Zhe Zhang

2018 Regional Award Finalist — Post-Doc

Zhe Zhang

Current Position:
Postdoctoral Fellow

Institution:
The Rockefeller University

Discipline:
Molecular & Cellular Biology

Recognized for: Determining the atomic structure of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel using cryo-electron microscopy. Mutations in CFTR cause cystic fibrosis, a common and lethal genetic disorder that affects mostly the lungs and digestive system.

Areas of Research Interest and Expertise:

Structural Biology, Membrane Proteins, Ion Channels, Signal Transduction, Vesicle Trafficking

Biography:

PhD, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China
BS, Shandong University, China

Dr. Zhang determined the atomic structure of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel – a structure that had proved elusive to researchers for decades. Mutations in CFTR cause cystic fibrosis, a lethal genetic disorder that primarily affects the lungs and is characterized by accumulation of dehydrated mucus and bacterial infection in the airways. Previous efforts to resolve the structure of CFTR were hampered by difficulties in purifying a stable form of the protein. Dr. Zhang overcame these challenges and successfully determined the molecular structures of both the zebrafish and human CFTR in the dephosphorylated, ATP-free conformation (closed state) using cutting-edge techniques in cryo-electron microscopy. Further, Dr. Zhang also determined the structure of zebrafish CFTR in the phosphorylated, ATP-bound conformation (flicker-closed state), providing novel insight into the major structural rearrangements associated with channel function. A better mechanistic understanding of CFTR and CFTR mutants may aid the development of new and better drugs for cystic fibrosis.

"Revealing the pathogeneses of human diseases and developing better treatments for patients are my motivations to do research. Membrane proteins are the most prevalent drug targets due to their vital roles in a variety of biological processes. I am mainly focusing on the structural studies of disease-related membrane proteins including ion channels, transporters, and receptors, in order to understand their functional mechanisms and develop effective medicines for corresponding diseases."

Key Publications:

  1. Z. Zhang, J. Chen. Atomic structure of the cystic fibrosis transmembrane conductance regulator.  Cell, 2016.

  2. F. Liu*, Z. Zhang*, L. Csanády, D.C. Gadsby, J. Chen. Molecular structure of the human CFTR ion channel.  Cell, 2017 (*equal contribution).

  3. Z. Zhang, F. Liu, J. Chen. Conformational changes of CFTR upon phosphorylation and ATP binding.  Cell, 2017.

  4. Z. Zhang*,$, B. Tóth*, A. Szollosi, J. Chen, L. Csanády$. Structure of a TRPM2 channel in complex with Ca2+ explains unique gating regulationeLife, 2018 (*equal contribution, $corresponding author).

Other Honors:

2018 Tri-Institutional Breakout Prize for Junior Investigators, Memorial Sloan Kettering Cancer Center, The Rockefeller University, and Weill Cornell Medicine
2017 – 2019 The Charles H. Revson Senior Fellowship in Biomedical Science, Charles H. Revson Foundation
2014 China National Scholarship, Chinese Ministry of Education
2014 Chinese Academy of Sciences Merit Student, Chinese Academy of Sciences

In the Media:

Science Daily - New study resolves the structure of the human protein that causes cystic fibrosis

Cystic Fibrosis News Today - 3-D Map of CF Protein Structure May Help Determine How Disease Develops

Science Daily - First structural map of cystic fibrosis protein sheds light on how mutations cause disease

Nature Structural & Molecular Biology - CFTR structure: lassoing cystic fibrosis

Rockefeller News - First structural map of the cystic fibrosis protein sheds light on how mutations cause disease

Rockefeller News - New study resolves the structure of the human protein that causes cystic fibrosis

Anatrace - Raising standards and helping others breathe easier

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