The Luo Laboratory focuses on developing cell replacement therapy for neurodegenerative disease, including Parkinson’s disease (PD), stroke and traumatic brain injury.
- Endogenous neurogenesis in stroke.
Current treatment strategies for stroke primarily focus on reducing the size of ischemic damage and on rescuing dying cells early after occurrence. Treatments, such as the use of thrombolytic agents, are often limited by a narrow therapeutic time window. Cerebral ischemia can also activate endogenous repair processes. Our goal is to understand the role of neural progenitor cells (NPCs) and reactive astrocytes that acquire stem cell properties during brain injury recovery. The long-term goal of our research is to determine the molecular basis of SVZ/SGZ or local neurogenesis at the injury sites and to identify novel therapeutic strategies for expanding the treatment window for brain injuries such as stroke. My laboratory utilizes combined strategies such as inducible cell-type specific or activity-dependant gene modification in animal models and pharmacological manipulations of molecular pathways to gain a comprehensive understanding of key molecular pathways that contribute to CNS regeneration.
- Cell replacement therapy in PD.
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders. Clinical symptoms of PD do not manifest until 60-80% of DA neurons have been affected. This presents a challenge for the treatment of the disease since when patient is diagnosed the disease has progressed to a significant pathological degree. Parkinson’s disease has been an attractive target for cell replacement therapy because the main pathology underlying PD symptoms is a progressive degeneration of mesencephalic dopamine neurons. Replacement of dopaminergic neurons and reinnervation of the target area (striatum) have been the major goals in PD cell replacement therapy.However, the survival rate of the transplanted cells is low. Research projects in our laboratory include studying the role of apoptotic process in neuronal death in PD. Similar processes might also be responsible for the death of transplanted cells.We have generated modified ES cells in which certain genes will be specifically inactivated upon differentiation to dopaminergic neurons. By examining the survival and efficacy of transplantation of these modified ES cells, it will be possible to identify genetic pathways that will improve the survival and functional outcome of cell transplantation in PD. Our long term goal is to develop pharmacological treatments that modify these critical pathways that will result in improved survival of transplanted cells and better functional recovery in PD treatment.
1. Emily Filichia, Barry Hoffer, Xin Qi, Yu Luo. Inhibition of Drp1 mitochondrial translocation provides neural protection in dopaminergic system in a Parkinson's disease model induced by MPTP. Scientific Reports. (in press)
2. Xing Guo, Xiaoyan Sun, Di Hu, Yajuan Megan Wang, Hisashi Fujioka, Yu Luo, and Xin Qi. VCP recruitment to mitochondria by mutant Huntingtin causes mitophagy impairment and neurodegeneration in models of Huntington’s disease. Nature Communication (in press)
3. Xiaofei Zhou, Emily Filichia, Brandon Davis, Yu Luo. Effect of the sonic hedgehog receptor smoothened on the survival and function of dopaminergic neurons. Experimental Neurology, 2016 Jun 15;283:235-245.
4. Xin Qi , Brandon Davis, Yung-Hsiao, Chiang, Emily Filichia, Austin Barnett, Nigel Greig, Barry Hoffer, Yu Luo. Dopaminergic neuron-specific deletion of p53 gene is neuroprotective in an experimental Parkinson’s disease model. Journal of Neurochemistry, 2016 Jun 18 (ePub ahead of print)
5. Yang Sheng, Kenzie L. Preston, Paul Tesar, Barry Hoffer, Yu Luo. Using iPSC derived human DA neurons from opioid dependent subjects to study dopamine dynamics. Brain and behaviors 2016; 6(8), e00491 (cover page)
6. JY Wang; YN Huang; C-C Chiu; D Tweedie; W Luo; CG Pick; SY Chou; Y Luo; BJ Hoffer; Nigel Greig; JY Wang. Pomalidomide mitigates neuronal loss, neuroinflammation and behavioral impairments induced by traumatic brain injury in rat. Journal of Neuroinflammation 2016 Jun 28;13(1):168
7. David Tweedie; Koji Fukui; Yazhou Li; Qian-sheng Yu; Shani Barak; Ian A Tamargo; Vardit Rubovitch; Harold W Holloway; Elin Lehrmann; William H Wood III; Yongqing Zhang; Kevin G Becker; Evelyn Perez; Henriette Van Praag; Yu Luo; Barry J Hoffer; Robert E Becker; Chaim G Pick; Nigel H Greig. Cognitive impairments induced by concussive mild traumatic brain injury in mouse are ameliorated by treatment with phenserine via multiple non-cholinergic mechanisms. PLOS One, 2016 Jun 2;11(6):e0156493
8. Sheng, Y., E. Filichia, E. Shick, K. L. Preston, K. A. Phillips, L. Cooperman, Z. Lin, P. Tesar, B. J. Hoffer and Y. Luo " Lower Dopamine D2 Receptor Expression Levels in Human Dopaminergic Neurons Derived From Opioid-Dependent iPSCs." Am J Psychiatry (2016) 173(4): 429-431.
9. Hua-Shan Liu, Hui Shen, Yu Luo, Barry J. Hoffer, Yun Wang, Yihong Yang. Post-treatment with Cocaine- and Amphetamine-regulated Transcript Enhances Infarct Resolution, Reinnervation and Angiogenesis in Stroke Rats - A Magnetic Resonance Imaging Study. NMR in Biomedicine. (2016) 29(3) 361–370.
10. Yu Luo; Alan Hoffer; Barry Hoffer; Xin Qi . Mitochondria: a therapeutic target for Parkinson’s disease? Int. J. Mol. Sci.2015, 16.
11. Emily Filichia, Hui Shen, xiaofei Zhou, Yongmin Jin, Xin Qi, Nigel Greig, Barry Hoffer, Yu Luo. Forebrain neuronal specific ablation of p53 gene provide protection in a cortical ischemic stroke model. Neuroscience. 2015 Jun 4;295:1-10.
12. Yongmin Jin, Nataly Reiv, Austin Barnett, Nicholas Bambakidis, Emily Filichia, Yu Luo. The Shh signaling pathway is upregulated in multiple cell types in cortical ischemia and influences the outcome of stroke in an animal model. PLoS One. 2015; 10(4): e0124657
13. Yu Luo, Hui Shen, Hua, Shan Liu, Seong Jin Yu, David Reiner, Brandon K. Harvey, Barry J. Hoffer, Yihong Yang and Yun Wang. CART peptide induces neuroregeneration in stroke rats. Journal of Cerebral Blood Flow &Metabolism (2013) 33, 300–310
14. Yu Luo, Yun Wang, Serena Y Kuang, Barry Hoffer. Decreased Nurr1 expression level leads to vulnerability to methamphetamine toxicity. 2011, PLoS ONE 5(12): e15193.doi:10.1371/journal.pone.0015193
15. Yu Luo, Goodman CH, Diaz-Ruiz O, Zhang Y, Hoffman AF, Shan L, Kuang SY, Malik N, Chefer VI, Tomac AC, Lupica CR, Bäckman CM. NMDA receptors on non-dopaminergic. neurons in the VTA support cocaine sensitization. PLoS One. 2010 Aug 16;5(8). pii: e12141
16. Yu Luo, Chi-Chung Kuo, Hui Shen, Jenny Chou, Nigel H. Greig, Barry J. Hoffer, Yun Wang, Delayed treatment with a p53 inhibitor enhances functional recovery in stroke brain. Ann Neurol. 2009 May; 65(5):520-530.
17. Yu Luo, Feng Xing, Rita Guiliano, Howard J. Federoff, Identification of a novel Nurr1 interacting protein (2008). J Neurosci. 28(37): 9277-86.
18. Yu Luo, Leigh A. Henricksen, Rita E. Giuliano, Landa Prifti, Linda M. Callahan and Howard J. Federoff (2007). VIP is a transcriptional target of Nurr1 in dopaminergic cells. Experimental Neurology 203(1), 221-232.