In our research, we are focused on addressing the challenge of understanding how the hepatitis B virus interacts with host cells at the molecular level. Specifically, we aim to elucidate the structural dynamics of the virus during its life cycle. This insight is crucial for developing more effective antiviral therapies as it helps identify new targets for drug development. The part that excites us most about our research is the profound impact it has on advancing our understanding of viral diseases, specifically through the structural study of viruses using cryo-electron microscopy. We are proud to contribute to a field that not only expands the basic scientific knowledge, but also paves the way for therapeutic approaches.
We use cryo-EM to study Hepatitis B virus life cycle.
Hepatitis B virus (HBV), a small enveloped DNA virus with an RNA intermediate, is a global public health concern. About 257 million people still suffer from chronic HBV infection and approximately 884,000 people die from it annually. In our lab we use cryo-EM to obtain structural information of HBV at different stages and with the goal to make significant impacts to our understanding of HBV biology.
Our cryo-EM workflow
Research I:
Structural insights of HBV infection.
We are working with Dr. Jianming Hu at Penn State University College of Medicine to structurally characterize HBV infection inside the mammalian cells.
Additionally, we are working with Dr. Adam Zlotnick at Indiana University – Bloomington to depict the molecular mechanism of HBV reverse transcription using a combination of cryo-EM, biochemical, and biophysical analyses at different viral intermediate states.
Research II:
Molecular mechanism of alphavirus infection.
Alphavirus is a well established model for studying membrane fusion process. We aim to use cryo-EM to understand 1) how E1 and E2 envelop proteins modulate the membrane fusion at atomic resolution level and 2) how membrane fusion is related to viral infectivity. In addition, we are studying the high resolution structures of minor structural proteins of TF and 6K in alphavirus. This project is mainly collaborating with Dr. Tuli Mukhopadhyay at Indiana University – Bloomington.
Research III:
Non-perfect icosahedral capsid assembly.
Not all the icosahedral capsids are perfectly assembled. Biologically the capsid, especially in enveloped virus, may have some defects in order to trigger virus disassembly at the right time. Using icosahedral averaging would wash out such unique structural feature; thus, one might not be aware of its presence. We analyze cryo-EM structure of viral capsids without imposing any symmetry to investigate their biological relevance. We are trying to understand the asymmetric features that we observe in HBV.
Additionally. we are working with Dr. Irina Tsvetkova and Dr. Bogdan Dragnea at Indiana University – Bloomington to study unique structural organization and physical property of novel virus-like particles.
Research IV:
Human molecular chaperonin.
In collaboration with Dr. Lingling Chen at Indiana University – Bloomington, we are investigating the molecular mechanism of human mitochondrial heat shock protein 60 (mHsp60) and its complexes using cryo-EM.
