Department of Molecular Medicine

HuY.jpg Yanfen  HuPh.D.

Associate Professor

Profile and Contact Information | Research | Laboratory



Research Program

Breast cancer is the most common malignancy among women in the Western world. Between 5 to 10% of breast cancer cases are hereditary, the majority of which are caused by germline mutations in the breast cancer susceptibility gene BRCA1 or BRCA2. In addition, germline mutations in these two genes also lead to increased risk of hereditary ovarian cancer. The long-term objective of my research is to elucidate the underlying mechanism by which BRCA1 suppresses development of breast and ovarian cancers in women.

BRCA1 has been mainly implicated in two cellular functions: DNA repair and transcriptional regulation. The function of BRCA1 in DNA damage response provides a reasonable molecular explanation for its role as a tumor suppressor, but the exact role of BRCA1 in DNA repair remains elusive. In addition, DNA repair function is not sufficient to address two conundrums regarding BRCA1 functions: 1) Why do mutations in BRCA1 specifically lead to breast and ovarian cancer in women (gender- and tissue-specificity)? 2) Why are somatic mutations of BRCA1 rarely found in sporadic breast cancers?

We have launched studies in both tissue culture and animal models in the following two directions:

I. Role of BRCA in DNA double-strand breaks repair: The ongoing research in my laboratory has been focusing on the function of BRCA1 phosphorylation in DNA double-strand break repair and maintaining genome stability (mechanism of tumor suppression).

II. Role of BRCA1 in Estrogen Biosynthesis: We are testing the hypothesis that BRCA1 might down-regulate the estrogen biosynthesis by negatively regulating the expression of aromatase, the rate-limiting enzyme in estrogen biosynthesis. The expression of aromatase and hence the production of estrogen is highly tissue specific. Importantly, estrogen plays a significant role in the development and progression of breast cancer, and aromatase is a clinically proven target for breast cancer treatment (potential mechanism of tissue-, gender-specificity).


Selected Publications

  1. Zhang X, Chiang H-C, Wang Y, Zhang C, Smith S, Zhao X, Nair S, Michalek J, Jatoi J, Lautner M, Oliver B, Wang H, Petit A, Soler T, Brunet J, Mateo F, Pujana MA, Poggi E, Chaldekas K, Isaacs C, Peshkin BN, Ochoa O, Chedin F, Theoharis C, Sun L-Z, Curiel TJ, Elledge R, Jin VX*, Hu, Y*, Li R*. (2017) Attenuation of RNA Polymerase II Pausing Mitigates BRCA1-Associated R-loop Accumulation and Tumorigenesis. Nat Commun. In press. (*co-corresponding authors).

  2. Nair S, Zhang X, Chiang H-C, Jahid MJ, Wang Y, Garza P, April C, Salathia N, Banerjee T, Gelfond JAL, Alenazi FS, Ruan J, Fan J-B, Parvin JD, Jin VX, Hu Y, Li R. (2016) Genetic Suppression Reveals DNA Repair-Independent Antagonism between BRCA1 and COBRA1 in Mammary Gland Development. Nat Commun. In press.

  3. Chiang HC, Elledge R, Larson P, Jatoi I, Li R, and Hu Y. (2015) Effects of Radiation Therapy on Breast Epithelial Cells in BRCA1/2 Mutation Carriers. Breast Cancer: Basic and Clinical Research 9:25-29. PMID: 26052229

  4. Pan H, Zhao X, Zhang X, Abouelsoud M, Sun J, April C, Amleh A, Fan JB, Hu Y, Li R. (2015) Translational Initiation at a Non-AUG Start Codon for Human and Mouse Negative Elongation Factor-B. PloS one. 10(5):e0127422. PMID:26010750

  5. Pan H, Qin K, Guo Z, Ma Y, April C, Gao X, Andrews TG, Bokov A, Zhang J, Chen Y, Weintraub ST, Fan JB, Wang D, Hu Y, Aune GJ, Lindsey ML, Li R. (2014) Negative elongation factor controls energy homeostasis in cardiomyocytes. Cell Rep. 7(1):79-85.PMID:24656816

  6. Yuan B, Cheng L, Chiang HC, Xu X, Han Y, Su H, Wang L, Zhang B, Lin J, Li X, Xie X, Wang T, Tekmal RR, Curiel TJ, Yuan ZM, Elledge R, Hu Y, Ye Q, Li R. (2014) A phosphotyrosine switch determines the antitumor activity of ERÉ¿. The Journal of Clinical Investigation. 124(8):3378-90. PMID: 24960160

  7. Ghosh S, Gu F, Wang CM, Lin CL, Liu J, Wang H, Ravdin P, Hu Y, Huang TH, Li R. (2014) Genome-wide DNA methylation profiling reveals parity-associated hypermethylation of FOXA1. Breast Cancer Research and Treatment. 147(3):653-9. PMID: 25234841

  8. Balaji Parameswaran, Huai-Chin Chiang, Yunzhe Lu, Julia Coates, Chu-Xia Deng, Richard Baer, Hui-Kuan Lin, Rong Li, Tanya T. Paull & Yanfen Hu (2015). Damage-induced BRCA1 phosphorylation by Chk2 contributes to the timing of end resection Cell Cycle 14(3):437-448.

  9. 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.

  10. Lu Y, Li J, Cheng D, Parameswaran B, Zhang S, Jiang Z, Yew PR, Peng J, Ye Q, and Hu Y: (2012) The F-box protein FBX044 mediates BRCA1 ubiquitination and degradation. J Biol Chem. 287(49): 41014-22.

  11. Chiang HC, Nair SJ, Yeh IT, Santillan AA, Hu Y, Elledge R, and Li R: (2012) Assocation of radiotherapy with preferential depletion of luminal epithelial cells in a BRCA1 mutation carrier. Exp Hematol Oncol. 1(1): 31.

  12. Ghosh S, Kang T, Wang H, Hu Y, and Li R: (2011) Mechanical phenotype is important for stromal aromatase expression. Steroids. 76(8): 797-801.

  13. Lu Y, Kang T, and Hu Y: (2011) BRCA1/BARD1 complex interacts with steroidogenic factor 1- A potential mechanism for regulation of aromatase expression by BRCA1. J Steroid Biochem Mol Biol. 123(1-2): 71-8.

  14. Ghosh S, Dean A, Walter M, Bao Y, Hu Y Ruan J, and Li R: (2010) Cell density-dependent transcriptional activation of endocrine-related genes in human adipose tissue-derived stem cells. Exp Cell Res. 316(13): 2087-98.

  15. Ghosh S, Hu Y, and LI R: (2010) Cell density is a critical determinant of aromatase expression in adipose stromal cells. J Steroid Biochem Mol Biol. 118: 231-6.

  16. Wang H, Li R, and Hu Y: (2009) The alternative noncoding exons 1 of aromatase (cyp19)gene modulate gene expression in a posttranscriptional manner. Endocrinology. 150(7): 3301-7.

  17. 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.

  18. Hu Y: (2009) BRCA1, hormone, and tissue-specific tumor suppression. (Review) Int J Biol Sci. 5(1): 20-7.

  19. Ghosh S, Lu Y, and Hu Y: (2008) A Role of CREB in BRCA1 Constitutive Promoter Activity and Aromatase Basal Expression. Intl J Biomedical Sci. 4(4): 260-5.

  20. Lu Y, Amleh A, Sun J, Jin X, McCullough SD, Baer R, Ren D, Li R, and Hu Y: (2007) Ubiquitination and proteasome-mediated degradation of BRCA1 and BARD1 during steroidogenesis in human ovarian granulosa cells. Mol Endocrinol. 21(3): 651-63.

  21. Hu Y*, Ghosh S, Amleh A, Yue W, Lu Y, Katz A, and Li R* (*co-corresponding authors): (2005) Modulation of aromatase expression by BRCA1: a possible link to tissue-specific tumor suppression. Oncogene. 24(56): 8343-8.

  22. Wu Y, Lu Y, Hu Y, and Li R: (2005) Cyclic AMP-dependent modification of gonad-selective TAF(II)105 in a human ovarian granulosa cell line. J Cell Biochem. 96(4): 751-9.

  23. Ghosh S, Wu Y, Li R, and Hu Y: (2005) Jun proteins modulate the ovary-specific promoter of aromatase gene in ovarian granulosa cells via a cAMP-responsive element. Oncogene. 24(13): 2236-46.

  24. Wu Y, Ghosh S, Nishi Y, Yanase T, Nawata H, and Hu Y: (2005) The orphan nuclear receptors NURR1 and NGFI-B modulate aromatase gene expression in ovarian granulosa cells: a possible mechanism for repression of aromatase expression upon luteinizing hormone surge. Endocrinology. 146(1): 237-46.

  25. 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.

  26. 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.

  27. Hu Y, Miyake T, Ye Q, Li R: (2000) Characterization of a novel trans-activation domain of BRCA1 that functions in concert with the BRCA1 C-terminal (BRCT) domain. J Biol Chem. 275(52): 40910-5.

  28. Miyake T, Hu YF, Yu DS, and Li R: (2000) A functional comparison of BRCA1 C-terminal domains in transcription activation and chromatin remodeling. J Biol Chem. 275(51): 40169-73.

  29. 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.