PHARMACOLOGY FACULTY
Selected Publications
  • Imam SZ, Sriram SR, Liao X, Ko HS, Savitt JM, Zhou Q, Pearson DW, Yamamoto A, Valente AJ, Andres-Mateos E, Trinkaus DB, Schools SE, Pletnikova O, Troncoso JC, Ali SF, Bains MC, Roberts JL, Kahle PJ, Dawson VL, Clark RA, Li S, and Dawson TM. Inhibition of Parkin's E3 ubiquitin ligase activity through c-Abl-mediated tyrosine phosphorylation: Implications for Parkinson's Disease. Nature Medicine, (in press).
  • Valente AJ, Zhou Q, Qiang M, Lu Z, He W, Ma W, Li G, Wang L, Banfi B, Krause K-H, Clark RA, and Li S. Regulation of NOX1 expression by GATA, HNF-1α and CDX transcription factors. Free Radical Biology and Medicine. 44:430-443, 2008.
  • He W, Qiang M, Ma W, Valente AJ, Quinones M, Wang W, Reddick RL, Qifu X, Ahuja SS, Clark RA, Freeman GL, and Li S. Development of a synthetic promoter for macrophage gene therapy. Human Gene Therapy 11:949-959, 2006.
  • Zhao S, Venkatasubbarao K, Li S, Freeman JW. Requirement of a specific Sp1 site for HDAC-mediated repression of transforming growth factor bata type II receptor expression in human cancer cells. Cancer Research 63:2624-2630, 2003.
  • Li S, Valente AJ, and Clark RA. Multiple PU.1 binding is required for p40phox gene transcription in myeloid cells. Blood 99:4578-4587, 2002.
  • Li S, Valente AJ, Wang L, Gamez MJ, and Clark RA. Transcriptional regulation of the p67phox gene: Role of AP-1 in concert with myeloid-specific transcription factors. J Biol Chem 276:39368-39378, 2001.
  • Li S, Schlegel W, Valente AJ, and Clark RA. Critical flanking sequences of PU.1 binding sites in myeloid-specific promoters. J Biol Chem 274:32453-32460, 1999.
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.