Dr. Bingbing Li is interested in the interface between biology and chemistry to use innovative chemical tools to dissect the complexity of cancer biology with a goal to identify novel cancer therapeutics. She is passionate about developing novel cancer therapies and is currently focused on targeting clear cell sarcoma of soft tissue (CCSST), a rare and aggressive cancer driven by the EWSR1-ATF1/CREB fusion oncogene. This fusion creates a constitutively active transcription factor and is associated with a poor prognosis, especially in metastatic cases. Her team identified PRMT5 as a novel binding partner of EWSR1-ATF1 and demonstrated, through both genetic and pharmacological approaches, that PRMT5 is a druggable vulnerability in CCSST. Among several inhibitors tested, the PRMT5 inhibitor JNJ-64619178 showed promising anti-tumor activity in vitro and in vivo. These findings suggest a potential new therapeutic strategy for a cancer with no effective targeted treatments.

In another project, she is using a combination of chemical biology and cell biology to investigate the nuclear envelope. The nuclear envelope is not only important for separating nucleus from cytosol, but also important for numerous signaling pathways involved in cancer and aging. She discovered the first small molecule called LBL1 that binds to nuclear lamins, which are type V intermediate filament proteins lying underneath inner nuclear membrane. She capitalizes this discovery to investigate the nuclear lamina-ome composition under physiologically relevant conditions using LBL1 and its chemical probes.

Building on this work, she and her team developed CG-SLENP (chemical genetics–selective labeling of existing and newly synthesized proteins), the first method enabling selective labeling of these two protein pools in living cells. Using HaloTag fused in-frame with lamin A (LA), they demonstrated that CG-SLENP can distinguish newly synthesized from pre-existing proteins. Furthermore, they applied LBL1 to probe potential differences between these two LA populations. Their findings show that LBL1 differentially modulates newly synthesized and existing LA, indicating that the assembly states of the two protein pools are distinct in living cells. The CG-SLENP method is potentially generalizable to study temporal protein dynamics for a wide range of cellular proteins.