Xiaowei Hou , PHD

My research interests center on unraveling the molecular mechanisms of human diseases. It's fascinating how a single mutation in one gene can drastically alter the structure or function of its protein product, leading to various illnesses. The research in my laboratory currently focuses on the structure and function of proteins involved in Ca2+ signaling, whose malfunction can lead to immune disorders, neurodegenerative diseases, and metabolic diseases.

Maintaining an exceptionally low concentration of calcium ions (Ca2+) in the cytosol is crucial for animal cells, as it enables them to respond to changes in Ca2+ levels and trigger various cellular pathways critical for biological processes such as fertilization, neurotransmission, muscle contraction, immune response, and cell death. Ca2+ transporting proteins, such as Ca2+ channels and Ca2+ permeable receptors, located in the plasma membrane and membrane of intracellular organelles, act as gateways for Ca2+ entry, playing a central role in rapid Ca2+ mobilization and signaling.

Specifically, one of the focuses in my research program is to study the structure and function of the Ca2+ release-activated Ca2+ (CRAC) channel, which is ubiquitously expressed in nearly all cell types and plays particularly crucial roles in T cell activation during the adaptive immune response. A functional CRAC channel requires the interaction of two proteins: the Orai channel in the plasma membrane and the ER membrane protein STIM. Upon depletion of the ER Ca2+ store, STIM proteins translocate to ER-plasma membrane contact sites and recruit Orai proteins for direct interaction. STIM gated opening of the Orai channel allows Ca2+ influx into the cell, also known as the store-operated Ca2+ entry (SOCE).

As a structural biologist, I seek to understand proteins at a molecular level-- ranging from 10-1 to tens of nanometers. This level of information is critical to understanding the structural assembly and conformational states of a protein or a protein complex. For instance, an active ion channel in the cell membrane might cycle through a resting, pre-activated, activated, and inactivated state. Capturing a full set of conformational states and assessing their relationship with functional characteristics greatly help to elucidate the molecular mechanism of channel function.

Moreover, capturing a ‘zoom-in’ view of large molecular machines in the native cellular environment or under pathological conditions is critical for understanding the pathology of diseases at the molecular level. To achieve these research goals, the lab will use a combination of cell biology, biochemistry, biophysics, and structural biology (including X-ray crystallography, cryo-electron microscopy, and cryo-electron tomography). A better understanding of these molecular machines will help to accelerate biomedical research and facilitate therapeutic developments for human diseases.

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Join our growing lab! We're searching for a postdoctoral fellow passionate about uncovering mechanistic mysteries related to human disease at the molecular level. Apply now: https://jobs.uc.edu/job-invite/96945/
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PhD: University of Science and Technology of China; Institute of Biophysics, Chinese Academy of Sciences 2008 (Molecular Biology and Biochemistry; Structural Biology)

BS: Anhui University 2003 (Chemical Engineering)

Postdoc: Memorial Sloan Kettering Cancer Center New York, NY, 2022 (Structural Biology; Ion Channel Biochemistry and Biophysics)

Molecular mechanisms of human diseases; ion channels and channelopathies; cellular signaling; inter-organelle communication; protein-protein interactions; structural dynamics of macromolecular assemblies; cryo-electron microscopy

2016 -2022 Senior Research Scientist, Memorial Sloan Kettering Cancer Center, New York, NY

2008 -2016 Postdoctoral Research Fellow/Scholar/Associate, Memorial Sloan Kettering Cancer Center, New York, NY

Grant: #R35GM151170 Investigators:Hou, Xiaowei 07-03-2023 -04-30-2028 National Institute of General Medical Sciences Molecular regulation of the CRAC channel signaling pathway Role:PI 405000.00 Awarded Level:Federal

Peer Reviewed Publications

Hou, Xiaowei; Outhwaite, Ian R; Pedi, Leanne; Long, Stephen Barstow (2020. ) Cryo-EM structure of the calcium release-activated calcium channel Orai in an open conformation.eLife, , 9 , More Information

Hou, Xiaowei; Burstein, Shana R; Long, Stephen Barstow (2018. ) Structures reveal opening of the store-operated calcium channel Orai.eLife, , 7 , More Information

Hou, Xiaowei; Pedi, Leanne; Diver, Melinda M; Long, Stephen B (2012. ) Crystal structure of the calcium release-activated calcium channel Orai.Science (New York, N.Y.), , 338 (6112 ) ,1308-13 More Information

Hou, Xiaowei; Liu, Rujuan; Ross, Stuart; Smart, Eric J; Zhu, Haining; Gong, Weimin (2007. ) Crystallographic studies of human MitoNEET.The Journal of biological chemistry, , 282 (46 ) ,33242-33246 More Information

Hou, Xiaowei; Wang, Yanli; Zhou, Zhongwei; Bao, Shilai; Lin, Yajing; Gong, Weimin (2007. ) Crystal structure of SAM-dependent O-methyltransferase from pathogenic bacterium Leptospira interrogans.Journal of structural biology, , 159 (3 ) ,523-8 More Information

Hu, Pu; Sun, Lei; Zhu, Zhi-Qiang; Hou, Xiao-Wei; Wang, Shu; Yu, Shan-Shan; Wang, Hui-Li; Zhang, Ping; Wang, Ming; Niu, Li-Wen; Teng, Mai-Kun; Ruan, Di-Yun (2008. ) Crystal structure of Natratoxin, a novel snake secreted phospholipaseA2 neurotoxin from Naja atra venom inhibiting A-type K+ currents.Proteins, , 72 (2 ) ,673-83 More Information

Book Chapter

Xiaowei Hou (2018 ) Ion Channels Advances in Membrane Proteins .(pp. 17-45).Springer, Singapore.

Ion Channels

Invited Presentations

Xiaowei Hou (06-19-2022. ) Gordon Research Conference on Calcium Signaling, Ventura, CA. Level:International

Xiaowei Hou (09-23-2021. ) 74th Annual Meeting of the Society of General Physiologists: Ion Channel & Transporters in Immunity, Inflammation & Antitumor Immunity, Woods Hole, MA. Level:International

Xiaowei Hou (03-26-2021. ) Molecular Biophysics Annual Symposium at Weill Cornell Medicine, New York, NY.

Xiaowei Hou (03-05-2019. ) Biophysical Society 63th Annual Meeting, Baltimore, MD. Level:International

Xiaowei Hou (04-24-2023. ) Biochemistry and Molecular Biology Seminar Series at the University of Texas Health, Houston, TX.

Xiaowei Hou (06-12-2018. ) FASEB-Calcium and Cell Function, Lake Tahoe, CA. Level:International

Xiaowei Hou (08-01-2017. ) New York Structural Biology Discussion Group Summer Meeting, New York, NY. Level:Regional

Xiaowei Hou (02-09-2015. ) Biophysical Society 59th Annual Meeting, Baltimore, MD. Level:International

Xiaowei Hou (07-05-2014. ) Gordon Research Seminar on Ion Channels, South Hadley, MA. Level:International

Xiaowei Hou (12-06-2023. ) Biochemistry and Molecular Biology Academic Seminar Series at the University of Chicago, Chicago, IL.

Xiaowei Hou (06-17-2024. ) FASEB- Channels and Transporters in Immunity, Saint Paul, MN. Level:International

Poster Presentations

Xiaowei Hou (06-12-2023. ) 2023 FASEB-The Endoplasmic Reticulum (ER) Conference: Structure, Function and Disease, Melbourne, Florida. . Level:International

Xiaowei Hou (09-15-2022. ) 75th Annual Meeting of the Society of General Physiologists: Ion Channels in Context: Structure and function in native cells and macromolecular complexes, Woods Hole, MA. . Level:International

Xiaowei Hou (10-26-2021. ) FASEB- the Calcium and Cell Function Conference, virtual conference. . Level:International

Xiaowei Hou (08-02-2018. ) New York Structural Biology Discussion Group Summer Meeting, New York, NY. . Level:Regional

Xiaowei Hou (07-09-2018. ) Gordon Research Conference on Ion Channels, South Hadley, MA. . Level:International

Xiaowei Hou (07-06-2014. ) Gordon Research Conference on Ion Channels, South Hadley, MA. . Level:International

Xiaowei Hou (02-05-2013. ) Biophysical Society 57th Annual Meeting, Philadelphia, PA. . Level:International

Symposium

Xiaowei Hou (09-08-2023. ) Inaugural Cryo-EM Symposium .Cincinnati, OH. Level:Regional

2014 Blavatnik Regional Award Finalist in Chemistry Link: http://blavatnikawards.org/honorees/profile/xiaowei-hou/

2014 MSKCC Postdoctoral Researcher Award

Academic - 2251 Medical Sciences Building
231 Albert Sabin Way
Cincinnati  Ohio, 45267
Phone: 513-558-7827
xiaowei.hou@uc.edu