PHARMACOLOGY FACULTY
Selected Publications
  • Biju, KC., Santacruza, RA., Chen, C., Zhou, Q., Yao, J., Rohrabaugh, SL., Clark, RA., Roberts, JL., Phillips, KA. and Li S. (2013) Bone marrow-derived microglia based neurturin delivery protects against dopaminergic neurodegeneration in a mouse model of Parkinson‘s disease. Neurosci Lett 535:24-29.
  • Xiao, W., Peng, Y., Liu, Y., Li, Z., Li S. and Zheng, X. (2013) HSCARG Inhibits NADPH Oxidase Activity through Regulation of the Expression of p47phox. PLoS ONE 8:e59301-e59311.
  • A-Gonzalez, N., Guillen, JA., Gallardo, G., Diaz, M., de la Rosa, JV., Hernandez, IH., Casanova-Acebes, M., Lopez, F., Tabraue, C., Beceiro, S., Hong, C., Lara, PC., Andujar, M., Arai, S., Miyazaki, T., Li, S., Corbi, AL., Tontonoz, P., Hidalgo, A. and Castrillo, A. (2013) The Nuclear Receptor LXRa controls the functional specialization of splenic macrophages. Nature Immunology 14:831-839.
  • Imam, S., Binienda, Z., Paule, M., Slikker, W., Clark, RA., Li, S. and Ali, S. (2013) Neuroprotective efficacy of a new brain-penetrating c-Abl inhibitor in a murine Parkinson‘s disease model. PLoS ONE 8(5):e65129-e65136.
  • Li, X., Redus, L., Chen, C., Martinez, PA., Strong,, R., Li, S. (co-correspondent author) and Oconnor, J. (2013) Cognitive dysfunction precedes the onset of motor symptoms in the MitoPark mouse model of Parkinson‘s Disease. PLoS ONE 8:e71341-e71351.
  • Levin, MC., Lidberg, U., Jirholt, P., Adiels, M., Wramstedt, A., Gustafsson, K., Greaves, DR., Li, S., Fazio, S., Linton, MF., Olofsson, SO., Borén, J. and Gjertsson I. (2012) Evaluation of macrophage-specific promoters using lentiviral delivery in mice. Gene Therapy 19:1041-1047.
  • Li, G., Biju, KC., Xu, X., Valente, AJ., Reddick, RL., Freeman, GL., Ahuja, SS., Clark, RA. and Li, S. (2011) Macrophage LXRa gene therapy ameliorates atherosclerosis as well as hypertriglyceridemia in LDLR-/- mice. Gene Therapy 18(8):835-841.
  • Imam, SZ., Zhou, Q., Yamamoto, A., Valente, AJ., Ali, SF., Bains, M., Roberts, JL., Kahle, PJ., Clark, RA. and Li, S. (2011) Novel regulation of parkin function through c-Abl-mediated tyrosine phosphorylation: implications for Parkinson‘s disease. J Neurosci 31(1):157-163.
  • Biju, KC., Zhou, Q., Li, Q., Imam, S., Roberts, JL., Morgan, WW., Clark, RA. and Li, S. (2010) Macrophage-mediated GDNF delivery protects against dopaminergic neurodegeneration: A therapeutic strategy for Parkinson's disease. Molecular Therapy 18:1536-1544.
Senlin Li
 

Senlin Li

Associate Professor of Medicine and Pharmacology
M.D., University of Geneva

Office: 210-567-1905
Email: lis1@uthscsa.edu

 

Keywords

Parkinson's disease, neurodegenerative diseases, stem cell, iPS, hematopoietic stem cell, stem cell therapy, gene therapy, and altherosclerosis

 

Research Summary

My primary research interest is to develop autologous hematopoietic stem cell (HSC) gene therapy, particularly HSC-derived macrophage gene therapy for neurodegenerative diseases, atherosclerosis and other inherited blood/immune disorders.

 

Li lab group

 

Macrophages are recruited from bone marrow to most tissues of the body, including the central nervous system, thus making them an attractive option to deliver therapeutic genes. In macrophage-mediated gene therapy, HSCs will be mobilized from bone marrow, isolated from peripheral blood by apheresis, and transduced ex vivo to establish stable inegration of therapeutic genes. The transduced HSCs are given back to the same patients and the engraftment will form various lineages of blood cells, including macrophages. Because they are under the control of macrophage-specific promoters, the therapeutic genes will be expressed at high levels specifically in macrophages.

 

Neurotrophic factors that may be beneficial to degenerating neurons include glial cell-derived neurotrophic factor for Parkinson's disease and nerve growth factor for Alzheimer's disease. In addition, over-expression of apoE, apoAI, or LXR (liver X receptor) in macrophages has been shown to ameliorate atherosclerosis. These projects capitalize on powerful reagents, including super-macrophage promoters that we have recently developed and lentiviral vectors, which are superior in transduction of HSCs while maintaining their stem cell nature.

 

Embryonic stem (ES) cells are amenable to genetic modification and can be cultured indefinitely, therefore providing unlimited supplies. The recently-developed iPS (induced pluripotent stem) cells share these properties. Mouse ES and iPS cells have been differentiated in vitro into HSCs capable of rescuing leathally-irradiated syngeneic recipients. HSCs so created may offer potential rejuvenation of the blood cells of older individuals by administration of youthful cells. This type of HSC will likely be the best carrier for the gene therapy constructs described above.

 

Other ongoing projects in Dr. Li's laboratory include transcriptional regulation of PD-related genes, genome-wide mapping of histone acetylation in cancer cells, age-related oxidative DNA damage and repair, and cellular mechanism of parkin in neurodegenerative diseases.