Dr. Sun has broad research experience and expertise in cancer biology and mouse genetics. Since his cloning in 1999 of SAG (Sensitive to Apoptosis Gene) (MCB, 1999), also known as RBX2, a RING component of SCF (Skp1-Cullins-F box proteins) E3 ubiquitin ligase, Dr. Sun’s laboratory has studied this key molecule, including its stress responsiveness, biochemical activity, and its roles in embryonic development and tumorigenesis, along with studies on SAG-associated F-box proteins, including β-TrCP, FBXW7 and FBXW2. Specifically, his laboratory characterized several biologically significant proteins as novel substrates of SAG-SCF E3 ligase, including procaspase-3 (Neoplasia, 2006); c-Jun (Cancer Res, 2007); HIF-1α (Oncogene, 2008); p27 (Carcinogenesis, 2008); IκBα (JCB, 2007, Free Rad Biol Med, 2010); NOXA (Clinic Cancer Res, 2010, 2017); DEPTOR (Mol. Cell, 2011); NF1 (Dev. Cell, 2011); Erbin (JCB, 2015), XRCC4 (Mol Cell, 2016), MFN1 (JCI Insight, 2019), SHOC2 (Cell Reports, 2019), β-Catenin (Nat Commun. 2019), ASCT2 (Nat Commun. 2022a) and MSX2 (PNAS, 2019b). His lab also used conditional knockout mouse models to study the role of Sag in KrasG12D-induced tumorigenesis in the lung (JCI, 2014); the skin (JCB, 2015), in prostate tumorigenesis induced by Pten-loss (Mol Cancer, 2016), and in angiogenesis (Dev Cell, 2011, Oncogene 2014). Recently, his lab showed that conditional Treg deletion of Rbx1 or Ube2m caused fetal inflammatory disorders in mice, demonstrating that neddylation E2 and E3 are essential for the maintenance of Regulatory T cell fitness (Nat Communs, 2022b). Furthermore, his lab has found that inhibition of protein neddylation would regulate stem cell proliferation and differentiation (PNAS, 2016), reprogram energy metabolism (JCI Insight, 2019) and inhibit cilia formation (Protein & Cell, 2019); FBXW2 regulates growth and migration/invasion of lung cancer cells (Nat Commun. 2017, 2019), stem cell property and drug resistance (PNAS 2019b); negative cross-talk between two neddylation E2s UBE2M and UBE2F (Mol. Cell, 2018); and negative cross-talk between RAS and mTORC1 signals, controlled by FBXW7 (Cell Reports, 2019); FBXW7 mediates early DNA damage response (NAR, 2019); and LSD1 promotes FBXW7 degradation (PNAS, 2019a). Dr. Sun has established himself as one of international leaders in the field of cullin-RING ligase and protein neddylation.
