RESEARCH PROGRAMS AND AFFILIATIONS
Brain plasticity; molecular, cellular and functional mechanisms of brain repair in traumatic brain injury, stroke, Alzheimer’s disease, and CADASIL. Pathological mechanisms underlying the development and progression of brain injury, neurodegenerative and genetic diseases.
ASSOCIATIONS / MEMBERSHIPS
The long-term goal of our research is to develop new therapeutic strategies for stroke, Alzheimer's disease, CADASIL disease, and traumatic brain injury.
Our current research focuses on enhancing brain repair after brain damage by either brain disease or injury. The major approaches used for our study include molecular biology, cellular biology, microsurgery, live brain imaging, flow cytometry, motor function and cognitive function assessment, immunohistochemistry and brain section imaging.
Stroke is considered a brain attack and is ranked as the number one cause of long-term disability in adults. Alzheimer's disease (AD) is a neurodegenerative disease that causes irreversible progressive brain damage and memory loss. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary stroke disorder and an autosomal dominant vascular dementia. Currently, there is no drug that can improve the functional outcome for stroke nor is there a treatment that can stop or delay the progressive brain damage caused by AD or CADASIL.
We have recently demonstrated the therapeutic effects of bone marrow stem cell factors on brain repair in animal models of stroke, Alzheimer's disease and CADASIL disease. Our laboratory is studying how the bone marrow stem cell factors repair the brain in these devastating diseases. In addition to the in vivo study, we are also determining how the bone marrow stem cell factors regulate neuronal process formation, synaptic generation, and stem cell growth, motility and differentiation. We are also gaining an understanding of the detailed process of how stem cells promote neuronal network development.
1. Zhao L.-R., Duan W.-M., Reyes M., Keene C.D., Verfaille C.M. Low W.C. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting to ischemic brain in rats. Experimental Neurology, 2002; 174: 11-20.
2. Zhao LR, Singhal S, Duan WM, Mehta J, Kessler JA. Brain repair by hematopoietic growth factors in a rat model of stroke. Stroke, 2007; 38:2584-2591.
3. Zhao LR, Berra HH, Duan WM, Singhal S, Mehta J, Apkarian AV, Kessler JA. Beneficial effects of hematopoietic growth factor therapy in chronic ischemic stroke in rats. Stroke, 2007; 38:2804-2811.
4. Zhao LR, Navalitloha Y, Singhal S, Mehta J, Kessler JA, Piao CS, Guo WP, Groothuis DR. Hematopoietic growth factors pass through the brain-blood barrier in intact rats. Experimental Neurology, 2007; 204:569-573.
5. C-S Piao, M E Gonzalez-Toledo, Y-Q Xue, W-M Duan, S Terao, D N Granger, R E Kelley and L-R Zhao. The role of stem cell factor and granulocyte-colony stimulation factor in brain repair during chronic stroke. JCBFM. 2009; 29:759-770.
6. Bin Li, Maria E Gonzalez-Toledo, Chun-Shu Piao, Allen Gu, Roger E Kelley, Li-Ru Zhao. Stem cell factor and granulocyte-colony stimulating factor reduce β-amyloid deposits in the brains of APP/PS1 transgenic mice. Alzheimer's Research & Therapy. 2011; 3:8.
7. Piao CS, Li Bin, Lijuang Zhang, Zhao LR*. Stem Cell Factor and Granulocyte-Colony Stimulating Factor Promotes Neurogenesis and Inhibits Glial Differentiation. Differentiation, 2012;83:17-25.
8. Lili Cui, Sasidhar R. Murikinati, D Wang, Xiangjian Zhang, Wei-Ming Duan, Li-Ru Zhao. Reestablishing neuronal networks in the aged brain by stem cell factor and granulocyte-colony stimulating factor in a mouse model of chronic stroke. PLoS ONE. 2013;8:e64684.