- Associate Professor
Mol & Cell Biology-Mol.Regulation
Dan L. Duncan Cancer Center and Center for Reproductive Medicine
Baylor College of Medicine
Houston, TX US
Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
- BCM-Michael DeBakey Center (Office)
Houston, TX 77030
- Lab (Lab)
BCM-Micheal DeBakey Center
Houston, TX 77030
- Post-Doctoral Fellowship at Samsung Biomedical Reserach Institute
- 03/1997 - Seoul, South Korea
- PhD from Seoul National University
- 02/1997 - Seoul, South Korea
- Post-Doctoral Fellowship at Baylor College Of Medicine
- 06/2000 - Houston, Texas United States
- Medical Degree
- Pathogenic Role of Steroid Receptor Coactivator and Nuclear Receptor in Women's Reproductive Disease
Professional StatementAs an estrogen-dependent pro-inflammatory disease, endometriosis is defined as the colonization and growth of endometrial tissues at anatomic sites outside of the uterine cavity, primarily on the pelvic peritoneum and ovaries. Up to 5-10% of reproductive-aged women worldwide chronically suffer from endometriosis symptoms, such as pelvic pain and infertile. Due to the severe chronic morbidity associated with this gynecological disorder, our study has attempted to identify the distinguishing molecular features of endometriotic lesions and endometrial dysfunction to develop more effective prognostic, diagnostic, and/or treatment strategies for the clinical management of this debilitating disease and the amelioration of endometriosis-associated infertility.
Project 1: Estrogen/Estrogen Receptor Beta axis in endometriosis.
Endometriosis is an estrogen-dependent disease. Therefore, the estrogen/Estrogen Receptor (ER)s axis has a critical role in endometriosis progression. Among ERs, the ER-beta level is significantly elevated in endometriotic tissues as compared with normal endometriosis. Now, we will investigate the role of ER-beta in endometriosis progression with the OMICs data set.
Project 2: Dysregulation of Immune in endometriosis
Retrograde menstruation is the main driving factor to initiate the endometriosis progression. To shedding endometrial fragments is developed into endometriotic lesions, the immune system should be dysregulated compared to normal women. However, it is not elucidated how the immune system is changed in endometriosis patients to allow endometriotic lesions. Now, we investigate how endometriotic lesions dysregulate and then generate an endometriosis-competent immune environment to enhance endometriosis.
Project 3: Endocrine disruptor in endometriosis progression
The central hypothesis of endometriosis is retrograde menstruation. Most of the reproductive-aged women (90%) have experienced retrograde menstruation, but 10% of women suffer from endometriosis symptoms. In addition to retrograde menstruation, however, other factors should involve in the initiation of endometriosis. Our hypothesis is the exposure of the environment hormone causes endometriosis progression along with retrograde menstruation. Now, we will investigate the molecular etiology of environmental hormone in endometriosis initiation.
Project 4: Alteration of epigenetic regulation in endometriosis
In addition to genetic variation, the altered epigenomic pattern is also associated with the endometriosis progression. For example, the DNA methylation pattern is quite different between normal endometrium versus endometriotic tissues. Therefore, our project aims to define how DNA methyltransferase involves endometriosis progression with various animal models and human endometriotic lesions.
Project 5: Genetic Mutation Causing Endometriosis
Previous studies revealed exon specific gene mutations are defined in endometriosis patients. However, it is not clearly elucidated whether these genes mutation causes endometriosis progression. Using the CRISPR/Cas9 system, we will determine whether these gene mutations initiate and progress the endometriosis.
Project 6: Diet therapy for the endometriosis
Our studies revealed that ER-beta has an essential role in endometriosis progression. However, most ER-beta antagonists also inhibit ER-alpha activity in vivo and cause side effects by suppressing ER-alpha activity. To effectively suppress endometriosis without side effects, we have screened natural ligands that effectively inhibit ER-beta activity but not ER-alpha activity. Now, we will investigate whether foods that contain high levels of ER-beta inhibiting natural ligands suppress the endometriosis progression.
- Han SJ, O'Malley BW. "The dynamics of nuclear receptors and nuclear receptor coregulators in the pathogenesis of endometriosis." Hum Reprod Update.2014/March14;: Pubmed PMID: 24634322
- Han SJ, O'Malley BW, DeMayo FJ "An estrogen receptor alpha activity indicator model in mice.." Genesis.2009/December;47(12):815-24. Pubmed PMID: 19882671
- Han SJ, Lonard DM, O'Malley BW "Multi-modulation of nuclear receptor coactivators through posttranslational modifications.." Trends Endocrinol. Metab..2009/January;20(1):41501. Pubmed PMID: 19019695
- Han SJ, Jung SY, Malovannaya A, Kim T, Lanz RB, Qin J, O'Malley BW "A scoring system for the follow up study of nuclear receptor coactivator complexes.." Nucl Recept Signal.2006;4:e014. Pubmed PMID: 16862220
- Han SJ, Tsai SY, Tsai MJ, O'Malley BW "Distinct temporal and spatial activities of RU486 on progesterone receptor function in reproductive organs of ovariectomized mice.." Endocrinology. 2007 May ; 148 (5): 2471-86. Pubmed PMID: 17303655
- Liu S, Han SJ, Smith CL "Cooperative activation of gene expression by agonists and antagonists mediated by estrogen receptor heteroligand dimer complexes.." Mol. Pharmacol.. 2013 May ; 83 (5): 1066-77. Pubmed PMID: 23462505
- Han SJ, Jeong J, Demayo FJ, Xu J, Tsai SY, Tsai MJ, O'Malley BW "Dynamic cell type specificity of SRC-1 coactivator in modulating uterine progesterone receptor function in mice.." Mol. Cell. Biol.. 2005 September ; 25 (18): 8150-65. Pubmed PMID: 16135805
- Han SJ, DeMayo FJ, O'Malley BW "Dynamic regulation of progesterone receptor activity in female reproductive tissues.." Ernst Schering Found Symp Proc. 2007 (1): 25-43. Pubmed PMID: 18543433
- Ye X, Han SJ, Tsai SY, DeMayo FJ, Xu J, Tsai MJ, O'Malley BW "Roles of steroid receptor coactivator (SRC)-1 and transcriptional intermediary factor (TIF) 2 in androgen receptor activity in mice.." Proc. Natl. Acad. Sci. U.S.A.. 2005 July 5; 102 (27): 9487-92. Pubmed PMID: 15983373
- Han SJ, DeMayo FJ, Xu J, Tsai SY, Tsai MJ, O'Malley BW "Steroid receptor coactivator (SRC)-1 and SRC-3 differentially modulate tissue-specific activation functions of the progesterone receptor.." Mol. Endocrinol.. 2006 January ; 20 (1): 45-55. Pubmed PMID: 16141356
- Zhang L, Zhang B, Han SJ, Shore AN, Rosen JM, Demayo FJ, Xin L "Targeting CreER(T2) expression to keratin 8-expressing murine simple epithelia using bacterial artificial chromosome transgenesis.." Transgenic Res.. 2012 February 15; : Pubmed PMID: 22350718
- Jeong JW, Lee KY, Han SJ, Aronow BJ, Lydon JP, O'Malley BW, DeMayo FJ "The p160 steroid receptor coactivator 2, SRC-2, regulates murine endometrial function and regulates progesterone-independent and -dependent gene expression.." Endocrinology. 2007 September ; 148 (9): 4238-50. Pubmed PMID: 17556502
- Han SJ, Jung SY , Wu S., Hawkins SM, Park, MJ, Kyo S., Qin J, Lydon JP, Tsai, S.Y., Tsai, M-J., DeMayo FJ, O'Malley BW. "Estrogen Receptor β modulate apoptosis complaex and the inflammasome to drive the pathogensis of endometriosis." Cell. 2015 163 (4): 960-74. Pubmed PMID: 26544941
- Sang Jun Han, Khurshida Begum, Charles E Foulds, Ross A Hamilton, Suzanna Bailey, Anna "The Dual ERα Inhibitory Effects of the Tissue-Selective Estrogen Complex for Endometrial and Breast Safety.." Mol Pharmacol. 2015 October 20; : Pubmed PMID: 26487511
- Han SJ, Hawkins SM, Begum K, Jung SY, Kovanci E, Qin J, Lydon JP, Demayo FJ, O'Malley BW "A new isoform of steroid receptor coactivator-1 is crucial for pathogenic progression of endometriosis.." Nat Med. 2012 June 3; : Pubmed PMID: 22660634
- Yeon Jean Cho, Seung Hyun Lee, Jung Woo Park, Myoungseok Han, Mi Jin Park, Sang Jun Han "Dysfunctional signaling underlying endometriosis: current state of knowledge." J Mol Endocrinol .. 2018 April ; 60 : Pubmed PMID: 29330150
- Cho YJ, Lee JE, Park MJ, O'Malley BW, Han SJ. "Bufalin suppresses endometriosis progression by inducing pyroptosis and apoptosis." J Endocrinol. 2018 June ; 237 : Pubmed PMID: 29636364
- Gilad Y, Eliaz Y, Yu Y, Han SJ, O'Malley BW, Lonard DM. "Drug-induced PD-L1 expression and cell stress response in breast cancer cells can be balanced by drug combination." Sci Rep.. 2019 October ; 9 : Pubmed PMID: 31641154
- Han SJ, Lee JE, Cho YJ, Park MJ, O'Malley BW. "Genomic Function of Estrogen Receptor β in Endometriosis." Endocrinology. 2019 November ; 160 : Pubmed PMID: 31504401
- Mohankumar K, Li X, Sung N, Cho YJ, Han SJ, Safe S. "Bis-Indole-Derived Nuclear Receptor 4A1 (NR4A1, Nur77) Ligands as Inhibitors of Endometriosis." Endocrinology. 2020 April ; 161 : Pubmed PMID: 32099996
- The Genomic Function of Estrogen Receptor Beta in Endometriosis - #R01 HD098059-01A1
- $1,925,830.00 (03/06/2020 - 12/31/2024) Grant funding from NICHD
- The major goals of this project are to define how the specific ER-beta mediated gene network modulate antiapoptosis, epithelial-mesenchymal transition and angiogenesis of endometriotic lesions for the progression of endometriosis.
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