Transcriptional control is a key step in the regulation of eukaryotic gene expression. Our research group is focusing on understanding the molecular mechanism of transcription factors that govern the transformation of normal mammalian cells to a neoplastic state. We are especially interested in the biological roles of steroid hormone receptors and their coregulators in development and oncogenesis. We use targeted conditional and inducible mouse models and other cellular and molecular approaches to uncover gene expression and genomic and epigenetic alteration during tumor development and progression. In recent years, we have demonstrated crutical roles and underlying mechanisms for androgen signaling in interacting with Wnt, Sonic hedgehog, IGF, HGF, and other signaling pathways to regulate prostate development and tumorigenesis. Ongoing projects in the lab are investigating several novel and important questions regarding stromal androgen action as tumor niches in supporting prostate cancer growth and progression, and the molecular mechanisms underlying current androgen deprivation therapy (ADT) induced castration resistant prostate cancer (CRPC) development. Our foremost scientific goal is to translate our scientific discoveries from bench to bedside to improve clinical outcomes and help prostate cancer patients. 

(Most recent publications)

Kim WK, Buckley AJ, Lee DH, Hiroto A, Nenninger CH, Olson AW, Wang J, Adzavon YM, Bao Y, Kahn M, Xiao GQ, Geradts J, Sun ZJ (2024). Androgen Deprivation Induces Double-Null Prostate Cancer via Aberrant Activating Nuclear Exporting and Ribosomal Biogenesis by HGF and Wnt Axes. Nat Communs 15(1):1231. PMID: 383363745

Kim J, Freeman K, Ayala A, Mullen M, Sun ZJ, Rhee JW (2023). Cardiovascular impact of androgen deprivation therapy: from basic biology to clinical practice. Current Oncol Rep. doi: 10.1007/s11912-023-01424-2. PMID: 37273124 

Alghamdi TA, Krentz NAJ, Smith N, Spigelman AF, Rajesh V, Jha A, Ferdaoussi M, Suzuki K, Yang J, Manning Fox JE, Sun H, Sun ZJ, Gloyn AL, MacDonald PE (2022). Zmiz1 is required for mature β-cell function and mass expansion upon high fat feeding. Mol Metab. 2022 Dec;66:101621. doi: 10.1016/j.molmet.2022.101621. Epub 2022 Oct 26.PMID: 36307047 

Hiroto A, Kim WK, Pineda A, He Y, Lee DH, Le V, Olson AW, Aldahl J, Nenninger CH, Buckley AJ, Xiao GQ, Geradts J, Sun ZJ (2022). Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis. Nat Communs. 13(1):6552. PMID: 36323713

Kim WK, Olson AW, Le V, Mi J, Wang J, Lee DH, Le V, Hiroto A, Aldahl J, Nenninger CH, Buckley AJ, Cardiff RD, You SY, Sun ZJ. (2022). Aberrant androgen action in prostatic progenitor cells induces oncogenesis and tumor development through IGF1 and Wnt axes. Nat Communs, 28;13 (1) :4364. PMID:35902588, PMCID: PMC9334353

Olson AW, Le V, Wang J, Hiroto A, Kim WK, Lee DH, Aldahl J, Wu X, Kim M, Cunha GR, You S, Sun ZJ (2021). Stromal androgen and hedgehog signaling regulates stem cell niches in pubertal prostate development. Development. PMID: 34427305 

Lee DH, Olson AW, Wang J, Kim WK, Mi J, Zeng H, Le V, Aldahl J, Hiroto A, Wu X, Sun ZJ (2021). Androgen action in cell fate and communication during prostate development at single-cell resolution. Development. doi: 10.1242/dev.196048. PMID: 33318148

He Y, Mi J, Olson A, Aldahl J, Hooker E, Yu EJ, Le V, Lee DH, Kim WK, Robins DM, Geradts J, Sun ZJ (2020). Androgen receptor with short polyglutamine tract preferably enhances Wnt/ß-catenin-mediated prostatic tumorigenesis. Oncogene. 39(16):3276-3291.PMID: 32089544

Le V, He Y, Aldahl J, Hooker E, Yu EJ, Olson A, Kim WK, Lee DH, Wong M, Sheng R, Mi J, Geradts J, Cunha GR, Sun ZJ (2020). Loss of androgen signaling in mesenchymal sonic hedgehog responsive cells diminishes prostate development, growth, and regeneration. PLoS Genet. 16(1):e1008588. PMID: 31929563, PMCID: PMC6980684

Aldahl J, Mi J, Pineda A, Kim WK, Olson A, Hooker E, He Y, Yu EJ, Le V, Lee DH, Geradts J, Sun ZJ (2020). Aberrant activation of hepatocyte growth factor/MET signaling promotes ß-catenin-mediated prostatic tumorigenesis. J Biol Chem. 295(2):631-644. doi: 10.1074/jbc.RA119.011137. PMID: 31819003

He YF, Hooker E, Yu EJ, Wu H, Xu JM, Cunha GR, Sun ZJ (2019). Androgen signaling is essential for development of prostate cancer initiated from prostatic basal cells. Oncogene. 38(13):2337-2350. doi: 10.1038/s41388-018-0583-7. PMID: 30510232

He YF, Johnson DT, Yang JS, Wu H, You S, Yoon J, Lee DH, Kim WK, Aldahl J, Le V, Hooker E, Yu EJ, Geradts J, Cardiff RD, Sun ZJ (2019). Loss of the tumor suppressor, Tp53, enhances the androgen receptor-mediated oncogenic transformation and tumor development in the mouse prostate. Oncogene. 38(38):6507-20. doi: 10.1038/s41388-019-0901-8. Epub 2019 Jul 29.  PMID: 31358900

Olson A, Le V, Aldahl J, Yu EJ, Hooker E, He Y, Lee DH, Kim WK, Cardiff RD, Geradts J, Sun ZJ (2019).  The comprehensive role of E-cadherin in maintaining prostatic epithelial integrity during oncogenic transformation and tumor progression. PLoS Genet. 15(10):e1008451. doi: 10.1371/journal.pgen.1008451. PMID: 31658259, 

Aldahl J, Yu EJ, He YF, Hooker E, Wong M, Le V, Olson A, Lee DH, Kim WK, Murtaugh CL, Cunha GR, Sun ZJ (2019).  A pivotal role of androgen signaling in notch-responsive cells in prostate development, maturation, and regeneration.  Differentiation, 2019 May-Jun;107:1-10. PMID: 309276418. 

He YF, Hooker E, Yu EJ, Wu H, Cunha GR, Sun ZJ (2018). An indispensable role of androgen receptor in Wnt responsive cells during prostate development, maturation, and regeneration. Stem Cells. Jun; 36(6):891-902. doi: 10.1002/stem.2806. PMID: 29451339

Mi J, Hooker E, Balog S, Zeng H, Johnson DT, He YF, Yu EJ, Wu H, Le V, Lee DH, Aldahl J, Gonzalgo M, Sun ZJ (2018). Activation of hepatocyte growth factor/MET signaling initiates oncogenic transformation and enhances tumor progression in the murine prostate. J Biol Chem. 293(52):20123-20136. PMID: 30401749