Researchers

  Research Interest  (Regulation of Male Germ Cell Development)

Male germ cell development, spermatogenesis, consists of three steps; proliferation of stem cells by mitosis, production of haploid round spermatids by meiosis, and differentiation of haploid cells to spermatozoa with dramatic morphological and biochemical changes. This is a very complex process regulated by gonadotropin such as leutenizing hormone (LH) and follicle stimulating hormone (FSH), and many local hormones and factors produced in the testis.  LH stimulates the Leydig cells to produce androgen that is absolutely necessary for normal spermatogenesis, and FSH modulates the function of Sertoli cells that physically and biochemically support male germ cells. Our lab are currently taking molecular and developmental genetic approaches to investigate how spermatogenesis is controlled at the molecular and cellular level in mouse system.

1. Regulation of spermatogenesis by testosterone

        Testosterone, a major androgen produced in Leydig cells, is essential for normal spermatogenesis. While there have been numerous studies of endocrine effects of testosterone in spermatogenesis, just beginning are the molecular studies of how the hormone supports male germ cell development.  A number of studies reported so far imply that testosterone indirectly controls spermatogenesis by regulating gene expression and function of supporting cells, Sertoli and Myoid cells in the testis.  Our lab are currently studying how these supporting cells respond to testosterone and how the cells mediate the signal to germ cells to better understand the mechanism by which testosterone controls spermatogenesis.

2. Cloning and functional analysis of genes that regulate spermatogenesis

        Spermatogenesis is an extremely complex process of cellular differentiation that includes the dramatic morphological transformation of haploid spermatids.  This elaborately controlled process is regulated by many hormones and factors involved in cell-cell communications.  Many genes are speculated to be involved in this process and their expressions tightly regulated developmentally by external signals and internal programs in testicular cells.  Our lab has been looking for genes that have a role in the regulation of spermatogenesis and investigating their functions in male germ cell development.
 

  Recent Publications

1. Soma Chattopadhyay, Jin Hee Park, Jae Young Seong, Hyuk Bang Kwon and Keesook Lee (2003) Clonning and Characterization of Androgen Receptor from Bullfrog, Rana catesbeiana. Gen. Comp. Endocrinol. 15;134(1):10-17.
    
2. Hyun Ju Lee, Soma Chattopadhyay, Eun-Yeung Gong, Ryun Sup Ahn and Keesook Lee (2003) Anti-androgenic effects of bisphenol A and nonylphenol on the function of androgen receptor. Toxicol. Sci. 75(1):40-46
    
3. Cheol Yi Hong, Jin Hee Park, Kook Heon Seo, Jin-Man Kim, Suhn Young Im, Jae Woon Lee, Hueng-Sik Choi and Keesook Lee (2003) Expression of MIS in the testis is downregulated by TNF-alpha through the negative regulation of SF-1 transactivation by NF-kappaB. Mol. Cell. Biol. 23(17):6000-6012.
    
4. Sanyal S, Handschin C, Podvinec M, Song KH, Kim HJ, Kim JY, Seo YW, Kim SA, Kwon HB, Lee K, Kim WS, Meyer UA, Choi HS (2003) Molecular cloning and characterization of chicken orphan nuclear receptor cTR2. Gen. Comp. Endocrinol. 132(3):474-84
     
5. Seung-Whan Kim, Keunhee Park, Eunyee Kwak, Eunho Choi, Seunghee Lee, Jungyeob Ham, Heonjoong Kang, Jong Man Kim, Seung Yong Hwang, Young-Yun Kong, Keesook Lee, and Jae Woon Lee  (2003) Activating signal cointegrator 2 required for liver lipid metabolism mediated by liver X receptors in mice. Mol. Cell. Biol. 23:3583-3592
    
6. Hyun Ju Lee, Yong Soo Lee, Hyuk Bang Kwon and Keesook Lee  (2003) Novel yeast bioassay system for detection of androgenic and antiandrogenic compounds. Toxicol. in Vitro 17:237-244
    
7. Lee MY, Jung CH, Lee K, Choi YH, Hong S, Cheong J  (2002) Activating transcription factor-2 mediates transcriptional regulation of gluconeogenic gene PEPCK by retinoic acid.  Diabetes 51:3400-3407
    
8. Yong Soo Lee, Hyun-Jin Kim, Hyun Ju Lee, Jae Woon Lee, Sang-Young Chun, Sun-Kun Ko, and Keesook Lee (2002) Activating Signal Cointegrator 1 Is Highly Expressed in Murine Testicular Leydig Cells and Enhances the Ligand-Dependent Transactivation of Androgen Receptor. Biol Reprod 67: 1580-1587.
    
9. Keesook Lee, Ji-Sun Park, Yun-Jeong Kim, Yong Soo Lee, Tae Sook Hwang, Dae-Joong Kim, Eun-Mi Park and Young-Mee Park (2002) Differential expression of Prx I and Prx II in mouse testis and their up-regulation by radiation.  Biochem. Biophys. Res. Commun. 296, 337-342
    
10. Kwang-Hoon Song, Keesook Lee and Hueng-Sik Choi  (2002) Endocrine disrupter bisphenol A induces orphan nuclear receptor Nur77 gene expression and steroidogenesis in mouse testicular Leydig cells.  Endocrinology 143, 2208-2215
     
11. Kwang-Hoon Song, Jae-Il Park, Mi-Ock Lee, Jaemog Soh, Keesook Lee and Hueng-Sik Choi  (2001) LH induces orphan nuclear receptor Nur77 gene expression in testicular Leydig cells.  Endocrinology 142, 5116-5123
     
12. Joong K. Kim, Sung-Oh Huh, Heonsik Choi, Keesook Lee, Dongho Shin, Changjin Lee, Ju-Suk Nam, Hyun Kim, Heekyoung Chung, Han W. Lee, Sang D. Park, and Rho H. Seong (2001) Srg3, a mouse homolog of yeast SWI3, is essential for early embryogenesis and involved in brain development. Mol Cell Biol 21, 7787-7795
     
13. Jy-Young Park, Jeong-Ho Park, Hyun-Jeong Park, Jy-Young Lee, Yu-Il Lee, Keesook Lee, and Sang-Young Chun  (2001) Stage-dependent regulation of ovarian pituitary adenylate cyclase-activating polypeptide mRNA levels by GnRH in cultured rat granulosa cells.  Endocrnology 142, 3828-3835
     
14. Jae-Il Park, Hyun-jeong Park, Hueng-Sik Choi, Keesook Lee, Won-Kyo Lee, and Sang-Young Chun (2001) Gonadotropin regulation of NGFI-B messenger ribonucleic acid expression during ovarian follicle development in the rat. Endocrinology 142, 3051-3059
     
15. Matthew Smitherman, Keesook Lee, Jherek Swanger, Raj Kapur, Bruce E. Clurman (2000) Characterization and targeted disruption of murine Nup50, a p27kip1-interacting component of the nuclear pore complex. Molecular and Cellular Biology 20, 5631-5642
    
    
16. Maureen C. Ryan, Keesook Lee, Yuko Miyashita and William G. Carter (1999) Targeted disruption of the LAMA3 gene in mice reveals abnormalities in late state differentiation of epithelial cells. J. Cell Biol. 145, 1309-1323
     
17. Jun Zhong, Antoine H. Peters, Keesook Lee, Robert E. Braun (1999) A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells. Nature Genetics, 22, 171-174 
    
    
18. F. William Buaas, Keesook Lee, Susanne Edelhoff, Christine Disteche and Robert E Braun (1999) Cloning and characterization of the mouse Interleukin Enhancer Binding Factor 3 (Ilf3) homolog in a screen for RNA binding proteins. Mammalian Genome 10, 451-456
     
19. Meagher MJ, Schumacher JM, Lee K, Holdcraft RW, Edelhoff S. Disteche C and Braun RE (1999) Identification of ZFR, an ancient and highly conserved murine chromosome-associated zinc finger protein. Gene 228, 197-211
     
20. Keesook Lee, Mark A. Fajardo and Robert E. Braun (1996) A testis cytoplasmic RNA-binding protein that has the the properties of a translational repressor. Molecular and Cellular Biology 16:3023-3034
     
21. Keesook Lee, Harald S. Haugen, Christopher H. Clegg, and Robert E. Braun (1995) Premature translation of protamine 1 mRNA causes precocious nuclear condensation and arrests spermatid differentiation in mice. Proceedings of the National Academy of Sciences USA 92, 12451-12455
     
22. Jill M. Schumacher, Keesook Lee, Susanne Edelhoff and Robert E. Braun (1995) Distribution of Tenr, an RNA binding protein, in a lattice-like network within the spermatid nucleus in the mouse. Biology of Reproduction 52:1274-1283
     
23. Jill M. Schumacher, Keesook Lee, Susanne Edelhoff, and Robert E. Braun (1995) Spnr, a murine RNA binding protein that is localized to cytoplasmic microtubules. The Journal of Cell Biology 129:1023-1032
     
24. Robert E. Braun, Keesook Lee, Jill M. Schumacher and Mark A. Fajardo (1995) Molecular genetic analysis of mammalian spermatid differentiation. Recent Progress in Hormone Research 50:275-286
     
25. Mark A. Fajardo, Karen A. Butner, Keesook Lee, and Robert E. Braun (1994) Germ cell-specific proteins interact with the 3' untranslated regions of Prm-1 and Prm-2 mRNA. Developmental Biology 166:643-653