About The Luo Lab

"Hotspot" by Preethy Sridharan

"Suspension" by Preethy Sridharan

 

Main Questions

To what extent can the brain naturally repair itself following injury, and what signals regulate this process?

After experiencing a significant amount of damage during injuries such as stroke, the brain makes a valiant effort to repair itself by increasing the proliferation of newborn neurons within its neurogenic niches. However, the majority of these cells die before they are capable of fully maturing and connecting into the surrounding nervous system. We are currently exploring what cells and signals regulate this process to better understand the limits of endogenous repair. 

What can we do to increase the survival and proliferation of newborn and transplanted neurons in neurodegenerative brains? 

Through genetic and pharmacological inhibition of the signals described above, we are finding new ways to promote the survival and proliferation of neurons in the context of neurodegenerative disease. Our long term goal is to develop effective therapies that help slow down or reverse the damage caused by stroke, Parkinson's Disease, 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. Our laboratory utilizes combined strategies such as inducible cell-type specific or activity-dependent 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 Parkinson's Disease

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.

Selected Publications

  1. Turcato FC, Wegman E, Lu T, Ferguson N, Luo Y. Dopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons. iScience. 2022 Oct 7;25(11):105278. doi: 10.1016/j.isci.2022.105278. PMCID: PMC9587326.

  2. Fucheng Luo, Jiapeng Wang, Zhen Zhang, Zhen You, Alicia Bedolla, FearGod Okwubido-Williams, L. Frank Huang, Jerry Silver, Yu Luo. Inhibition of CSPG receptor PTPσ promotes migration of newly born neuroblasts, axonal sprouting, and recovery from stroke. Cell Reports. 40(4) July, 2022. https://doi.org/10.1016/j.celrep.2022.111137

  3. Ware K, Wegman E, Bedolla A, Luo Y. Major Caveats Discovered in the Genetic Cell Ablation Model Used to Study Microglia Functions. Transl. Stroke Res. 2022. https://doi.org/10.1007/s12975-022-01029-0

  4. Wang J, Ware K, Bedolla A, Allgire E, Turcato F, Weed M, Sah R, Luo Y. Disruption of Sonic Hedgehog Signaling Accelerates Age-Related Neurogenesis Decline and Abolishes Stroke-Induced Neurogenesis and Leads to Increased Anxiety Behavior in Stroke Mice. Transl. Stroke Res. 2022 Jan 31. https://doi.org/10.1007/s12975-022-00994-w

  5. Bedolla A, Taranov A, Luo F, Wang J, Turcato F, Fugate EM, Greig NH, Lindquist DM, Crone SA, Goto J, Luo Y. Diphtheria toxin induced but not CSF1R inhibitor mediated microglia ablation model leads to the loss of CSF/ventricular spaces in vivo that is independent of cytokine upregulation. J Neuroinflammation. 2022 Jan 4;19(1):3. doi: 10.1186/s12974-021-02367-w. PubMed PMID: 34983562; PubMed Central PMCID: PMC8728932.

  6. Boyne P, Awosika OO, Luo Y. Mapping the corticoreticular pathway from cortex-wide anterograde axonal tracing in the mouse. J Neurosci Res. 2021 Dec;99(12):3392-3405. doi: 10.1002/jnr.24975. Epub 2021 Oct 22. PubMed PMID: 34676909; PubMed Central PMCID: PMC8714061.

  7. Luo F, Zhang Z, Luo Y. Differential Role of p53 in Oligodendrocyte Survival in Response to Various Stresses: Experimental Autoimmune Encephalomyelitis, Cuprizone Intoxication or White Matter Stroke. Int J Mol Sci. 2021 Nov 26;22(23). doi: 10.3390/ijms222312811. PubMed PMID: 34884611; PubMed Central PMCID: PMC8658009.

  8. Gu Y, Gao H, Kim K, Liu Y, Ramos-Estebanez C, Luo Y, Wang Y, Yu X. Dynamic oxygen-17 MRI with adaptive temporal resolution using golden-means-based 3D radial sampling. Magn Reson Med. 2021 Jun;85(6):3112-3124. doi: 10.1002/mrm.28636. Epub 2020 Dec 25. PubMed PMID: 33368649; PubMed Central PMCID: PMC8324328.

  9. Luo F, Zhang Z, Barnett A, Bellinger TJ, Turcato F, Schmidt K, Luo Y. Cuprizone-induced demyelination under physiological and post-stroke condition leads to decreased neurogenesis response in adult mouse brain. Exp Neurol. 2020 Apr;326:113168. doi: 10.1016/j.expneurol.2019.113168. Epub 2020 Jan 2. Review. PubMed PMID: 31904386.

  10. Hu D, Sun X, Liao X, Zhang X, Zarabi S, Schimmer A, Hong Y, Ford C, Luo Y, Qi X. Alpha-synuclein suppresses mitochondrial protease ClpP to trigger mitochondrial oxidative damage and neurotoxicity. Acta Neuropathol. 2019 Jun;137(6):939-960. doi: 10.1007/s00401-019-01993-2. Epub 2019 Mar 15. PubMed PMID: 30877431; PubMed Central PMCID: PMC6531426.

  11. Glotfelty EJ, Delgado T, Tovar-Y-Romo LB, Luo Y, Hoffer B, Olson L, Karlsson T, Mattson MP, Harvey B, Tweedie D, Li Y, Greig NH. Incretin Mimetics as Rational Candidates for the Treatment of Traumatic Brain Injury. ACS Pharmacol Transl Sci. 2019 Apr 12;2(2):66-91. doi: 10.1021/acsptsci.9b00003. Epub 2019 Feb 11. PubMed PMID: 31396586; PubMed Central PMCID: PMC6687335.

  12. Hsueh, Shih-Chang; Chen, Kai-Yun; Lai, Jing-Huei; Wu, Chung-Che; Yu, Yu-Wen; Luo, Yu; Hsieh, Tsung-Hsun; Chiang, Yung-Hsiao (2018. ) Voluntary Physical Exercise Improves Subsequent Motor and Cognitive Impairments in a Rat Model of Parkinson's Disease.International journal of molecular sciences, , 19 (2 )

  13. Kim, Dong Seok; Choi, Ho-Il; Wang, Yun; Luo, Yu; Hoffer, Barry J; Greig, Nigel H (2017. ) A New Treatment Strategy for Parkinson's Disease through the Gut-Brain Axis: The Glucagon-Like Peptide-1 Receptor Pathway.Cell transplantation, , 26 (9 ) ,1560-1571More Information

  14. Lu, Tao; Kim, Paul P; Greig, Nigel H; Luo, Yu (2017. ) Dopaminergic Neuron-Specific Deletion of p53 Gene Attenuates Methamphetamine Neurotoxicity.Neurotoxicity research, , 32 (2 ) ,218-230More Information

  15. Jin, Yongming; Barnett, Austin; Zhang, Yifan; Yu, Xin; Luo, Yu (2017. ) Poststroke Sonic Hedgehog Agonist Treatment Improves Functional Recovery by Enhancing Neurogenesis and Angiogenesis.Stroke, , 48 (6 ) ,1636-1645More Information

  16. Yang, Ling-Yu; Greig, Nigel H; Huang, Ya-Ni; Hsieh, Tsung-Hsun; Tweedie, David; Yu, Qian-Sheng; Hoffer, Barry J; Luo, Yu; Kao, Yu-Chieh; Wang, Jia-Yi (2016. ) Post-traumatic administration of the p53 inactivator pifithrin-O oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury.Neurobiology of disease, , 96 ,216-226More Information

  17. Filichia, Emily; Hoffer, Barry; Qi, Xin; Luo, Yu (2016. ) Inhibition of Drp1 mitochondrial translocation provides neural protection in dopaminergic system in a Parkinson's disease model induced by MPTP.Scientific reports, , 6 ,32656More Information

  18. Zhou, Xiaofei; Pace, Jonathan; Filichia, Emily; Lv, Tao; Davis, Brandon; Hoffer, Barry; Selman, Warren; Luo, Yu (2016. ) Effect of the sonic hedgehog receptor smoothened on the survival and function of dopaminergic neurons.Experimental neurology, , 283 (Pt A ) ,235-45More Information

  19. Qi, Xin; Davis, Brandon; Chiang, Yung-Hsiao; Filichia, Emily; Barnett, Austin; Greig, Nigel H; Hoffer, Barry; Luo, Yu (2016. ) Dopaminergic neuron-specific deletion of p53 gene is neuroprotective in an experimental Parkinson's disease model.Journal of neurochemistry, , 138 (5 ) ,746-57More Information

  20. Guo, Xing; Sun, XiaoYan; Hu, Di; Wang, Ya-Juan; Fujioka, Hisashi; Vyas, Rajan; Chakrapani, Sudha; Joshi, Amit Umesh; Luo, Yu; Mochly-Rosen, Daria; Qi, Xin (2016. ) VCP recruitment to mitochondria causes mitophagy impairment and neurodegeneration in models of Huntington's disease.Nature communications, , 7 ,12646More Information

  21. Wang, Jin-Ya; Huang, Ya-Ni; Chiu, Chong-Chi; Tweedie, David; Luo, Weiming; Pick, Chaim G; Chou, Szu-Yi; Luo, Yu; Hoffer, Barry J; Greig, Nigel H; Wang, Jia-Yi (2016. ) Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral impairments induced by traumatic brain injury in rat.Journal of neuroinflammation, , 13 (1 ) ,168More Information

  22. Sheng, Yang; Filichia, Emily; Shick, Elizabeth; Preston, Kenzie L; Phillips, Karran A; Cooperman, Leslie; Lin, Zhicheng; Tesar, Paul; Hoffer, Barry; Luo, Yu (2016. ) Using iPSC-derived human DA neurons from opioid-dependent subjects to study dopamine dynamics.Brain and behavior, , 6 (8 ) ,e00491More Information

  23. Sheng, Yang; Filichia, Emily; Shick, Elizabeth; Preston, Kenzie L; Phillips, Karran A; Cooperman, Leslie; Lin, Zhicheng; Tesar, Paul; Hoffer, Barry J; Luo, Yu (2016. ) Lower Dopamine D2 Receptor Expression Levels in Human Dopaminergic Neurons Derived From Opioid-Dependent iPSCs.The American journal of psychiatry, , 173 (4 ) ,429-31More Information

  24. Liu, H-S; Shen, H; Luo, Y; Hoffer, B J; Wang, Y; Yang, Y (2016. ) Post-treatment with cocaine- and amphetamine-regulated transcript enhances infarct resolution, reinnervation, and angiogenesis in stroke rats - an MRI study.NMR in biomedicine, , 29 (3 ) ,361-70More Information

  25. Luo, Yu; Hoffer, Alan; Hoffer, Barry; Qi, Xin (2015. ) Mitochondria: A Therapeutic Target for Parkinson's Disease?.International journal of molecular sciences, , 16 (9 ) ,20704-30More Information

  26. Yu Luo, Hui Shen, Hua‐Shan Liu, Seong‐Jin Yu, David Reiner, Brandon K. Harvey, Barry J. Hoffer, Yihong Yang, and Yun Wang (2013. ) CART peptide induces neuroregeneration in stroke rats .Journal of Cerebral Blood Flow and Metabolism , , 33 (2 ) ,300-10

  27. Filichia, E; Shen, H; Zhou, X; Qi, X; Jin, K; Greig, N; Hoffer, B; Luo, Y (2015. ) Forebrain neuronal specific ablation of p53 gene provides protection in a cortical ischemic stroke model.Neuroscience, , 295 ,1-10More Information

  28. Yu Luo, Chi-Chung Kuo, Hui Shen, Jenny Chou, Nigel H. Greig, Barry J. Hoffer, Yun Wang (2009. ) Delayed treatment with a p53 inhibitor enhances functional recovery in stroke brain .Ann Neurol, , 65 (5 ) ,520-30

  29. Jin, Yongmin; Raviv, Nataly; Barnett, Austin; Bambakidis, Nicholas C; Filichia, Emily; Luo, Yu (2015. ) 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, , 10 (4 ) ,e0124657More Information

  30. Yu Luo, Feng Xing, Rita Guiliano, Howard J. Federoff (2008. ) Identification of a novel Nurr1 interacting protein .J Neurosci, , 28 (37 ) , 9277-86

  31. 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

  32. Gu, Yuning; Gao, Huiyun; Kim, Kihwan; Liu, Yuchi; Ramos-Estebanez, Ciro; Luo, Yu; Wang, Yunmei; Yu, Xin (2021. ) Dynamic oxygen-17 MRI with adaptive temporal resolution using golden-means-based 3D radial sampling.Magnetic resonance in medicine, , 85 (6 ) ,3112-3124More Information

  33. Luo, Fucheng; Zhang, Zhen; Barnett, Austin; Bellinger, Tania J; Turcato, Flavia; Schmidt, Kelly; Luo, Yu (2020. ) Cuprizone-induced demyelination under physiological and post-stroke condition leads to decreased neurogenesis response in adult mouse brain.Experimental neurology, , 326 ,113168More Information

  34. Flavia Turcato, Paul Kim, Austin Barnett, Yongming Jin, Mike Scerba, Anthony Casey, Warren Selman, Nigel H. Greig, and Yu Luo (2018. ) Sequential combined Treatment of Pifithrin-α and Posiphen Enhances Neurogenesis and Functional Recovery After Stroke .Cell Transplantation, ,

  35. Hu, Di; Sun, Xiaoyan; Liao, Xudong; Zhang, Xinwen; Zarabi, Sara; Schimmer, Aaron; Hong, Yuning; Ford, Christopher; Luo, Yu; Qi, Xin (2019. ) Alpha-synuclein suppresses mitochondrial protease ClpP to trigger mitochondrial oxidative damage and neurotoxicity.Acta neuropathologica, , 137 (6 ) ,939-960More Information

  36. Glotfelty, Elliot J; Delgado, Thomas; Tovar-Y-Romo, Luis B; Luo, Yu; Hoffer, Barry; Olson, Lars; Karlsson, Tobias; Mattson, Mark P; Harvey, Brandon; Tweedie, David; Li, Yazhou; Greig, Nigel H (2019. ) Incretin Mimetics as Rational Candidates for the Treatment of Traumatic Brain Injury.ACS pharmacology & translational science, , 2 (2 ) ,66-91More Information

  37. Turcato, Flavia; Kim, Paul; Barnett, Austin; Jin, Yongming; Scerba, Mike; Casey, Anthony; Selman, Warren; Greig, Nigel H; Luo, Yu (2018. ) Sequential combined Treatment of Pifithrin-? and Posiphen Enhances Neurogenesis and Functional Recovery After Stroke.Cell transplantation, , 27 (4 ) ,607-621More Information

  38. Chang, Cheng-Fu; Lai, Jing-Huei; Wu, John Chung-Che; Greig, Nigel H; Becker, Robert E; Luo, Yu; Chen, Yen-Hua; Kang, Shuo-Jhen; Chiang, Yung-Hsiao; Chen, Kai-Yun (2017. ) (-)-Phenserine inhibits neuronal apoptosis following ischemia/reperfusion injury.Brain research, , 1677 ,118-128More Information

  39. Lu, Tao; Kim, Paul; Luo, Yu (2017. ) Tp53 gene mediates distinct dopaminergic neuronal damage in different dopaminergic neurotoxicant models.Neural regeneration research, , 12 (9 ) ,1413-1417More Information

  40. Xu, Kui; Ye, Lena; Sharma, Katyayini; Jin, Yongming; Harrison, Matthew M; Caldwell, Tylor; Berthiaume, Jessica M; Luo, Yu; LaManna, Joseph C; Puchowicz, Michelle A (2017. ) Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse.Advances in experimental medicine and biology, , 977 ,205-213More Information

  41. Wang, Jing-Ya; Huang, Ya-Ni; Chiu, Chong-Chi; Tweedie, David; Luo, Weiming; Pick, Chaim G; Chou, Szu-Yi; Luo, Yu; Hoffer, Barry J; Greig, Nigel H; Wang, Jia-Yi (2016. ) Erratum to: Pomalidomide mitigates neuronal loss, neuroinflammation, and behavioral impairments induced by traumatic brain injury in rat.Journal of neuroinflammation, , 13 (1 ) ,228More Information

  42. Tweedie, David; Fukui, Koji; Li, Yazhou; Yu, Qian-Sheng; Barak, Shani; Tamargo, Ian A; Rubovitch, Vardit; Holloway, Harold W; Lehrmann, Elin; Wood, William H; Zhang, Yongqing; Becker, Kevin G; Perez, Evelyn; Van Praag, Henriette; Luo, Yu; Hoffer, Barry J; Becker, Robert E; Pick, Chaim G; Greig, Nigel H (2016. ) Cognitive Impairments Induced by Concussive Mild Traumatic Brain Injury in Mouse Are Ameliorated by Treatment with Phenserine via Multiple Non-Cholinergic and Cholinergic Mechanisms.PloS one, , 11 (6 ) ,e0156493More Information

  43. Luo, Yu (2012. ) The function and mechanisms of Nurr1 action in midbrain dopaminergic neurons, from development and maintenance to survival.International review of neurobiology, , 102 ,1-22More Information

  44. Luo, Y; Neet, K E (1992. ) The unprocessed C-terminal dipeptide of recombinant beta-nerve growth factor determines three stable forms with distinct biological activities. The Journal of biological chemistry, , 267 (17 ) ,12275-83