Li Laboratory

Mingjie Li, MD, PhD

Dr. Li received an M.D. from Jiamusi Medical College, China in 1983 and a Ph.D. from Kochi Medical School, Japan in 1994. He worked at Yale University studying immunoglobulin gene recombination and subsequently at the Beckman Research Institute of the City of Hope, California studying viral vector delivery of therapeutic genes against HIV infection before joining the Neurology Department at Washington University as an Assistant Research Professor in April, 2006.

Dr. Li serves as a Senior Scientist in the Viral Vectors Core at the Hope Center for Neurological Disorders. Gene delivery to nervous tissues is not only important for neuroscience research but also a potential means for the treatment of neurological disorders. However, most cell types relevant to nervous system disorders are difficult to transfect using non-viral transfection and traditional viral transduction methods. Genetic manipulation of brain cells in vivo has been even more challenging. Lentiviral vectors are able to transduce non-dividing cells, including neurons, making them attractive vehicles for gene delivery to neural cells. Several adeno-associated virus (AAV) serotypes have also been shown to successfully transduce cultured neurons and to mediate robust transgene expression in the brain.

We are developing new vectors for neurological applications. The goal of the Viral Vectors Core is to assist Washington University neuroscience researchers in the design and production of various kinds of vectors. Currently, we are focused on lentiviral and AAV vectors for use in cell culture and in vivo pre-clinical experiments designed to understand the causes and treatments for nervous system disorders. Among the projects we now undertaking are developing tissue-specific expression vectors and incorporating viral vectors with RNAi technology. We will also aim to promote translation of preclinical research findings into clinical applications.

Publications

  1. Li, M.J. Rossi, J.J. (2006) In DNA delivery/gene transfer. (Eds. T. Friedmann & J. Rossi) Cold Spring Harbor Laboratory Press. Lentivirus transduction of hematopoietic cells. (in press).
  2. Li, M.J. Rossi, J.J. (2006) In Gene Therapy Protocols. (Ed. J. Le Doux) Humana Press. Lentiviral-mediated delivery of siRNAs for gene therapy of HIV. (in press).
  3. Robbins, M.A., Li, M.J. Leung, I., Li, H., Boyer, D.V., Song, Y., Behlke, M.A., and Rossi, J.J., (2006) Stable expression of shRNAs in human CD34(+) progenitor cells can avoid induction of interferon responses to siRNAs in vitro. Nat Biotechnol, 24: 566-571.
  4. Unwalla, H.J., Li, H.T., Bahner, I., Li, M.J., Kohn, D., and Rossi, J.J., (2006) Novel Pol II fusion promoter directs human immunodeficiency virus type 1-inducible coexpression of a short hairpin RNA and protein. J Virol. 80:1863-1873.
  5. Li, M.J., Anderson, J., Kim, J., Li, S., Zaia, J., Yee, J.-K., Akkina, R. and Rossi, J.J. (2005) Long term inhibition of HIV-1 infection in primary hematopoietic cells by lentiviral vector delivery of a triple combination of anti-HIV shRNA, anti-CCR5 ribozyme and a nucleolar localizing TAR decoy. Mol. Ther 12: 900-909.
  6. Li, M.J. and Rossi, J.J. (2005) Lentiviral vector delivery of siRNA and shRNA encoding genes into cultured and primary hematopoietic cells. Methods in Molecular Biology 309: 261-272.
  7. Cook, H.L., Lytle, J.R., Mischo, H.E., Li, M.J., Rossi, J.J., Silva, D.P., Desrosiers, R.C. & Steitz, J.A. (2005) Small nuclear RNAs encoded by Herpesvirus saimiri upregulate the expression of genes linked to T cell activation in virally transformed T cells. Curr Biol 15: 974-979.
  8. Castanotto, D., Tommasi, S., Li, M.J., Li, H., Yanow, S., Pfeifer, G.P. & Rossi, J.J. (2005) Short hairpin RNA-directed cytosine (CpG) methylation of the RASSF1A gene promoter in HeLa cells. Mol. Ther 12: 179-183.
  9. Li, M.J. and Rossi, J.J. (2005) In Methods in Enzymology, RNA Interference, Volume 392, pp. 218-226, (Eds., J. Rossi and D.R. Engelke) Elsevier Inc., San Diego, CA. Lentiviral Vector Delivery of Recombinant Small Interfering RNA Expression Cassettes.
  10. Banerjea, A., Li, M.J., Remling. L., Rossi, J.J. and Akkina, R. (2004) Lentiviral transduction of Tar Decoy and CCR5 ribozyme into CD34+ progenitor cells and derivation of HIV-1 resistant T cells and macrophages. AIDS Res. and Therapy. 1: 2
  11. Unwalla, H., Li, M.J., Kim, J.D., Li, H.T. Ehsani, A., Alluin, J. and Rossi, J.J. (2004) Negative feedback inhibition of HIV-1 by TAT-inducible expression of siRNA. Nature Biotech. 22: 1573-1578.
  12. Li, M.J., McMahon, R., Snyder, D.S., Yee, J.-K., Rossi, J.J. (2003) Specific killing of Ph+ chronic myeloid leukemia cells by a lentiviral vector delivered anti-bcr/abl small hairpin RNA. Oligonucleotides 13: 401-409.
  13. Li, M.J., Bauer, G., Michienzi, A., Yee, J.-K., Lee, N.-S., Kim J., Li, S., Castanotto, D., Zaia, J.A. and Rossi, J.J. (2003) Inhibition of HIV-1 Infection by lentiviral vectors expressing Pol III-promoted anti-HIV RNAs. Mol Ther. 7: 196-206.
  14. Banerjea A, Li, M.J., Remling L, Lee N-S, Rossi J, Akkina R. (2003) Potent inhibition of HIV-1 by lentiviral vector transduced siRNAs in primary humanT-lymphocytes differentiated in SCID-hu mice and CD34+ progenitor cell derived macrophages. Molecular Therapy. 2003:8: 62-71.
  15. Akkina, R., Banerjea, A., Bai, J., Anderson, J., Li, M.J. and Rossi, J.J. (2003) siRNAs, ribozymes and RNA decoys in modeling stem cell-based gene therapy for HIV/AIDS. Anticancer Res. 23: 1997-2005.
  16. Lee, N.D., Dohjima, T., Bauer, G., Li, H. Li, M.J., Ehsani, A., Salvaterra, P. and Rossi, J.J. (2002) Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nat. Biotechol. 20: 446-448.

Dr. Li’s Contact Information

E-mail: lim@neuro.wustl.edu
Phone: (314) 747-1123
Fax: (314) 362-9462
Mailing address:
Washington University School of Medicine
660 S. Euclid
Campus Box 8111
St. Louis, MO 63110

Hope Center for Neurological Disorders

 

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