Department of Biochemistry and Molecular Biology
Broad Center for Regenerative Medicine and Stem Cell Research
Keck School of Medicine
Research Topics1. Neural stem cell self-renewal and differentiation regulated by Ryk-mediated Wnt signaling. 2. Regulation of asymmetric cell division in neural stem cells. 3. Molecular mechanisms of Ryk-mediated Wnt signal transduction. 4. Molecular mechanism of somatic cell reprogramming.
Research OverviewNEURAL STEM CELLS
Human nervous system consists of billions of neurons and their supporting cells. These cells originally come from neural stem cells. During brain development, neural stem cells respond to the surrounding environment by either proliferative self-renewal or differentiation. Mishap of this process may cause developmental neurological diseases. The molecular mechanisms underlying neural stem cell self-renewal and differentiation are far from clear. Our laboratory studies the molecular mechanisms of neural stem cell self-renewal and differentiation. Particularly, we are interested in Wnt signaling in neural stem cells.
We focus our efforts on an atypical receptor tyrosine kinase named Ryk. We and others identified Ryk as a new receptor for Wnt, a secreted glycoprotein that play important roles in stem cell renewal and differentiation. Using Ryk siRNA transgenic mice and Ryk knockout mice, we have found that Ryk was required for axon guidance, neurite outgrowth and neural stem cell differentiation. Our current research focuses on Ryk’s role in the control of balance of symmetric and asymmetric cell division in neural stem cells, using Ryk knockout mice as well as neural stem cell culture. Using molecular genetic and biochemical approaches, we will define the Ryk-mediated Wnt signal transduction pathway by identifying the components in this pathway.
SOMATIC CELL REPROGRAMMING
Human ES cells are pluripotent and can differentiate into all cell types in our body. They have great potential for cell replacement therapy for degenerative diseases, including Alzheimer’s disease, Huntington disease, etc.. Induced pluripotent stem (iPS) cells are ES cell-like cells derived through somatic cell reprogramming. Another line of research in the lab is to study human and mouse somatic cell reprogramming. We study how neural stem cells and other somatic cells can be induced to iPS cells. We are particularly interested in how cell signaling interacts with the intrinsic transcription factors to re-establish pluripotency. We also establish patient- and disease-specific iPS cells to study human neurological diseases and use them for drug discovery.
- Web Sites:
- Stem Cell Center website
- Mailing Address:
- Broad Center for Regenerative Medicine and Stem Cell Research
KSOM of USC
1501 San Pablo Street, ZNI 523
Los Angeles, CA 90033
- Office Location:
- ZNI 523
- Office Phone:
- (323) 442-1618
- Lab Location:
- ZNI 521
- Lab Phone:
- B.S., Nankai University, 1990
- M.S., Beijing University, 1993
- Ph.D., Harvard University, 1998
- Postdoctoral Fellow, California Institute of Technology, 2005
Zhong, J., Kim, H., Lyu, J.,Yoshikawa, K Nakafuku, M. and Lu, W (2010),Wnt receptor Rykcontrols specification of GABAergic neurons versus oligodendrocytes duringtelencephalon development. Development,in press
Zhang, P., Adrianakos, R., Yang,Y. and Lu, W (2010), Kruppel-like factor 4 (KLF4) prevents embryonic stem (ES) cell differentiation by regulating Nanog gene expression, Journal of Biological Chemistry, 285(12):9180-9.-PubMed
Wei, Z., Yang, Y., Zhang, P.,Andrianakos, R., Hasegawa, K., Lyu, J., Chen, X., Bai, G., Liu, C., Pera, M.,and Lu, W. (2009) Klf4 directly interactswith Oct4 and Sox2 to promote reprogramming, Stem Cells, 27(12):2969-78.-PubMed
Lyu, J., Wesselschmidt, RL and Lu, W (2009). Cdc37 regulates Ryk signaling by stabilizing thecleaved Ryk intracellular domain, Journal of Biological Chemistry, 284(19):12940-8.-PubMed
Lyu, J, Yamamoto, V, and Lu W. (2008) Cleavage of Wnt receptor Ryk regulates neuronal differentiation during cortical neurogenesis.Developmental Cell. 15(5):773-80.-PubMed
Lu, W., Yamamoto, V., Ortega, B. and Baltimore, D. (2004).Mammalian Ryk is a Wnt coreceptor required for stimulation of neuriteoutgrowth. Cell. 119, 97-108.-PubMed