Ph. D., Principle Investigator
Laboratory of Cancer Resistance
Research Interests or Current Research Focus
Our long term objective is to accelerate the research progress of novel and innovative translational medicine, and develop tumor microenvironment (TME) biology that is based on the state-of-the-art technologies of genomics, transcriptomics, proteomics and secretomics.
The current directions cover but are not limited to:
1) Influence of stressful environmental pressures particularly DNA damage to the expression of secreted proteins generated from stromal cells of solid tumors, and the molecular mechanisms of signal pathway regulation;
2) The pathophysiological consequences of activation of a TME that is activated by the off-target effects of modern anticancer agents (mainly genotoxicities such as chemotherapies and radiation);
3) The impacts of soluble factors derived from the TME on the emergence and stemness maintenance of cancer stem cells (CSCs), and the biological mechanisms of the tumor malignancy and treatment circumvention activities induced by such events;
4) The implication of a physiologically intact immune system in the development of acquired resistance of glandular tumors (prostate tumor, breast tumor, lung tumor, etc) after the patient host has undergone first line chemotherapies, and the underlying mechanisms;
5) Molecular and cellular regulation mechanisms of androgen receptor splicing variants in a subset of prostate cancer patients by transcription factor complexes including NF-kB; the impact of such regulation on intrinsic resistance of advanced tumors particularly CRPC or HRPC.
Major Research Achievement
Advanced expertise and specialized fields are the molecular and cellular biology of stress conditions, the translational medicine between basic and clinical sciences, modern medicine that is based on biological chips (or –omics) and high throughput technologies. We are dedicated and committed to application of frontline theories and research discoveries to disciplines of medicine and pharmacology thereby effectively minimizing the distance from basic research to clinics (therapeutic intervention).
After the Ph.D. stage, Dr. Sun experienced systemic training and performed productive research in the ovarian and prostate cancer research fields. He found the transcription factor, ZNF217 (a Krüppel-like zinc-finger protein) can drive primary ovarian surface epithelial cells through crisis and toward transformation. Further, via CGH-based whole genome analysis he found majority of the cellular features controlled by ZNF217 are eventually mediated by the eukaryotic translational initiation factor EEF1A2. Correspondingly, he raised a hypothesis that the sporadic and inheritable variances of ovarian-specific amplification of chromosome fragment 20q12-q13 including ZNF217, are indeed altering neoplastic cells through the protein translational levels.
In the area of prostate cancer (PCa) research, which became the 2nd expertise, Dr. Sun constructed a series of transgenic mouse models that overexpresses TMPRSS2 in an organ-specific manner, and found that this serine protease leads to comprehensive metastasis to multiple organs after crossed to the PCa primary model LADY. This was considered a major milestone in PCa research, particularly in the metastasis branch. Dr. Sun was press interviewed by US military media in a special session of DoD IMPACT conference 2011 (Orlando, FL), and relevant AVs were deposited into the Medical Library of US Army. This work is still ongoing in the Seattle lab, under Dr. Nelson’s supervision.
More importantly, Dr. Sun discovered the off-target effects of DNA damaging genotoxic treatments (chemotherapies and radiation) in activation of the tumor microenvironment (TME), which is proved to play an indispensable role in conferring migration, invasiveness, metastasis and resistance capabilities of cancer. Together with US Berkeley collaborators, he found that DNA damage can induce a special cell secretion phenotype, namely DNA damage secretory program (DDSP).He emphasizes that DDSP is highly complicated and robust, as an evolutionally reserved response of mammalian cells to genotoxicity. As a pilot scientist, he first proposed that TME can allow cancer cells to gain acquired resistance, through a continuous, chronic and slow process, which is essentially cell non-autonomous. Importantly, he established a complete set of treatment technique and intervention strategy for experimental mice, as a most effective approach to mimic and recapitulate the dynamics of TME under chemo-conditions. This contribution has been filed as a patent in US, which provides a novel preclinical model for tumor biology. As a cornerstone of mainstay anticancer treatments particularly chemo and radiation therapies, he opened a new avenue for modern medicine, and this is considered to be a major breakthrough in the light of advanced translational research.
1992-1996: Yantai University, Biochemistry and Microbiology Department, B.S.
1996-1999: Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, M.S.
2000-2005: Dalhousie University (Canada), Ph.D.
- Sun, Y., Zhu, D., Chen, F., Qian, M., Wei, H., Chen, W. and Xu, J. 2015. SFRP2 augments WNT16B signaling to promote therapeutic resistance in the damaged tumor microenvironment. Oncogene. doi: 10.1038/onc.2015.494 (Epub ahead of print)
- Zhang, B. and Sun, Y. Landscape and Targeting of the Angpt-Tie System in Current Anticancer Therapy. Translational Med. 5: 157.
- Sun, Y. 2015. Tumor Microenvironment and Cancer Therapy Resistance. Cancer Lett. pii: S0304-3835(15)00512-1.
- Laberge, R. M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., Limbad, C., Demaria, M., Li, P., Hubbard, G. B., Ikeno, Y., Javors, M., Desprez, P. Y., Benz, C. C., Kapahi, P., Nelson, P. S. and Campisi, J. 2015. mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nat. Cell. Biol. 17: 1049-1061.
- Chen, F., Zhuang, X., Lin, L., Yu, P., Wang, Y., Shi, Y., Hu G. and Sun, Y. 2015. New Horizons in the Tumor Microenvironment Biology: Challenges and Opportunities. BMC Medicine. 13: 45.
- Sun, Y. 2015. Translational Horizons in the Tumor Microenvironment: Harnessing Breakthroughs and Targeting Cures. Med. Res. Rev. 35: 408-436.
- Chen, F., Qi, X., Qian, M., Dai, Y. and Sun, Y. 2014. Tackling the Tumor Microenvironment: What Challenge Does It Pose to Anticancer Therapies? Protein Cell. 5: 816-826.
- Sun, Y., Campisi, J., Higano, C., Beer, T. M., Porter, P., Coleman, I., True, L. and Nelson, P. S. 2012. Treatment-Induced Damage to the Tumor Microenvironment Promotes Prostate Cancer Therapy Resistance through WNT16B. Nat. Med. 18: 1359-1368. (Article featured by the journal, reviewed by , Cancer Discovery, Nature, Nature Medicine, and Nature Reviews Clinical Oncology).
- Sun, Y. and Nelson, P. S. 2012. Molecular Pathways: Involving Microenvironment Damage Responses in Cancer Therapy Resistance. Clin Cancer Res. 18: 4019-4025.
- Bluemn, E. G., Paulson, K. G., Higgins, E. E., Sun, Y., Nghiem, P. and Nelson, P. S. 2009. Merkel Cell Polyomavirus is not Detected in Prostate Cancers, Surrounding Stroma, or Benign Prostate Controls. J Clinical Virology. 44: 164-166.
- Coppé, J. -P., Patil, C. K., Rodier, F., Sun, Y., Muñoz, D. P., Goldstein, J, Nelson, P. S., Desprez, P. –Y., and Campisi, J. 2008. Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor. PloS Biology. 6: 2853-2868.
- Sun, Y., Wong, N., Guan, Y., Salamanca, C. M., Cheng, J. C., Lee, J. M., Gray, J. W., and Auersperg, N. 2008. The Eukaryotic Translation Elongation Factor eEF1A2 Induces Neoplastic Properties and Mediates Tumorigenic Effects of ZNF217 in Precursor Cells of Human Ovarian Carcinomas. Int J Cancer. 123: 1761-1769.
- Li, P., Maines-Bandiera, S., Kuo, W., Guan, Y., Sun, Y., Hills, M., Huang, G., Collins, C. C., Leung, P. C. K., Gray, J. W. and Auersperg, N. 2007. Multiple Roles of the Candidate Oncogene ZNF217 in Ovarian Epithelial Neoplastic Progression. Int J Cancer. 120:1863-1873.
- Sun, Y., Bojikova-Fournier, S. and MacRae, T. H. 2006. Structural and Functional Roles for β-Strand 7 in the α-Crystallin Domain of p26, a Poly-disperse Small Heat Shock Protein from the Extremophile, Artemia franciscana. FEBS J. 273: 1020-1034.
- Villeneuve, T. S., Ma, X., Sun, Y., Oulton, M. M., Oliver, A. E. and MacRae, T. H. 2006. Inhibition of Apoptosis by p26: Implications for Small Heat Shock Protein Function during Artemia Development. Cell Stress & Chaperones. 11: 71-80.
- Ma, X., Jamil, K., MacRae, T. H., Clegg, J. S, Russell, J. M., Villeneuve, T. S., Euloth, M., Sun, Y., Crowe, J. H., Tablin, F. and Oliver, A. E. 2005. A Small Stress Protein Acts Synergistically with Trehalose to Confer Desiccation Tolerance on Mammalian Cells. Cryobiology. 51: 15-28.
- Sun, Y. and MacRae, T. H. 2005. Characterization of Novel Sequence Motifs within Amino- and Carboxy-Terminal Extensions of p26, a Small Heat Shock Protein from Artemia franciscana. FEBS J. 272: 5230-5243.
- Sun, Y. and MacRae, T. H. 2005. Small Heat Shock Proteins: Molecular Structure and Chaperone Function. Cell Mol. Life Sci. 62: 2460-2476.
- Sun, Y. and MacRae, T. H. 2005. The Small Heat Shock Proteins and their Role in Human Disease. FEBS J. 272: 2613-2627.
- Sun, Y., Mansour, M., Crack, J. A., Gass, G. L. and MacRae, T. H. 2004. Oligomerization, Chaperone Activity and Nuclear Localization of p26, a Small Heat Shock Protein from Artemia franciscana. J. Biol. Chem. 279: 39999-40006.
- Crack, J., Mansour, M., Sun, Y. and MacRae, T. H. 2002. Functional Analysis of a Small Heat Shock/alpha-Crystallin Protein from Artemia franciscana. Eur. J. Biochem. 269: 933-942.
- Chen, J., Fu, H., Que, Q., Lu, Z., Song, L. and Sun, Y. 1998. Effects of HSP70 Gene Expression on the Fertility of Sorghum. Dev. and Rep. Biol. 13: 51-62.
- Chen, J., Wang, L., Sun, Y., Qi, X. and Liu, G. 1999. Regulatory Mechanism of Sorghum to Realize Cytoplasmic Male Sterility (CMS) through Controlling Mitochondria Amounts by HSP70 (Supplement of 6th Congress of Genetics, China). J. Yunnan Uni. (Natural Sciences). 21: 63-67.