Research Discoveries

Translating structure-function to therapeutics:

1. How are ions and lipids transported through cell membranes?

A. Calcium-activated chloride channels

B. Calcium-activated lipid scramblases

  • Subdued is a new calcium-activated lipid scramblase with non-selective channel functions in Drosophila (Le, et al, JBC, 2019)

2. What are the biological functions of ion and lipid transport in health and disease?

A. Calcium-activated chloride channels

B. Calcium-activated lipid scramblases

  • TMEM16F, a calcium-activated ion channel and lipid scramblase, plays a critical role in blood coagulation (Yang, et al, Cell, 2012)

  • TMEM16F-mediated phosphatidylserine exposure is critical for placental trophoblast fusion and placental development. (Zhang et al. Sci. Adv., 2020)

C. BK channelopathy

  • Seventeen years after discovering the D434G mutation in the BK channel linked to absence seizures and dyskinesia, we studied it using a knockin mouse model. This model mirrored clinical symptoms, revealed neuronal bases, and suggested a therapeutic approach for the channelopathy. (Dong, et al, PNAS, 2022).

  • Collaborating with the Mikati lab and the Cui lab, we identified and characterized a novel BK gain-of-function mutation that causes dystonia (Zhang, et al, Mov. Disord. , 2020)

D. PIEZO1 channelopathy and TMEM16F lipid scrambling

3. How can we precisely target ion and lipid transport to treat diseases?

4. Method development