725 N. Wolfe Street
Baltimore MD 21205
Molecular Biology and Physiology of Ion Transport
Chloride is the most abundant free negatively charged ion in the body. Chloride channels are cell-membrane embedded proteins, allowing the movement of chloride in and out of the cells. Defects in chloride fluxes are responsible for many human disorders. However, we know little about some of these mysterious gate-keepers in cells.
Our Lab develops high throughput functional genomics screening approaches and has recently identified two novel chloride channels: SWELL1 volume-regulated anion channel and PAC proton-activated chloride channel. We are interested in elucidating the molecular identity, regulation, cell biological and physiological function of these novel ion channels with a focus on the nervous system (neuron and glia), and revealing their potential role in diverse neurological disease, such as ischemic stroke, pain, epilepsy and glioma. Toward that goal, we employs a multi-disciplinary approach including mouse genetics, cell and brain slice electrophysiology, biochemistry, and imaging techniques.
We are always looking for curious and motivated graduate students to join the lab. Please visit our lab page or email me to learn more about our research.
Yang J, Chen J, Liu Y, Chen KH, Baraban JM, Qiu Z. Ventral tegmental area astrocytes modulate cocaine reward by tonically releasing GABA. Neuron. 2023. S0896-6273(22)01154-0. PMID: 36681074.
Mihaljevic L, Ruan Z, Osei-Owusu J, Lü W#, Qiu Z#. Inhibition of the proton-activated chloride channel PAC by PIP2. eLife. 2023. 12:e83935. doi: 10.7554/eLife.83935. PMID: 36633397.
Osei-Owusu J, Ruan Z, Mihaljevic L, Matasic DS, Chen KH, Lü W#, Qiu Z#. Molecular mechanism underlying desensitization of the proton-activated chloride channel PAC. eLife. 2022. 11:e82955. doi: 10.7554/eLife.82955. PMID: 36547405.
Osei-Owusu J, Kots E, Ruan Z, Mihaljevic L, Chen KH, Tamhaney A, Ye X, Lü W, Weinstein H, Qiu Z. Molecular determinants of pH sensing in PAC proton-activated chloride channel. PNAS. 2022. 119(31):e2200727119. PMID: 35878032.
Osei-Owusu J, Yang J, Leung KH, Ruan Z, Lü W, Krishnan Y, Qiu Z. Proton-activated chloride channel PAC regulates endosomal acidification and transferrin receptor-mediated endocytosis. Cell Reports. 2021. 34(4):108683. PMID: 33503418.
Ruan Z*, Osei-Owusu J*, Du J, Qiu Z#, Lü W#. Structures and pH sensing mechanism of proton-activated chloride channel. Nature. 2020. 588(7837):350-354. PMID: 33149300. #Corresponding authors.
Zhou C, Chen X, Planells-Cases R, Chu J, Wang L, Cao L, Li Z, López-Cayuqueo KI, Xie Y, Ye S, Wang X, Ullrich F, Ma S, Fang Y, Zhang X, Qian Z, Liang X, Cai S, Jiang Z, Zhou D, Leng Q, Xiao TS, Lan K, Yang J, Li H, Peng C, Qiu Z#, Jentsch TJ#, Xiao H#. Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity. Immunity. 2020. pii: S1074-7613(20)30129-1. PMID: 32277911.
Yang J*, Chen J*, Vitery MDC*, Osei-Owusu J, Chu J, Yu H, Sun S, Qiu Z. PAC, an evolutionarily conserved membrane protein, is a proton-activated chloride channel. Science. 2019. 364: 395-399. PMID: 31023925.
Yang J, Vitery MDC, Chen J, Osei-Owusu J, Chu J, Qiu Z. Glutamate-releasing SWELL1 channel in astrocytes modulates synaptic transmission and promotes brain damage in stroke. Neuron. 2019. 102: 813-827. PMID: 30982627.
Qiu Z, Dubin AE, Mathur J, Tu B, Reddy K, Miraglia LJ, Reinhardt J, Orth AP, Patapoutian A. SWELL1, a plasma membrane protein, is an essential component of volume-regulated anion channel. Cell. 2014. 157: 447-458. PMID: 24725410.