Our Work
Cancer and most diseases result from abnormal cell signaling or overexpression of activated membrane proteins. The interaction of protein involved in the signaling process can be observed through using TIRF single-molecule microscopy. Understanding this mechanism can help develop more precise cancer-targeted drugs. Cancer-targeted drugs have highly selective inhibition of receptors and membrane proteins. Binding or inhibiting the activity of proteins in signal transmission to inhibit abnormal signal transmission can slow down the generation and reproduction of cells. But the problem with today's targeted drugs is that resistance develops within a year or two, and side effects effect. Therefore, after the drug is designed and administered in the plan, it is necessary to study whether membrane proteins and downstream cells produce other signals to reactivated abnormal cells can help design drugs to reduce drug resistance. In addition, how heterogeneous modulators affect signaling to understand how long-range regulation activates specific signaling pathways to reduce side effects use
Investigate signal transduction among the membrane proteins and the downstream proteins at the molecular level.
GPCRs are the largest family of membrane proteins, and 30-40% of FDA-approved drugs use GPCRs as targets which indicates that the abnormal signal transduction of GPCR highly implicates with a variety of diseases. We aim to understand how GPCR activates its downstream protein (β-arretin and etc), and to what extent the coupling of GPCR and β-arretin can regulate the downstream signaling effect of β-arretin.
Interrogate the biased signaling from the agonists in GPCR signaling.
Using TIRF microscopy to study different allosteric regulators that regulate proteins downstream of GPCRs and stimulate different
signaling pathways at the single-molecule level.
Develop New Method to Reconstitute Full-length Membrane Protein
The purification and reconstitution of the full-length transmembrane protein is always challenging. It is mostly due to the complexity of its structure. We aim to develop novel methods to extract intact membrane proteins from the live cell and in situ reconstitute them for further studies.
Capture the transient state of membrane protein
25-30% of breast cancers have HER2 protein is overexpressed. Since Her2 protein promotes cell proliferation, HER2-positive breast cancer is relatively dangerous. It is currently known that monoclonal antibodies can promote internalization leading to the degradation of Her2 protein.We aim to investigate the transient strcuture of HER2 at the single-molecule level using TIRF to provide better understanding of HER2 internalziation process.
Faciliate the design of drugs with lower or less side effects/ resistance in cancer therapy
Target the stage after the treatment to understand whether the membrane proteins and the downstream proteins in the cell can develop the compensatory mechanism reactivated the abnormal cells. This research would facilitate the design of the novel drugs in the future with the lower potential for the
development of drug resistance.