RESEARCH
We apply proteomics to dissect cell signaling and we bear these principles in mind:
No protein works for nothing.
No protein works alone.
No protein works without regulation.
Proximity and Affinity Proteomics
The signaling activities of a protein often depend on its location and interactions with other proteins. We develop novel approaches employing proximity and affinity proteomics to dissect the environs of proteins/cellular compartments of interest. We have established a state-of-art proteomics-chemical biology pipeline that investigates protein-protein interactions, molecular interfaces, as well as post-translational modifications in health and disease. The toolsets have empowered us to tap into cell differentiation, carcinogenesis, and senescence (Wang, et al. 2018, Anal Chem; Xie, et al., 2019, JACS; Liu, et al. 2022, etc.). We aim to define new mechanisms, identify novel targets, and screen for new drugs.
Protein-RNA interactions
The interaction between RNA and RNA binding proteins (RBPs) dictates the function and fate of RNA molecules. Despite the growing appreciation of the functional importance of RBPs, significant technical limitations exist in elucidating RNA-protein interactions in living cells. We developed CRISPR-Assisted RNA-Protein Interaction Detection (CARPID), which leverages CRISPR/CasRx-based RNA targeting and proximity labeling to identify binding proteins of specific lncRNAs in native cellular context (Yi et al., Nature Methods, 2020). CARPID proves to be a reliable and robust method to discover the binding proteins of lncRNA inside living cells. Our research continues in the directions of refining CARPID and applying it to delineate binding proteins of various RNAs, especially lncRNAs. We focus on several lncRNAs that are implicated in cell stemness and cancer.
Non-conventional roles of immunoglobulins
Conventionally, B cells/plasma cells of the immune system are considered as the sole source of immunoglobulins (Ig), which are well known to function as antibodies. However, we have identified that a variety of non-conventional roles of Ig molecules with distinct features, e.g. tumor-derived Ig in carcinogenesis (Tang et al. 2018) and Ig-associated proteome in atherosclerosis and infarction(Tan et al. 2022) . Our understanding about the Ig molecules has since expanded to new fronts. Currently, we are conducting collaborative works that aim to fully define the non-conventional sources/roles of Ig molecules using proteomics. Such efforts may discover novel Ig-biomarkers for human diseases.
WNT signaling in homeostasis
Wnt signaling has essential roles in tissue homeostasis. We aim to define novel molecular and functional events of the role of Wnt signaling pathways in homeostasis. The directions include:
1. How Wnt signaling regulates the changes in cell polarity during carcinogenesis and metastasis.
2. How Wnt signaling coordinates cell plasticity in the differentiation of adipose tissue.