Zhe Yang
Education
Ph.D. Institute of Biophysics, Chinese Academy of Sciences, Beijing, P. R. China, 1999
Postdoctoral:
Emory University, Atlanta, GA, 2007
University of California at San Diego, La Jolla, CA, 2002
Graduate
Accepting new MS students in 2023: Yes (BMB)
Accepting new PhD students in 2023: Yes (BMB)
Office Location
4340 Scott Hall
Research
Structure and function of SET and MYND domain-containing (SMYD) proteins.
Research Focus
Our research focuses on the SMYD protein family, a special class of protein lysine methyltransferases whose origins can be traced back an astonishing 1.5 billion years ago to the beginning of eukaryotic life. The emergence of this family, resulting from the insertion of an MYND domain into a SET domain, marks a pivotal event in evolutionary history owing to their profound biological importance. SMYD proteins play crucial roles in early cardiac development and maintain the delicate balance of stem cell self-renewal and differentiation. Dysregulation of SMYD proteins is linked to cardiovascular disease, inflammatory disorders, and various cancers. Our research addresses pressing issues in their structure and function, offering exciting prospects for the development of novel cancer therapeutics.
We have made significant advances in elucidating the structure and function of SMYD proteins using X-ray crystallography. Our pioneering work has yielded groundbreaking insights into the substrate specificity and promiscuity of these proteins. Leveraging this knowledge, we are developing novel cancer therapeutics targeting SMYD proteins. Our multidisciplinary approach, combining structural biology, computational modeling, and biochemical and cellular assays, holds great promise for identifying new drug candidates with improved efficacy and specificity. We are expanding our research to include the structural characterization of additional SMYD protein family members, such as SMYD4 and SMYD5. By unraveling the structures of these proteins, we aim to discover novel therapeutic targets for diseases like Miller-Dieker syndrome and gain deeper insights into the molecular mechanisms driving cancer progression.
We are also keen on investigating the commonalities shared among various cancer types. Our overarching goal is to identify the shared cellular processes that underlie the development of a broad spectrum of cancers. By doing so, we aim to develop robust strategies that can target multiple cancer types simultaneously. We are exploring a novel hypothesis in pan-cancer, where SMYD proteins function as RNA chaperones in coordinating the two fundamental cellular processes: nucleolar RNA processing and mitochondrial ribosome synthesis. In this hypothesis, we seek to uncover the novel mechanisms by which cancer cells adapt to changing nutrient environments and determine the crucial role of SMYD proteins within them. We utilize a multidisciplinary approach integrating bioinformatics, cell biology, and molecular genetics to achieve this important goal. This study could offer novel insights into cancer cell survival mechanisms, paving the way for broad-spectrum treatments for a larger population of patients.
We are also interested in the intricate mechanisms underlying spermatogenesis. We are studying how SMYD proteins regulate the spermatogenic process through modulating secondary structures of specific RNA molecules. This pioneering research will not only deepen our understanding of core cellular processes in spermatogenesis but also holds significant implications for addressing male infertility, a pressing global health concern. Specifically, we are investigating how the balance between self-renewal and differentiation in sperm stem cells is controlled by SMYD5, and the impact of abnormal SMYD5 activity on male fertility. Leveraging this deep understanding of SMYD5 biology, we aim to pioneer the development of targeted therapeutics to restore normal spermatogenesis in infertile individuals. These promising approaches hold the potential to revolutionize fertility treatment strategies.
Publications
1. Shen, J., Ju, D., Wu, S., Zhao, J., Pham, L., Ponce, A., Yang, M., Li, H., Zhang, K., Yang, Z., Xie., Y., Li, L. SM22α deficiency: promoting vascular fibrosis via SRF-SMAD3-mediated activation of Col1a2 transcription following arterial injury. https://doi.org/10.21203/rs.3.rs-3941602/v1 (2024).
2. Zhou, Y., Sharma, S., Sun, X., Guan, X., Hou, Y., Yang, Z., Zou, M., Song, P., Zhou, J., Wang, S., Hu, Z., Li, C. SMYD2 Regulates Vascular Smooth Muscle Cell Phenotypic Switching and Intimal Hyperplasia via Interaction with Myocardin. Cellular and Molecular Life Sciences, 80(9):264, https://doi.org/10.1007/s00018-023-04883-9 (2023).
3. Yang, A., Zhang, Y. and Yang, Z. Artificial intelligence and machine learning of single-cell transcriptomics of engineered nanoparticles. Impact of Engineered Nanomaterials in Genomics and Epigenomics, https://doi.org/10.1002/9781119896258.ch12, Wiley (2023).
4. Zhang, Y., Alshammari, E., Yonis, N. and Yang, Z. Adverse epigenetic effects of environmental engineered nanoparticles as drug carriers. Impact of Engineered Nanomaterials in Genomics and Epigenomics, https://doi.org/10.1002/9781119896258.ch10, Wiley (2023).
5. Alshammari, E., Zhang, Y., Yang, A. and Yang, Z. Toxicogenomics and toxicological mechanisms of engineered nanomaterials. Impact of Engineered Nanomaterials in Genomics and Epigenomics, https://doi.org/10.1002/9781119896258.ch13, Wiley (2023).
6. Zhang, Y., Yang, A. and Yang, Z. Engineered nanoparticles adversely impact glucose energy metabolism. Impact of Engineered Nanomaterials in Genomics and Epigenomics, https://doi.org/10.1002/9781119896258.ch11, Wiley (2023).
7. Yonis, N, Alshammari, E., Zhang, Y. and Yang, Z. Carbon nanotubes alter metabolomics pathways leading to toxicity. Impact of Engineered Nanomaterials in Genomics and Epigenomics, https://doi.org/10.1002/9781119896258.ch14, Wiley (2023).
8. Zhang, Y., Alshammari, E., Sobota, J., Yang, A., Li, C. and Yang, Z. Unique SMYD5 Structure Revealed by AlphaFold Correlates with Its Functional Divergence. Biomolecules, 12(6):783, https://doi.org/10.3390/biom12060783 (2022).
9. Alshammari, E., Zhang, Y., Yang. Z. Mechanistic and functional extrapolation of SMYD2 to pancreatic cancer. World Journal of Gastroenterology, 28(29):3753-3766, https://doi.org/10.3748/wjg.v28.i29.3753, (2022).
10. Mitchell, A., Wu, L., Block, J., Zhang, M., Craig, D., Chen, W., Zhao, Y., Zhang, B., Dang, Y., Zhang, X., Zhang, S., Wang, C., Pile, L., Kidder, B., Matherly, L., Yang, Z., Dou, Y., Wu, G.. FOXQ1 Hijacks the MLL Complex to Activate Transcription of the EMT Program and Promote Breast Cancer Metastatic Progression. Nature Communications, 13(1):6548, https://doi.org/10.1038/s41467-022-34239-z (2022).
11. Hou, Y., Sun, X., Gheinani, P., Guan, X., Sharma, S., Zhou, Y., Jin, C., Yang, Z., Naren, A., Yin, J., Denning, T., Gewirtz, A., Liu, Y., Xie, Z., Li, C. Epithelial SMYD5 Exaggerates IBD by Downregulating Mitochondrial Functions via Post-Translational Control of PGC-1α Stability. Cell Mol Gastroenterol Hepatol, S2352-345X(22)00088-1. https://doi.org/10.1016/j.jcmgh.2022.05.006 (2022).
12. Jeltema, D., Wang, J., Cai, J., Kelley, N., Yang, Z., He, Y. A single amino acid residue defines the difference in NLRP3 inflammasome activation between NEK7 and NEK6. The Journal of Immunology, 208(8):2029-2036, https://doi.org/10.4049/jimmunol.2101154 (2022).
13. Alshammari, E., Zhang, Y., Sobota, J., Yang, Z. Aberrant DNA methylation of tumor suppressor genes and oncogenes as cancer biomarkers. Genomic and Epigenomic Biomarkers of Toxicology and Disease, Wiley, https://doi.org/10.1002/9781119807704.ch12 (2022).
14. Zhang, Y., Alshammari, E., Sobota, J., Yang, Z. SMYD protein family as promising biomarkers for cancer diagnosis and prognosis. Genomic and Epigenomic Biomarkers of Toxicology and Disease, Wiley, https://doi.org/10.1002/9781119807704.ch13 (2022).
15. Sobota, J., Zhang, Y., Alshammari, E., Yang, Z. Emerging Non-Invasive Molecular Biomarkers for Early Cancer Detection. Genomic and Epigenomic Biomarkers of Toxicology and Disease, Wiley, https://doi.org/10.1002/9781119807704.ch11 (2022).
16. Zhang, Y., Yang, Z. Molecular Cloning and Purification of the Protein Lysine Methyltransferase SMYD2 and its Co-crystallization with a Target Peptide from Estrogen Receptor alpha. Methods in Molecular Biology, 2418:345-362 https://doi.org/10.1007/978-1-0716-1920-9_19, (2022).