Xu, Bin, PhD

I have revealed the novel role of Steroid Receptor RNA Activator (SRA), a lncRNA, in regulating nuclear receptor transcription and function in steroidogenesis, adipocyte differentiation and promoting hepatic steatosis using cellular and mouse genetic model, and the transcription factor NKX1-2 promotes adipogenesis. I have recently shown for the first time that ASH1L histone methyltransferase is over-expressed in anaplastic thyroid cancer (ATC) primary tumors, is a potential therapy target in ATC. Cutaneous lupus erythematosus (CLE) affects up to 70% of patients with systemic lupus erythematosus (SLE), and type I interferons (IFNs) are important promoters of SLE and CLE. My current project is to identify novel regulators including IFNk and to elucidate molecular mechanism by underlying their role to cause of SLE and CLE, the use of small molecular inhibitors to treat SLE and CLE patients, and uncover a role for functional dysregulation of the Hippo signaling pathway in SLE keratinocytes (KCs) through overexpression of the apical key regulator, WW domain containing protein 1 (WWC1), and increased phosphorylation of Yes-associated protein (YAP).

My previous research has been focused on the biological function of the long noncoding RNA steroid receptor RNA activator (SRA) in adipocytes and in steroidogenesis. I have for the first time in the field discovered that SRA binds to a subset of nuclear receptors including the thyroid hormone receptor (TR) and nuclear receptor steroidogenic factor 1 (SF-1), as well as to the N-terminal region of the atypical nuclear receptor Dax1 and the nuclear receptor peroxisome proliferator-activated receptor- (PPAR), and regulates their transcriptional activity. My studies revealed important functions of SRA and Dax1 in transcriptional coactivation of SF1 in steroidogenesis and adrenal biology. I have also elucidated that SRA is expressed in mouse embryonic stem (mES) cells and is required for Dax-1 upregulating Oct4 expression in regulation of mES cell pluripotency. To assess SRA function in vivo, I for the first time generated Sra1 gene knockout mice and revealed that SRA gene knockout protects against diet-induced obesity and improves glucose tolerance. In addition, I have characterized that the transcription factor NKX1-2 promotes adipogenesis, as well as the PAX8-PPAR (PPFP) fusion protein and thyroid transcription factor 1 (TTF-1) physically interact, and that TTF-1 regulates the pro-adipogenic action of pioglitazone. Furthermore, I have recently shown for the first time that ASH1L histone methyltransferase is over-expressed in anaplastic thyroid cancer (ATC) primary tumors, is a potential therapy target in ATC. Cutaneous lupus erythematosus (CLE) affects up to 70% of patients with systemic lupus erythematosus (SLE), and type I interferons (IFNs) are important promoters of SLE and CLE. My current project is to identify novel regulators including IFNk and to elucidate molecular mechanism underlying their role to cause of SLE and CLE, and the role and use of small molecular inhibitors to treat SLE and CLE patients. More recently, I also work on the R01 project to uncover a role for functional dysregulation of the Hippo signaling pathway in SLE keratinocytes (KCs) through overexpression of the apical key regulator, WW domain containing protein 1 (WWC1), resulting in chronic overactivation of Hippo signaling and increased phosphorylation of Yes-associated protein (YAP).