After spending five years or so doing computational biophysics research in Prof. Jianhan Chen's lab, I have successfully completed my PhD dissertation defense and officially become a PhD in computational biophysics. 
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After finishing my 3-month internship at Merck, I attended the annual ResearchFest event held by the Chemistry department of UMass Amherst. I was selected as one of four presenters in this event to represent research in the department. I won the second place for the presentation and was awarded the Dr. Paul Hatheway Terry Endowment Award as first-runner up 
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In this short review, we summarize recent progresses toward understanding the structural basis of TRP channel function, as well as potential ligand binding sites that could be targeted for therapeutics. 
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Transmembrane ion channels frequently regulate ion permeation by forming bundle crossing of the pore-lining helices when deactivated. The resulting physical constriction is believed to serve as the de facto gate that imposes the major free energy barrier to ion permeation. Intriguingly, many ion channels also contain highly hydrophobic inner pores enclosed by bundle crossing, which can undergo spontaneous dewetting and give rise to a “vapor barrier” to block ion flow even in the absence of physical constriction. Using atomistic simulations, we show that hydrophobic gating and bundle-crossing mechanisms co-exist and complement one another in the human TRPV4 channel. In particular, a single hydrophilic mutation in the lower pore can increase pore hydration and reduce the ion permeation free energy barrier by about half without affecting the bundle crossing. We believe that hydrophobic gating may play a key role in other bundle-crossing ion channels with hydrophobic inner pores. 
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The original research proposal (ORP) is an exam designed to test the ability of graduate students to identify significant scientific questions, to develop research proposals based on rationalized and well-reasoned hypotheses, and, most importantly, to successfully defend the proposal. 
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CBI program (Chemistry-Biology Interface) is a highly competitive UMass-funded and NIH-funded fellowship, aiming to train students from different backgrounds to advance scientific research “at the interface of chemistry and biology”. 
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The Biophysical Society (BPS) annual meeting is held by the international biophysics society, aiming at leading, disseminating, and advancing knowledge in biophysics. 
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After a year-long remote study in China, I finally arrived in the U.S. and met with Chen lab members! 
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