Haifeng Yang Research
Xenograft analysis revealed that PBRM1 suppression significantly enhanced tumor growth by kidney cancer cells.
Investigating the bromodomains’ functions of PBRM1.
The bromodomains (BD domains) recognize acetylated lysine residues. We found that the BD domains of PBRM1 are required for the recognitions of acetylated K14 on histone H3 and acetylated and activated p53. We are investigating how PBRM1 mediates the signaling of H3K14Ac and activated p53 through its BD domains.
Elucidating how PBRM1 interact with VHL and which of its biological functions are disrupted by tumor-derived mutations.
We found that when VHL is mutated, the activated HIF, and JARID1C to a lesser extent, significantly impacted on PBRM1’s binding to the genome and changed its ability to influence transcription. We also found that most tumor-derived mutations disrupted PBRM1’s association with the rest of SWI/SNF complex. We seek to understand the tumor suppression mechanisms of PBRM1 and design novel therapies based on such knowledge.
Understanding the kinome changes after loss of SETD2 or BAP1.
The mutations in SETD2 and BAP1 are linked with much worse prognosis for kidney cancer patients. To find the activated kinase after SETD2 or BAP1 inactivation, SILAC labeling and Mass-spec was performed to profile kinome changes. Novel changes were found which might explain the importance of SETD2 and BAP1, and might also provide unique opportunity to treat tumors harboring these mutations.