Department of Molecular Medicine
 

Rong Li Rong  LiPh.D.

Professor


Profile and Contact Information | Research | Laboratory


RESEARCH

 

Research Program

Our laboratory addresses the following three fundamental questions concerning breast cancer treatment and prevention.

1. How does BRCA1 suppress tumor development in a gender- and tissue-specific manner?
Women who carry cancer-predisposing germ-line mutations in BRCA1 have significantly increased chance of developing breast and ovarian cancers. While the BRCA1 activity in DNA repair is clearly important to the etiology of BRCA1-associated cancers, it is not clear whether the DNA repair function alone is sufficient to account for the gender- and tissue-specific tumor suppression by BRCA1. We previously identified a BRCA1-binding protein COBRA1, which is identical to the B subunit of NELF involved in pausing of RNA polymerase II. Using mouse genetics and clinical samples from BRCA1 mutation carriers, we are investigating whether a crosstalk between BRCA1 and COBRA1-regulated transcription machinery contributes to the tissue-specific function of BRCA1 in breast epithelium.

2. How can the antitumor activity of estrogen receptor β(ER β) be mobilized?
In contrast to the tumor-promoting activity of ERβ, ERβ inhibits tumor growth in breast cancer. Because ERβ is present in a significant percentage of breast cancer cases, rallying its antitumor activity could serve as a potential therapeutic approach. Our pioneer discovery of a phosphotyrosine switch for the antitumor activity of ERβ enables us to mobilize ERβ function with unprecedented precision. We are testing the hypothesis that turning on this molecular switch of ERβ can inhibit triple negative breast cancer and circumvent hormonal resistance of ERβ-positive breast cancer, two clinically pressing areas where therapeutic potential of ERβ has been previously demonstrated.

3. How do adipose stromal cells (ASC) promote breast cancer progression?
ASC is a major constituent of the breast and a source of tumor-promoting factors including estrogens. We recently discovered a new mechano-transducing pathway that links mechanical phenotype with the endocrine/paracrine output of ASCs. This pathway is initiated by a cell surface receptor called discoidin domain receptor 1 (DDR1). Combining three-dimension cell culture systems and animal models, we are exploring novel therapeutic approaches to disrupt this stroma-tumor communication.

 

Selected Publications

  1. Yuan B, Cheng L, Chiang H-C, Xu X, Han Y, Su H, Wang L, Zhang B, Li J, Tekmal J, Li X, Xie X, Wang T, Tekmal RR, Curiel TJ, Yuan Z-Y, Elledge R, Hu Y, Ye Q, Li R. (2014) A phosphotyrosine switch determines the antitumor activity of ERβ. J. Clin. Invest. 124:3378.
  2. Pan H, Qin K, Guo Z, Ma Y, April C, Gao X, Andrews TG, Bokov A, Zhang J, Chen Y, Weintraub ST, Fan J-B, Wang D, Hu Y, Aune GJ, Lindsey ML, Li R. (2014) Negative elongation factor controls energy homeostasis in cardiomyocytes. Cell Rep, 7:79.
  3. Hsu P-Y, Hsu H-K, Lan X, Juan L, Yan PS, Labanowska J, Heerema N, Hsiao T-H, Chiu Y-C, Chen Y, Liu Y, Li L, Li R, Thompson IM, Nephew KP, Sharp ZD, Kirma NB, Jin VX, Huang T H-M. (2013) Amplification of distant estrogen response elements deregulates target genes associated with tamoxifen resistance in breast cancer. ,Cancer Cell 24:197.
  4. Ghosh S, Ashcraft K, Jahid MJ, April C, Ghajar CM, Ruan J, Wang H, Foster M, Hughes DC, Ramirez AG, Huang T, Fan JB, Hu Y, and Li R. (2013) Regulation of adipose oestrogen output by mechanical stress. Nat Commun. 4: 1821.
  5. Sun J, Pan H, Lei C, Yuan B, Nair SJ, April C, Parameswaran B, Klotzle B, Fan JB, Ruan J, and Li R. (2011) Genetic and genomic analyses of an RNA polymerase II-pausing factor in regulation of mammalian transcription and cell growth. J Biol Chem. 286(42): 36248-57.
  6. Sun J and Li R. (2010) Human negative elongation factor activates transcription and regulates alternative transcription initiation. J Biol Chem. 285(9): 6443-52.
  7. Walter M, Liang S, Ghosh S, Hornsby PJ, and Li R. (2009) Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene. 28(30): 2745-55.
  8. Ghosh S, Choudary A, Ghosh S, Musi N, Hu Y, and Li R. (2009) IKK{beta} mediates cell shape-induced aromatase expression and estrogen biosynthesis in adipose stromal cells. Mol Endocrinol. 23(5): 662-70.
  9. Aiyar SE, Blair AL, Hopkinson DA, Bekiranov S, and Li R. (2007) Regulation of clustered gene expression by cofactor of BRCA1 (COBRA1) in breast cancer cells. Oncogene. 26(18): 2543-53.
  10. Hu Y, Ghosh S, Amleh A, Yue W, Lu Y, Katz A, and Li R. (2005) Modulation of aromatase expression by BRCA1: a possible link to tissue-specific tumor suppression. Oncogene. 24(56): 8343-8.
  11. Aiyar SE, Sun JL, Blair AL, Moskaluk CA, Lu YZ, Ye QN, Yamaguchi Y, Mukherjee A, Ren DM, Handa H, and Li R. (2004) Attenuation of estrogen receptor alpha-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor. Genes Dev. 18(17): 2134-46.
  12. Hu YF and Li R. (2002) JunB potentiates function of BRCA1 activation domain 1(AD1) through a coiled-coil-mediated interaction. Genes Dev. 16(12): 1509-17.
  13. Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, and Li R. (2001) BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations. J Cell Biol. 155(6): 911-21.
  14. Hu YF, Hao ZL, and Li R. (1999) Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1. Genes Dev. 13(6): 637-42.