Dr. Senlin Li's primary research interest is to develop
autologous hematopoietic stem cell transplantation (HSCT)-based cell and gene
therapy, including HSC-derived macrophage gene therapy for neurodegenerative
diseases such as Parkinson’s (to deliver neurotrophic factors to the brain) and
atherosclerosis (to provide antiatherogenic factors per se).
They have been
developing a novel HSCT technology that is non-cytotoxic and free of risk. This
invention, combined with the latest genome editing technologies (CRISPR/Cas9,
in particular), will greatly increase the willingness of patients and their
physicians to apply HSCT in treatment of disease.
Their lab works to extend his approach to
inherited and acquired blood/immune disorders including HIV/AIDS (by genome
editing to produce CCR5-/- and thus HIV-resistant blood cells).
With the same
platform, they are also interested in blood/immune rejuvenation. Finally, they keep
constant efforts to generate HSC from iPS cells.
Biju KC, Zhou Q, Li G, Imam SZ, Roberts RL, Morgan WW, Clark RA, and Li S. Macrophage-mediated GDNF delivery protects against dopaminergic neurodegeneration: A therapeutic strategy for Parkinson’s disease. Molecular Therapy 18:1536-1544,
Imam SZ, Zhou Q, Yamamoto A, Valente AJ, Ali SF, Bains
MC, Roberts JL, Kahle PJ, Clark RA, Li
S. Novel Regulation of Parkin Function Through c-Abl-Mediated Tyrosine Phosphorylation: Implications for Parkinson’s Disease. Journal of Neuroscience 31: 157–163, 2011.
Li G, Biju KC, Xu X, Zhou Q, Chen C, Valente AJ, He W, Reddick
RL, Freeman GL, Ahuja SS, Clark RA and Li
S. Macrophage LXRα gene therapy ameliorates atherosclerosis as well as hypertriglyceridemia in LDLR-/- mice. Gene
Therapy 18: 835–841, 2011.
KC, Santacruza RA, Chen C, Zhou Q, Yao J, Rohrabaugh SL, Clark RA, Roberts JL,
Phillips KA, Li S. Bone marrow-derived microglia based neurturin delivery protects against dopaminergic neurodegeneration in a mouse model of Parkinson‘s disease. Neurosci Lett 535:24-29, 2013.
Li X, Redus L, Chen C, Martinez PA, Strong R, Li S, and O'Connor JC. Cognitive dysfunction precedes the onset of motor symptoms in the MitoPark mouse model of Parkinson's disease. PLoS One 8:
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, Castrillo A. The Nuclear Receptor LXRa controls the functional specialization of splenic macrophages. Nature
Immunology 14: 831-839, 2013.