Steven Z. Chou, Ph.D.Assistant Professor of Molecular Biology and Biophysics
- Education & Training
- Research Opportunities
- Lab Rotations
Our lab is part of the Department of Molecular Biology and Biophysics at UConn Health and is located on the 3rd floor of the Laboratory Building (L3080).
We are committed to discovering new knowledge in actin-based cell motility, cell division, and transmembrane signaling. Our basic research will enable scientists including ourselves to develop better therapies using protein engineering to treat, mitigate or cure musculoskeletal disorders, cardiomyopathies, blood disorders, microbial infections, developmental abnormalities, and tumors.
We are also committed to helping each lab member build a strong skill set to advance their career. To that goal, we design different research projects, provide support in fellowship/grant applications, and encourage lab trainees to attend professional conferences.
Our lab welcomes all people, regardless of gender, age, ethnicity, sexual orientation, or religion.
|Ph.D.||Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences||Biochemistry and Molecular Biology (NMR and XRD)|
|Postdoctoral||Life Sciences Institute, University of Michigan, Ann Arbor||Postdoctoral Research Fellow, Cryo-EM and Obesity|
|Postdoctoral||Department of Molecular, Cellular & Developmental Biology, Yale University||Postdoctoral Associate, Cryo-EM and Cytokinesis|
|Associate Research Scientist||Department of Molecular, Cellular & Developmental Biology, Yale University||Cryo-EM and Cell Motility|
Our research is focused on the structural basis of the following three cellular processes in health, and protein engineering for treating related diseases:
1. Actin-Based Cell Motility
Actin participates in many cell motile events in both health (e.g., muscle contraction, cell migration, cell division, cell shape maintenance) and disease (e.g., cardiomyopathy, cancer invasion, microbial pathogenesis).
Ongoing projects: red blood cell shape maintenance; nucleation of actin filaments by formins; interactions between the actin cytoskeleton and pathogenic proteins from Listeria, Plasmodium, and Borrelia.
Cytokinesis, the last step of cell division, is characterized by constriction of the actin-myosin contractile ring. During the division of one mother cell into two daughter cells, mutations in the cytokinesis proteins can cause severe problems (e.g., tumor and infertility). The final goal of this research is to recapitulate this process in vitro and to provide clues to correct or remove the mutations.
Ongoing projects: assembly and regulation of contractile ring by molecular machineries; disassembly of the contractile ring by oxidases.
3. Transmembrane Signaling
This process starts with the binding of an extracellular molecule to the integral membrane receptor. The subsequent transduction of this information across the cell membrane translates the extracellular binding event to one or more intracellular signals that alter the behavior of the target cell. Mutations in the extracellular molecule, the receptor, or intracellular binding proteins can cause abnormal signal transduction, which is quite common in tumors, leukemia, and developmental defect. Structure-based engineering of extracellular proteins combined with directed evolution is proven to be effective to alter the signaling, and targeted protein degradation can be used to remove the mutated proteins.
Ongoing projects: receptors for regulation of meiosis and mitosis in mammalian and yeast cells; receptors for neuronal development.
The major methods employed in our lab are molecular cloning, protein expression (in bacterial, yeast, insect, and mammalian cells) and purification (from both cultured cells and natural sources), cryogenic electron microscopy (single-particle, helical reconstruction, and tomography), confocal fluorescence microscopy, structure-based and evolution-based protein engineering, and targeted protein degradation.
Visiting Scholars or Students
Yes. Please contact Dr. Steven Chou at email@example.com to discuss the details of your visiting plan and research program.
Yes. Highly motivated candidates are invited to apply for a 3-year postdoc position in our lab (with the potential to extend after the 3rd year). The successful candidate must hold a terminal degree, e.g., Ph.D. or M.D., and is expected to have strong training in one or more of the following areas: protein over-expression in insect/mammalian cells, (fission) yeast genetics, (membrane) protein biochemistry, actin cytoskeleton, and cytokinesis. Former experience in structural biology (cryo-EM/ET, crystallography, and/or NMR) is a plus. To apply, please send your documents (cover letter describing your research interests and career goals, current CV, publication list, and contact information of two to three references) to Dr. Steven Chou at firstname.lastname@example.org. Informal inquiries are welcomed and should be directed to the same email address listed above.
Yes. Ph.D., M.D./Ph.D., or D.M.D./Ph.D. students, who are interested in our research projects and have a strong desire to pursue a career in basic and/or translational medicine, are welcome to join our lab.
Yes. Undergrads are always welcome to join our lab and are expected to take an independent and short-term project under the guidance of the lab PI and other members.
Accepting Lab Rotation Students: Summer 2022, Fall 2022, and Spring 2023
Lab rotation projects:
- Red blood cell shape maintenance; nucleation of actin filaments by formins; interactions between the actin cytoskeleton and proteins from pathogens.
- Assembly and regulation of contractile ring by molecular machineries; disassembly of the contractile ring by oxidases.
- Receptors for regulation of meiosis and mitosis in mammalian cells and yeast cells; receptors for neuronal development.
Mechanism of actin filament branch formation by Arp2/3 complex revealed by a high-resolution cryo-EM structureof the branch junction.
Proceedings of the National Academy of Sciences of the United States of America 2022 Dec;119(49):e2206722119
Structural basis for polarized elongation of actin filaments.
Proceedings of the National Academy of Sciences of the United States of America 2020 Dec;117(48):30458-30464
Cryo-electron microscopy structures of pyrene-labeled ADP-Pi- and ADP-actin filaments.
Nature communications 2020 Nov;11(1):5897
Mechanism of actin polymerization revealed by cryo-EM structures of actin filaments with three different bound nucleotides.
Proceedings of the National Academy of Sciences of the United States of America 2019 Mar;116(10):4265-4274
Conformational changes in Arp2/3 complex induced by ATP, WASp-VCA, and actin filaments.
Proceedings of the National Academy of Sciences of the United States of America 2018 Sep;115(37):E8642-E8651
Ligand-induced architecture of the leptin receptor signaling complex.
Molecular cell 2012 Nov;48(4):655-61
|Title or Abstract||Type||Sponsor/Event||Date/Year||Location|
|Mechanism of actin filament branch formation by Arp2/3 complex revealed by a high-resolution cryo-EM structure of the branch junction.||Poster||Gordon Research Conference||2022||Andover, NH|
|High resolution structures of actin filaments labeled with pyrene on cysteine 374||Talk||Yale University||2020||New Haven, CT|
|Sorting filament particles based on helical rise and twist improves map resolution||Talk||Yale University||2020||New Haven, CT|
|Polymerization and activation mechanism of actin filaments revealed by cryo-EM structures in different nucleotide states||Talk||Yale University||2018||New Haven, CT|
|Mechanism of actin polymerization revealed by cryo-EM structures of actin filaments with three different bound nucleotides||Poster||Gordon Research Conference||2018||Newport, RI|
|Cryo-EM structure of the super helix formed by von Willebrand factor N-terminal domains||Talk||Life Sciences Institute, University of Michigan||2015||Ann Arbor, MI|
|Structural and biochemical insights into the substrate specificity of ubiquitin C-terminal hydrolases||Talk||Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences||2010||Shanghai, China|
|Solution Structure Determination of Proteins||Talk||Institute of Organic Chemistry, Chinese Academy of Sciences||2009||Shanghai, China|
|Structural basis for the differential ubiquitin binding of the UBA domains of human c-Cbl and Cbl-b||Talk||School of Life Sciences, Fudan University||2008||Shanghai, China|