ZFIN ID: ZDB-PERS-021213-1
Zhu, Shizhen
Email: zhu.shizhen@mayo.edu
Affiliation: Jane Zhu Lab
Address: 221 4th Ave SW, Guggenheim 13-21C Rochester, MN 55902
Country: Singapore
Phone: 1-507-293-2558
Fax: 1-507-293-1058

Dr. Zhu's laboratory utilizes functional genomics approach and robust zebrafish model system to explore the contributions of findings emerging from integrative genomic studies to the pathogenesis of neuroblastoma and different types of cancers, and to translate the knowledge gained from experimental studies into effective therapy for these devastating malignancies.

Focus areas
1. Neuroblastoma pathogenesis. Dr. Zhu's laboratory focuses on i) exploring the in vivo contributions of new genetic findings emerging from integrative genomic studies to neuroblastoma pathogenesis, ii) uncovering molecular mechanisms that underlie the tumor initiation and progression, and iii) developing novel targeted therapies for this devastating childhood malignancy.

2. Tumor metastasis. By taking the advantage of an innovative zebrafish model of neuroblastoma metastasis, Dr. Zhu is particularly interested in defining the mechanisms underlying the metastasis of neuroblastoma cells in vivo and identifying novel genes and pathways are critical for this metastatic disease using novel forward and reverse genetic approaches.

3. Phosphatase signaling in tumorigenesis. An additional area of focus is to understand the role of aberrantly regulated phosphatases signaling, including the SHP2 and the PTPRD tyrosine phosphatases and their pathways, in malignant transformation and progression of neuroblastoma and different types of cancers.

Anderson, N.M., Qin, X., Finan, J.M., Lam, A., Athoe, J., Missiaen, R., Skuli, N., Kennedy, A., Saini, A.S., Tao, T., Zhu, S., Nissim, I., Look, A.T., Qing, G., Simon, M.C., Feng, H. (2021) Metabolic Enzyme DLST Promotes Tumor Aggression and Reveals a Vulnerability to OXPHOS Inhibition in High-Risk Neuroblastoma. Cancer research. 81(17):4417-4430
Dong, Z., Yeo, K.S., Lopez, G., Zhang, C., Dankert Eggum, E.N., Rokita, J.L., Ung, C.Y., Levee, T.M., Her, Z.P., Howe, C.J., Hou, X., van Ree, J.H., Li, S., He, S., Tao, T., Fritchie, K., Torres-Mora, J., Lehman, J.S., Meves, A., Razidlo, G.L., Rathi, K.S., Weroha, S.J., Look, A.T., van Deursen, J.M., Li, H., Westendorf, J.J., Maris, J.M., Zhu, S. (2021) GAS7 Deficiency Promotes Metastasis in MYCN-driven Neuroblastoma. Cancer research. 81(11):2995-3007
Koach, J., Holien, J.K., Massudi, H., Carter, D.R., Ciampa, O.C., Herath, M., Lim, T., Seneviratne, J.A., Milazzo, G., Murray, J.E., McCarroll, J.A., Liu, B., Mayoh, C., Keenan, B., Stevenson, B.W., Gorman, M.A., Bell, J.L., Doughty, L., Hüttelmaier, S., Oberthuer, A., Fischer, M., Gifford, A.J., Liu, T., Zhang, X., Zhu, S., Gustafson, W.C., Haber, M., Norris, M.D., Fletcher, J.I., Perini, G., Parker, M.W., Cheung, B.B., Marshall, G.M. (2019) Drugging MYCN Oncogenic Signaling through the MYCN-PA2G4 Binding Interface. Cancer research. 79:5652-5667
Zimmerman, M.W., Liu, Y., He, S., Durbin, A.D., Abraham, B.J., Easton, J., Shao, Y., Xu, B., Zhu, S., Zhang, X., Li, Z., Weichert-Leahey, N., Young, R.A., Zhang, J., Look, A.T. (2018) MYC Drives a Subset of High-Risk Pediatric Neuroblastomas and Is Activated through Mechanisms Including Enhancer Hijacking and Focal Enhancer Amplification. Cancer discovery. 8:320-335
Zhu, S., Zhang, X., Weichert-Leahey, N., Dong, Z., Zhang, C., Lopez, G., Tao, T., He, S., Wood, A.C., Oldridge, D., Ung, C.Y., van Ree, J.H., Khan, A., Salazar, B.M., Lummertz da Rocha, E., Zimmerman, M.W., Guo, F., Cao, H., Hou, X., Weroha, S.J., Perez-Atayde, A.R., Neuberg, D.S., Meves, A., McNiven, M.A., van Deursen, J.M., Li, H., Maris, J.M., Look, A.T. (2017) LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis. Cancer Cell. 32(3):310-323.e5
Tao, T., Sondalle, S.B., Shi, H., Zhu, S., Perez-Atayde, A.R., Peng, J., Baserga, S.J., Look, A.T. (2017) The pre-rRNA processing factor DEF is rate limiting for the pathogenesis of MYCN-driven neuroblastoma. Oncogene. 36(27):3852-3867
Zhang, X., Dong, Z., Zhang, C., Ung, C.Y., He, S., Tao, T., Oliveira, A.M., Meves, A., Ji, B., Look, A.T., Li, H., Neel, B.G., Zhu, S. (2017) Critical Role for GAB2 in Neuroblastoma Pathogenesis through the Promotion of SHP2/MYCN Cooperation. Cell Reports. 18:2932-2942
He, S., Mansour, M.R., Zimmerman, M.W., Ki, D.H., Layden, H.M., Akahane, K., Gjini, E., de Groh, E.D., Perez-Atayde, A.R., Zhu, S., Epstein, J.A., Look, A.T. (2016) Synergy between loss of NF1 and overexpression of MYCN in neuroblastoma is mediated by the GAP-related domain. eLIFE. 5
Zhu, S., Look, A. T. (2016) Neuroblastoma and Its Zebrafish Model. Advances in experimental medicine and biology. 916:451-78
Ung, C.Y., Guo, F., Zhang, X., Zhu, Z., Zhu, S. (2015) Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis. Journal of visualized experiments : JoVE. (97)
Zhu, S., Lee, J.S., Guo, F., Shin, J., Perez-Atayde, A.R., Kutok, J.L., Rodig, S.J., Neuberg, D.S., Helman, D., Feng, H., Stewart, R.A., Wang, W., George, R.E., Kanki, J.P., and Look, A.T. (2012) Activated ALK Collaborates with MYCN in Neuroblastoma Pathogenesis. Cancer Cell. 21(3):362-373
Zhu, S., Low, B.C. (2012) Using Zebrafish for Studying Rho GTPases Signaling In Vivo. Methods in molecular biology (Clifton, N.J.). 827:321-337
Gutierrez, A., Grebliunaite, R., Feng, H., Kozakewich, E., Zhu, S., Guo, F., Payne, E., Mansour, M., Dahlberg, S.E., Neuberg, D.S., Hertog, J.D., Prochownik, E.V., Testa, J.R., Harris, M., Kanki, J.P., and Look, A.T. (2011) Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia. The Journal of experimental medicine. 208(8):1595-603
Lee, J.S., Padmanabhan, A., Shin, J., Zhu, S., Guo, F., Kanki, J.P., Epstein, J.A., and Look, A.T. (2010) Oligodendrocyte progenitor cell numbers and migration are regulated by the zebrafish orthologs of the NF1 tumor suppressor gene. Human molecular genetics. 19(23):4643-4653
Stewart, R.A., Sanda, T., Widlund, H.R., Zhu, S., Swanson, K.D., Hurley, A.D., Bentires-Alj, M., Fisher, D.E., Kontaridis, M.I., Look, A.T., and Neel, B.G. (2010) Phosphatase-Dependent and -Independent Functions of Shp2 in Neural Crest Cells Underlie LEOPARD Syndrome Pathogenesis. Developmental Cell. 18(5):750-762
Liu, L., Zhu, S., Gong, Z., and Low, B.C. (2008) K-ras/PI3K-Akt signaling is essential for zebrafish hematopoiesis and angiogenesis. PLoS One. 3(8):e2850
Zhu, S., Korzh, V., Gong, Z., and Low, B.C. (2008) RhoA prevents apoptosis during zebrafish embryogenesis through activation of Mek/Erk pathway. Oncogene. 27(11):1580-1589
Zhu, S., Liu, L., Korzh, V., Gong, Z., and Low, B.C. (2006) RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements by involving effectors Rho Kinase and Diaphanous: Use of zebrafish as an in vivo model for GTPase signaling. Cellular Signalling. 18(3):359-372

Oldridge DA, Wood AC, Weichert-Leahey N, Crimmins I, Sussman R, Winter C, McDaniel LD, Diamond M, Hart LS, Zhu S, Durbin AD, Abraham BJ, Anders L, Tian L, Zhang S, Wei JS, Khan J, Bramlett K, Rahman N, Capasso M, Iolascon A, Gerhard DS, Guidry Auvil JM, Young RA, Hakonarson H, Diskin SJ, Thomas Look A, Maris JM. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism. Nature. 2015, Nov, PMID: 26560027.