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

How the “marriage” between SET and MYND domains made SMYD proteins so special

SMYD proteins are a special class of protein lysine methyltransferases with an MYND domain inserted into a SET domain. Structurally, these two functional domains are intimately bundled, with a conserved architecture and being integrated into a single coherent structural module. The evolutionary history of SMYD proteins is dated back to at least 1.5 billion years ago at the beginning of eukaryotic life. They are present in both vertebrate and invertebrate animals. They are also present in choanoflagellates. Choanoflagellates are a group of free-living unicellular eukaryotes and considered to be the closest living unicellular relatives of the animals. SMYD proteins are also present in both higher and lower plants: the higher plants such as Arabidopsis thaliana, soy bean, and corn; the lower plants such as Ostreococcus tauri. Ostreococcus tauri is a marine green algae, unicellular, and is the smallest free-living eukaryote yet described. SMYD proteins are also present in amoeba. Amoeba are a group of single-celled organisms that possess pseudopods or move by protoplasmic flow. So you can see, SMYD proteins are conserved across eukaryotic species, from simple, single-celled organisms to more complex multicellular life, from marine organisms to land species, and from sessile plants to motile animals. A suggestion from this wide presence is: SMYD proteins are functionally important and might be involved in some core biological processes that are conserved in eukaryotes.

However, what selective pressure has driven the “marriage” of the SET and MYND domains and what specific function has evolved at the time of this marriage, remain unclear. From the time when SMYD1, the founding member of the SMYD protein family, was identified as being required for cardiomyocyte differentiation, our understanding of the structure and function of SMYD proteins has been steadily increasing. To date, we have known that not only are they involved in heart and skeletal muscle development, but also have diverse other roles in both normal biology and disease states, ranging from tumor cell proliferation, cancer stemness and dormancy, the immune response, to a very recent association with ciliogenesis via regulating microtubule dynamics. While the scope of SMYD protein research has been broadened significantly over the past two decades, it is becoming increasingly clear to us that the more we learn about their multifunctionality and multispecificity, the more we realize that there are more yet to be discovered. With the thriving of functional genomics studies, new research ideas are emerging in uncharted areas, including but not limited to mitochondrial and nucleolar ribosome biogenesis, RNA biology in stress granules, intellectual disability, calcium-dependent signaling, as well as sperm chromatin remodeling at fertilization.

The main goal of our research is to uncover new paradigms in SMYD protein research while further broadening our understanding of their functional diversity. As our knowledge develops and advances, we want to conclude that the marriage between the SET and MYND domains that made SMYD proteins so special is an ultimate rule governing their past, present and future.

Publications

• Yang, A., Zhang, Y. and Yang, Z. Artificial intelligence and machine learning of single-cell transcriptomics of engineered nanoparticles. Engineered Nanomaterials in Genomics and Epigenomics, Wiley, in press (2023).
• Zhang, Y., Alshammari, E., Yonis, N. and Yang, Z. Adverse epigenetic effects of environmental engineered nanoparticles as drug carriers. Engineered Nanomaterials in Genomics and Epigenomics, Wiley, in press (2023).
• Alshammari, E., Zhang, Y., Yang, A. and Yang, Z. Toxicogenomics and toxicological mechanisms of engineered nanomaterials. Engineered Nanomaterials in Genomics and Epigenomics, Wiley, in press (2023).
• Zhang, Y., Yang, A. and Yang, Z. Engineered nanoparticles adversely impact glucose energy metabolism. Engineered Nanomaterials in Genomics and Epigenomics, Wiley, in press (2023).
• Yonis, N, Alshammari, E., Zhang, Y. and Yang, Z. Carbon nanotubes alter metabolomics pathways leading to toxicity. Engineered Nanomaterials in Genomics and Epigenomics, Wiley, in press (2023).
• 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, doi: 10.3390/biom12060783 (2022).
• Alshammari, E., Zhang, Y. and Yang, Z. Mechanistic and functional extrapolation of SET and MYND domain-containing protein 2 to pancreatic cancer. World J Gastroenterol 2022; 28(29): 3753-3766, doi: 10.3748/wjg.v28.i29.3753 (2022).
• 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. and 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. doi: 10.1016/j.jcmgh.2022.05.006 (2022).
• Jeltema, D., Wang, J., Cai, J., Kelley, N., Yang, Z. and 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, doi: 10.4049/jimmunol.2101154 (2022).
• Zhang, Y. and 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 doi: 10.1007/978-1-0716-1920-9_19, (2022).
• Zhang, Y., Alshammari, E., Sobota, J. and Yang, Z. SMYD protein family as promising biomarkers for cancer diagnosis and prognosis. Genomic and Epigenomic Biomarkers of Toxicology and Disease, Wiley, doi: 10.1002/9781119807704.ch13 (2022).
• Alshammari, E., Zhang, Y., Sobota, J. and Yang, Z. Aberrant DNA methylation of tumor suppressor genes and oncogenes as cancer biomarkers. Genomic and Epigenomic Biomarkers of Toxicology and Disease, Wiley, doi: 10.1002/9781119807704.ch12 (2022).
• Sobota, J., Zhang, Y., Alshammari, E. and Yang, Z. Emerging Non-Invasive Molecular Biomarkers for Early Cancer Detection. Genomic and Epigenomic Biomarkers of Toxicology and Disease, Wiley, doi: 10.1002/9781119807704.ch11 (2022).
• Zhang, Y., Hayden, S., Spellmon N., Xue, W., Martin, K., Muzzarelli, K., Kovari, L. and Yang, Z. Sperm chromatin-condensing protamine enhances SMYD5 thermal stability. Biochem Biophys Res Commun,550(1):1-7, doi: 10.1016/j.bbrc.2021.02.073 (2021).
• Yang, Z. How the “marriage” between SET and MYND domains made SMYD proteins so special. Biomolecules, https://www.mdpi.com/journal/biomolecules/special_issues/SMYD_Proteins (2021).
• Hou, Y., Sun, X., Gheinani, P., Guan, X., Sharma, S., Zhou, Y., Jin, C., Yang, Z., Naren, A., Yin, J., Denning, T., Gewirtz, A., Xie, Z. and Li, C. METHYLTRANSFERASE SMYD5 EXAGGERATES INFLAMMATORY BOWEL DISEASE BY REGULATING PPAR-γ COACTIVATOR 1-α STABILITY. Gastroenterology, 160(3):S35-S36, 10.1053/j.gastro.2021.01.104, (2021).
• Hou, Y., Sun, X., Gheinani, P., Guan, X., Sharma, S., Zhou, Y., Jin, C., Yang, Z., Naren, A., Yin, J., Denning, T., Gewirtz, A., Xie, Z. and Li, C. METHYLTRANSFERASE SMYD5 EXAGGERATES INFLAMMATORY BOWEL DISEASE BY REGULATING PPAR-γ COACTIVATOR 1-α STABILITY. Inflammatory Bowel Diseases, 27:S27-S27, doi: 10.1093/ibd/izaa347.061, (2021).
• Qin, Z, Ou, S., Xu, L., Sorensen, K., Zhang, Y., Yang, Z., Hu, W. and Chen, F. Design, synthesis of isothiocyanate-containing hybrid androgen receptor (AR) antagonist to downregulate AR and induce ferroptosis in GSH–deficient prostate cancer cells. Chemical Biology & Drug Design, doi: 10.1111/cbdd.13826 (2021).

 

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