Sang Jun Han, Ph.D.
Department of Molecular and Cellular Biology
Ph.D.: Seoul National University, Korea
Postdoctoral training: Baylor College of Medicine, Houston
Modulation of In Vivo Nuclear Receptor Activity
In vivo imaging of nuclear receptor activity in mice
In order to investigate nuclear activity in mice, we generated Nuclear Receptor Activity Indicator (NRAI) mouse models. These mouse systems employ a bacterial artificial chromosome (BAC) clone containing a modified NR gene and its responsive reporter gene. The NRAI system consists of a modified NR BAC clone in which the DNA Binding Domain (DBD) of the NR was replaced with the yeast Gal4 DBD using a bacterial recombination system. A humanized green fluorescent protein (hrGFP) reporter controlled by the Upstream Activating Sequences for the Gal4 gene (UASG) was inserted in tandem with the modified NR gene. The expression profile of Gal4-NR in NRAI mice was similar to the endogenous NR expression profiles in those mice and expression of hrGFP faithfully recapitulates endogenous NR receptor activity. Thus, NRAI mice model allows determination of endogenous NR activity within specific cell types of target organs and temporal comparisons to endogenous regulators of genetic activity. Now, we have generated PR, ER alpha and ER beta Activity Indicator mice models.
Atlas for the temporal and spatial SERM effect on NR activity in vivo
In order to tissue specifically modulate NR activity in vivo, Selective NR Modulators (SNRM), such as Selective Estrogen Receptor Modulator (SERM) and Selective Progesterone Receptor Modulator (SPRM), are developed. SNRMs are synthetic nonstroidal compound that in some tissue act like as agonist but block steroid action in others. Thus, SNRM has a dynamic activity on NR function in tissue-specific manner. However, good animal model systems that could be used to investigate the dynamic properties of SNRM on NR activity are lacking. Using our NRAI mouse model, we have been making the atlas for dynamic SNRM activity on each NR function in vivo.
Screening of novel natural or synthetic ligands to tissue specifically modulate each NR activity
In addition to intact mouse model, we have been generating tissue specific immortalized primary cells from each NRAI mice to apply for the high-through screening system. We can rapidly find out new natural or synthetic ligands have tissue specific effect on specific NR activity by using tissue specific immortalized primary cells-based high through screening method.
Atlas for the change of NR activity during tissue specific cancer or disease development
NRs have been known as molecular therapeutic target for the cancer or disease treatment because NR activity significantly involved in cancer or disease development. In order to get detail correlation between them, we have generated the atlas for the dynamic change of NR activity during disease or cancer development. In order to do that, we have been generating human disease, such as endomertiosis, induced NRAI mouse and bigenic NRAI: tumor-induced mice model. Therefore, these atlases for the cancer or disease specific NR activities should shed a new light on disease and cancer treatment.
Expression of hrGFP and Progesterone Receptor (PR) in Luminal Epithelial Cells (LEC) of mammary gland of PR Activity Indicator mice in response to progesterone.
Baylor College of Medicine
One Baylor Plaza, M714B
Houston, TX 77030
- Han SJ, O’Malley BW, and DeMayo FJ. (2009). An Estrogen Receptor Alpha Activity Indicator Model in Mice. Genesis 00:1-10. PMID: 19882671
- Han SJ, Lonard DM and O’Malley BW. (2009). Multi-modulation of nuclear receptor coactivators through posttranslational modifications. Trends in Endocrinology and Metabolism 20(1):8-15. PMID: 19019695
- Han SJ, DeMayo FJ and O’Malley BW. (2007). Dynamic Regulation of Progesterone Receptor Activity in Female Reproductive Tissues. Ernst Schering Found Symp Proc. Vol. 2007/1:25-43. PMID: 18543433
- Jeong JW, Lee KY, Han SJ, Aronow BJ, Lydon JP, O'malley BW, Demayo FJ. (2007). The p160 Steroid Receptor Coactivator 2, SRC-2, regulates murine endometrial function and regulates progesterone independent and dependent gene expression. Endocrinol 148(9):4238-50. PMID: 17556502
- Han SJ, Tsai SY, Tsai M-J, and O'Malley BW. (2007). Distinct Temporal and Spatial Activities of RU486 on PR Function in Reproductive Organs of Ovariectomized Mice. Endocrinol 144(5): 2471-2486. PMID: 17303655
- Han SJ, Jung SY, Malovannaya A, Kim T, Ranz BR, Qin J, O’Malley BW. (2006). A Scoring system for the Follow up Study of Nuclear Receptor Coactivator Complexes. Nuclear Receptor Signaling 4 :e014. PMID: 16862220
- Han SJ, DeMayo FJ, Xu J, Tsai SY, Tsai M-J and O’Malley BW. (2006) Steroid receptor coactivators SRC-1 and SRC-3 differentially modulate tissue-specific activation functions of the progesterone receptor. Mol Endocrinol. 20: 45-55. PMID: 16141356
- Han SJ, Jeong J, DeMayo FJ, Xu J, Tsai SY, Tsai M-J and O’Malley BW. (2005). Dynamic cell type specificity of SRC-1 coactivator in modulating uterine progesterone receptor function in mice. Mol Cell Biol 25:8150-8165. PMID: 16135805
- Ye X, Han SJ, Tsai SY, DeMayo FJ, Xu J, Tsai M-J and O'Malley BW. (2005). Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice. PNAS 102:9487-9492. PMID: 15983373
- Han SJ, Lee YC, Gim BS, Ryu G-H, Park SJ, Lane WS and Kim Y-J. (1999). Activator-Specific Requirement of Yeast Mediator Proteins for RNA Polymerase II Transcriptional Activation. Mol Cell Biol 19:979-988