to protein misfolding and extensive ER-associated degradation (ERAD), causing ion channel diseases, such as idiopathic epilepsy and cardiac arrhythmias, due to a lowered concentration of ion channels in cell membranes and thus loss of function. We explore how molecular chaperones, folding enzymes and other important protein factors coordinate to facilitate ion channel folding, degradation and trafficking. We also use small molecules to correct misfolded ion channels, as a therapeutic strategy to treat epilepsy and cardiac arrhythmias.

GABAAR protein homeostasis in the cell

GABAA receptors maintain a delicate balance between protein synthesis, folding, trafficking and degradation. Mutations in GABAA receptors resulted in extensive endoplasmic-reticulum associated degradation. Molecular chaperones and ERAD factors play a key role in regulating GABAA receptor proteostasis in the cell.

Specific Projects
  1. Understanding the Molecular Mechanism of Ion Channel Folding in the Cell.

    Because ion channel structures are extremely difficult to determine and their activity is coupled to other proteins in complicated cellular interaction networks, the molecular mechanism of ion channel folding in the cell has been elusive. Using representative members from both the ligand-gated ion channel family, such as GABAA receptors, and the voltage-gated ion channel family, such as KCNH2 potassium channels, we aim to reveal the protein homeostasis network that control ion channel folding and trafficking using proteomics and cell biological techniques.

  2. Ameliorating Ion Channel Misfolding Diseases.

    Aberrant ion channel functions lead to diseases called channelopathies. We focus on channelopathies resulting from protein misfolding and thus reduced receptor surface expression and compromised function. This defective protein trafficking has been reported to result in many channelopathies including epilepsy and cardiac arrhythmias. Epilepsy is a common neurological disease that affects 1% of the population in the United States. We focus on developing multiple strategies to discover small molecules that enhance proper ion channel folding to ameliorate epilepsy. We also explore the mechanism of action of these small molecules: how they alter the signaling pathways associated with the protein homeostasis network for disease intervention. Ultimately, we aim to develop novel therapeutic strategies for channelopathies resulting from protein misfolding.

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