We are interested in using mouse genetics to study the molecular and cellular mechanisms underlying initiation and progression of tumors in the both central nervous system (CNS) and peripheral nervous system (PNS). We have employed mouse genetics to develop genetic engineering mouse (GEM) tumor models, which recapitulate human cancer both genetically and phenotypically. In particular, we have generated a series of mouse models for tumors of the nervous system. By using a germline mutation at the p53 gene and a conditional mutation at the Neurofibromatosis type 1 (NF1) gene, we generated mouse models for astrocytoma and glioblastoma multiforme (GBM) in the CNS as well as neurofibroma and malignant peripheral nerve sheath tumor (MPNST) in the PNS. We are exploring these mouse models to address: (1) whether neural stem/progenitor cells or differentiated cells are the cellular targets for tumors of the nervous system, (2) how the tumor suppressor genes regulate growth and transformation of neural stem/progenitor cells in vivo and in vitro, and (3) whether there are stem cell-like cells or cancer stem cells in astrocytomas and peripheral nerve sheath tumors.
1987-1991 B.S. in Biochemistry with honor of "Excellent Graduate of the University", Fudan University, Shanghai, P.R. China
1991-1994 Graduate Student, Department of Biochemistry, Fudan University, Shanghai, P.R. China
1994-2000 Ph.D. Program in Neuroscience, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
2000-2003 Research Fellow, Center for Developmental Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX
Honors and Awards
1991 "Excellent Graduate of Fudan University"
1992 “Guanghua" Scholarship
1998 30th Sigma Xi Chapter Award (UT, Southwestern Med.Ctr.)
2000 Travel Scholarship from National Neurofibromatosis Foundation Inc., (New York)
2001 “Scholar in Training Award” from American Association for Cancer Research (AACR) Inc.
2001-2003 “Young Investigator Award” from National Neurofibromatosis Foundation Inc. (New York)
2002 “Scholar in Training Award” from American Association for Cancer Research (AACR) Inc.
2002 “NF1 Research Prize” from National Neurofibromatosis Foundation Inc. (New York)
2003-2006 Biological Sciences Scholars Program (BSSP) Scholar, University of Michigan Medical School
2004-2006 General Motors Cancer Research Scholars Program Scholar, General Motors Foundation
2005-2007 Brain Tumor Society Research Grant Award, Brain Tumor Society
2005-2009 Investigator-initiated Research Award, Department of Defense Neurofibromatosis Research Program
2005-2009 American Cancer Society Research Scholar, American Cancer Society
Zhu, Y., Richardson, J.A., Parada, L.F. and Graff, J.M. (1998). Smad3 mutant mice develop metastatic colorectal cancel. Cell, Vol. 94 703-714.
Zhu, Y. and Parada, L.F. (2001). A special GAP in mind. Nature Genetics, 27:354-355.
Zhu, Y., Romero, M., Ghosh, P., Ye, Z., Charnay, P., Rushing, E.J., Marth, J.D. and Parada, L.F. (2001). Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes & Development, 15:859-876.
Zhu, Y., Gosh, P., Charnay, Burns, D.K. and Parada, L.F. (2002). Neurofibromas in NF1: Schwann cell origin and role of tumor environmnent. Science, 296:920-922.
Zhu, Y., and Parada, L.F. (2002). Molecular biology and genetics of neurologic tumors. Nature Reviews Cancer, 2:616-626.
Gitler, A.D.*, Zhu, Y.*, Ismat, F.A., Lu, M.M., Yamauchi, Y., Parada, L.F. and Epstein, J.A. (2003). The type 1 Neurofibromatosis (Nf1) gene product has distinct and essential roles in neural crest and endothelial cells. Nature Genetics, 33: 75-79. (*Both of these authors contributed equally to this work).
Joseph, N.M., Mosher, J.T., Buchstaller, J., Snider, P., McKeever, P.E., Lim, M., Conway, S.J., Parada, L.F., Zhu, Y. and Morrison, S.J. (2008). The loss of Nf1 transiently promotes self-renewal but not tumorigenesis by neural crest stem cells. Cancer Cell, in press.
Project 1: The role of neural stem/progenitor cells in the development of astrocytoma and glioblastoma.
Project 2: Molecular mechanisms underlying the initiation and progression of malignant astrocytoma.
Project 3: Molecular and cellular basis of the development of benign and malignant peripheral nerve sheath tumors.
Project 4: Genetic analysis of tumor suppressor genes in the development of the nervous system.
Additional Lab Links
Post-Doctoral Research Fellows:
Research Technician Associates:
Lindsey Cregan, B.S., email@example.com