Guangjun Zhang

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

Our current research is focusing two major directions: 1). Developmental patterning roles of bioelectricity and 2). Novel cancer driver gene discovery using comparative genetic approach. In addition, we are also interested in the developmental mechanisms of vertebrate morphological novelties during evolution (Evo-Devo), especially the roles of gene/genome duplications in early vertebrates. 1). Developmental patterning roles of bioelectricity and ion channels. Bioelectricity refers to endogenous electrical signaling mediated by ion channels and pumps located throughout the cell membrane. Cell membranes act as electrical insulators, in part, due to the phospholipid bilayer’s impermeability to ions. Any ion that forms a gradient across a membrane will contribute to the actual membrane potential and bioelectrical signaling. It is already known that mutations or malfunctions of potassium channel genes cause a variety of diseases in the central nervous system, heart, pancreas, and kidneys (long-QT syndromes, episodic ataxia, familial convulsions, etc.). However, the function of ion channels and bioelectricity are just being recognized in developmental biology. There is growing evidence that bioelectricity also plays an important role in vertebrate embryogenesis, wound healing, and cancer. Currently, we are focusing on the developmental roles of potassium channel genes zebrafish fin size and pigment patterns. 2). Novel cancer driver gene discovery using comparative oncogenomics. Most human cancer cell genomes contain thousands of genetic alterations. But not all the altered genes equally contribute to cancer development and progression. A major goal of current cancer research is to distinguish pathogenetically relevant genetic alterations (drivers) from the passive changes (passengers) in cancer genome, thus targeting therapy can be developed on human tumors. Our lab mainly uses zebrafish as a model to study human cancer biology of MPNSTs (malignant peripheral nerve sheath tumors). First, novel human cancer driver genes will be identified through zebrafish-human comparative oncogenomic analysis and zebrafish genetic models. Following identification, novel genes’ functions and mechanisms will be examined in cancer and vertebrate development. development. The new cancer driver genes will provide more information for not only cancer biology, but also guides on human cancer patient diagnosis, treatment and prognosis.

Selected Publications:

1. Silic, M.R., Murata, S.H., Park, S.J., Zhang, G. (2021). Evolution of inwardly rectifying potassium channels and their gene expression in zebrafish embryos. Developmental Dynamics. https://doi.org/10.1002/dvdy.425

2. Han, H., Jiang, G.Z., Kurami, R., Silic, M.R., Owens, J.L., Hu, C.D., Mittal, S.K., Zhang, G. (2021). Loss of smarcad1a accelerates tumorigenesis of malignant peripheral nerve sheath tumors in zebrafish. Genes, Chromosomes and Cancer. 60:743–761. https://doi.org/10.1002/gcc.22983

3. Silic, M.R, Maya M.B., Zhang, G. (2021). Phylogenetic and developmental analyses indicate complex functions of Calcium‐Activated Potassium Channels in zebrafish embryonic development. Developmental Dynamics. https://doi.org/10.1002/dvdy.329

4. Silic, M.R., Wu Q., Kim, B.H., Golling, G., Chen, K.H., Freitas, R., Chubykin, A.A., Mittal, S.K., and Zhang, G. (2020). Potassium Channel-Associated Bioelectricity of the Dermomyotome Determines Fin Patterning in Zebrafish. Genetics. 215: 1067-1084. https://doi.org/10.1534/genetics.120.303390

5. Kim BH, Zhang, G. (2020). Generating Stable Knockout Zebrafish Lines by Deleting Large Chromosomal Fragments Using Multiple gRNAs. G3: Genes|Genomes|Genetics. g3.401035.2019. https://doi.org/10.1534/g3.119.401035

6. Silic M.R., Zhang G. (2018). Visualization of Cellular Electrical Activity in Zebrafish Early Embryos and Tumors. JOVE, 134: e57330. https://dx.doi.org/10.3791/57330

7. Kumari K., Silic M.R., Jones-Hall Y.L., Nin-Velez A., Yang J.Y., Mittal S.K., Zhang G. (2018). Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors. Oncotarget, 9:23494-23504. https://doi.org/10.18632/oncotarget.25236

8. Cui Z, Shen, Y.J., Chen K.H., Mittal, S.K., Yang, J.Y., and Zhang, G. (2017). KANK1 inhibits cell growth by inducing apoptosis through regulating CXXC5 in human malignant peripheral nerve sheath tumors. Scientific Reports 7: 40325. https://doi.org/10.1038/srep40325

9. Tarazona, O.A., Slota, L.A., Lopez, D.H., Zhang, G. & Cohn, M.J. (2016) The genetic program for cartilage development has deep homology within Bilateria. Nature, 533: 86–89. https://doi.org/10.1038/nature17398

10. Hensley, M. R., Chua, R. F., Leung, Y. F., Yang, J. Y., Zhang, G. (2016) Molecular Evolution of MDM1, a "Duplication-Resistant" Gene in Vertebrates. PLoS One 11, e0163229. https://doi.org/10.1371/journal.pone.0163229

11. Hensley, M.R., Cui, Z., Chua, R.F.M., Simpson, S., Shammas, N.L., Yang, J.-Y., Leung, Y.F., and Zhang, G. (2016). Evolutionary and developmental analysis reveals KANK genes were co-opted for vertebrate vascular development. Scientific Reports 6, 27816. https://doi.org/10.1038/srep27816

12. Tarazona, O.A., Slota, L.A., Lopez, D.H., Zhang, G. & Cohn, M.J. (2016) The genetic program for cartilage development has deep homology within Bilateria. Nature, 533: 86–89. https://doi.org/10.1038/nature17398

13. Zhang G., Hoersch S., Amsterdam A., Whittaker C.A., Beert E., Catchen, J.M., Farrington, S., Postlethwait, J.H., Legius E., Hopkins, N., Lees, J.A. (2013) Comparative Oncogenomic Analysis of Copy Number Alterations in Human and Zebrafish Tumors Enables Cancer Driver Discovery. PLoS Genetics 9(8): e1003734. https://doi.org/10.1371/journal.pgen.1003734

14. Zhang G., Hoersch S., Amsterdam A., Whittaker C.A,. Lees J.A., Hopkins N. (2010). Highly aneuploid zebrafish malignant peripheral nerve sheath tumors have genetic alterations similar to human cancers. Proceedings of the National Academy of Sciences, 107: 16940–16945. https://doi.org/10.1073/pnas.1011548107

15. Zhang, G. and Cohn, M.J. (2006). Hagfish and lancelet fibrillar collagens reveal that type II collagen-based cartilage evolved in stem vertebrates. Proceedings of the National Academy of Sciences, 103: 16829-33. https://doi.org/10.1073/pnas.0605630103

16. Freitas, R., Zhang, G., Cohn, M.J. (2006). Evidence that mechanisms of fin development evolved in the midline of early vertebrates. Nature. 2006 442: 1033-7. https://doi.org/10.1038/nature04984

17. Zhang, G., Miyamoto, M.M., Cohn, M.J. (2006). Lamprey type II collagen and Sox9 reveal an ancient origin of the vertebrate collagenous skeleton. Proceedings of the National Academy of Sciences, 103: 3180-5. https://doi.org/10.1073/pnas.0508313103