Jing Zhang, PHD

Pubmed

News Releases:

• Researchers Discover Early Step in Blood Stem Cell Development, 2 December 2013

More information:

• Jing Zhang Laboratory Home Page

Research Description:

My laboratory focuses on studying the mechanisms underlying the normal as well as oncogenic self-renewal of stem cells using the hematopoietic compartment as a model system. One of the molecules we have been studying is K-ras. K-ras is one of the most frequently mutated genes identified in human patients with various hematopoietic malignancies. The oncogenic mutations in the K-ras gene are acquired either as the first genetic change (1st hit) during leukemogenesis or one of the later genetic changes during leukemia progression. However, its precise roles in leukemogenesis and leukemia progression remain elusive. Using recipient mice transplanted with bone marrow cells expressing oncogenic K-ras from its endogenous promoter, we found that oncogenic K-ras mutations induce hematopoietic malignancies in multiple lineages. Based on our preliminary results, we hypothesize that when oncogenic K-ras mutations act as the 1st hit in leukemogenesis, its primary target is HSCs. Oncogenic K-ras mutations further co-operate with additional genetic change(s) occurring in lineage-committed progenitors to initiate and maintain hematopoietic malignant phenotypes.

Selected References:

• Kong, G., Wunderlich, M., Yang, D., Ranheim, E. A., Young, K. H., Wang, J., Chang, Y.-I., Du, J., Liu, Y., Tey, S. R., Zhang, X., Juckett, M., Mattison, R., Damnernsawad, A., Zhang, J., Mulloy, J. C., and Zhang, J. Combined MEK and JAK Inhibition Abrogates Murine Myeloproliferative Neoplasm. J. Clin. Invest., 124(6): 2762-2773, 2014.
• Wang, J., Kong, G., Liu, Y., Du, J., Chang, Y.-I., Tey, S. R., Zhang, X., Ranheim, E. A., Saba-El-Leil, M. K., Meloche, S., Damnernsawad, A., Zhang, J., and Zhang, J. NrasG12D/+ Promotes Leukemogenesis by Aberrantly Regulating Hematopoietic Stem Cell Functions. Blood, 121(26): 5203-5207, 2013.
• Du, J., Wang, J., Kong, G., Jiang, J., Zhang, J., Liu, Y., Tong, W., and Zhang, J. Signaling Profiling at the Single-Cell Level Identifies a Distinct Signaling Signature in Murine Hematopoietic Stem Cells. Stem Cells, 30: 1447-1454, 2012.
• Johnson, K. D., Hsu, A. P., Ryu, M.-J., Wang, J., Gao, X., Boyer, M. E., Liu, Y., Lee, Y., Calvo, K. R., Keles, S., Zhang, J., Holland, S. M., and Bresnick, E. H. Cis-Element Mutated in GATA2-Dependent Immunodeficiency Governs Hematopoiesis and Vascular Integrity. J. Clin. Invest., 122: 3692-3704, 2012.
• Wang, J., Liu, Y., Li, Z., Wang, Z., Tan, L. X., Ryu, M.-J., Meline, B., Du, J., Young, K. H., Ranheim, E., Chang, Q., and Zhang, J. Endogenous Oncogenic Nras Mutation Initiates Hematopoietic Malignancies in a Dose- and Cell Type-Dependent Manner. Blood, 118: 368-379, 2011.