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Center for Advanced Therapeutic Strategies for Brain Disorders (CATSBD)

The Center for Advanced Therapeutic Strategies for Brain Disorders (CATSBD) at Roskamp Institute headed by Dr. Yong Shen is devoted to combining baic research on mechanisms of cognition and neuron functions in the healthy brain with brain disorders. Our discoveries are laying the foundation for better understanding and treatments of various brain disorders, including Alzheimer's disease, Parkinson's disease, stroke, ALS (Lou Gehring's disease), multiple scleorosis, and schizophrenia. The translational research approaches take advantages of the basic science discoveries in brain disorders to translate advances in the laboratories efficiently and rapidly into diagnosis, technologies and therapies for patients, their families, their friends and their communities.

The mission of the CATSBD is to promote and accelerate the transfer of basic science discoveries to clinical medical practice. The CATSBD creates and supports multidisciplinary programs that help bring the discoveries of the laboratory to clinical applications, offering a unique training ground for pre- or/and medical students and post-doctoral/medical fellows. It provides support for the following research programs in the CATSBD at the Roskamp Institute:

  • Investigation of cell process underlying neuron death or dysfunctions using cell culture and animal models.

  • Elucidation of new molecular pathways of neurodegeneration and neuron survival and discovery of novel therapies.

  • Molecular dissection of inflammatory elements that affect neurodegeneration or survival.

  • Identification of biomarkers for early diagnosis of the brain disorders and monitoring efficacy of the clinical trials.

  • Identification of new genes for the brain disorders.

  • Examination of new technologies for fostering understanding adult stem cells as a potential treatment of the brain disorders.

  • Developing new bio-assay systems to effectively screen potential drugs, including small molecule chemical compounds as well as herbal medicines.

  • Clinical trials to treat the brain disorders.



For open positions at this center please visit our careers website.


Selected publications:

In Alzheimer's Disease Research:

  1. Yang, L.B. R. Li, Rogers, J , Meri, S. and Shen, Y. (2000) Deficiency of CD59, complement defense protein, in the Alzheimer' brain may contribute to neurodegeneration. Journal of Neuroscience, 20(20): 7505-7509.

  2. Lue, L-F. Rydel, R., Brigham, Yang, L-B., Hampel, H., Murphy, GM. Jr., Brochova, L., Yan, SD., Walker DG., Shen, Y. and Rogers (2001) Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro.  Glia, 35(1), 72-79.

  3. Yang, L. B., Lindholm, K., Konishi, Y. Li, R. and Shen Y (2002) Target deletion of distinct TNF receptor subtypes reveals hippocampal neuron death and survival through different signal transduction pathways.  Journal of Neuroscience, 22(8), 3025- 3032.

  4. Konishi, Y., Yang, L-B. Lindholm, and Shen, Y. (2002) Molecular isolation of living neurons from human elderly brains by using the immunomagentic sorting DNA-linker sytem. American Journal of Pathology. 161(5), 1567-1576.

  5. Hampel, H., Teipel, SJ., Fuchsberger, T., Andreasen, N., Wiltfang, J., Otto, M., Shen, Y., Dodel, D., Y Du, Y. Farlow, M., Mo, H-J., K Blennow, K. and Buerger, K. (2004). Value of CSF b-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment. Molecular Psychiatry, 111(3):247-72.

  6. Yang, L-B., Yan, R., Citron, M., Xia, W-M, Yang, X-L, Wong, P., Price, D., Li, R.. and Shen. Y. (2003) Elevated beta secretase expression and enzymatic activity detected in sporadic Alzheimer's disease brains.  Nature Medicine, 9(1), 3-4.

  7. Li R., Yang LB, Lindholm K, Yan R, Citron M, Beach T, Sue L, Subbagh M., Cai H., Wong P, Price D, Shen Y. (2004). Aß load is correlated with elevated BACE activity in sporadic Alzheimer patients. Proceedings of National Academy of Science, USA (PNAS). 101, 3632-3637.

  8. Li R., Lindholm K, Yang LB, Konishi Y, Hampel H, Zhang, D. Shen Y. (2004). TNF death receptor signaling cascade is required for amyloid-b-protein induced neuron death. Journal of Neuroscience, 28(7):1760-1771.

  9. Yue X, Lu M, Lancaster T, Cao P, Honda S, Staufenbiel M, Harada N, Zhong Z, Shen Y, Li R. (2005). Brain estrogen deficiency accelerates A-beta plaque formation in an Alzheimer's disease animal model. Proceedings of National Academy of Science, USA (PNAS). 102(52):19198-203.

  10. Tesco G, Koh YH, Kang EL, Cameron AN, Das S, Sena-Esteves M, Hiltunen M, Yang SH, Zhong Z, Shen Y, Simpkins JW, Tanzi RE. (2007). Depletion of GGA3 stabilizes BACE and enhances beta-secretase activity. Neuron. 54(5):721-3.

  11. He P, Zhong Z, Lindholm K, Berning L, Lee W, Lemere C, Staufenbiel S, Li R and Shen, Y. (2007). Deletion of TNFR death receptor inhibits amyloid protein production and prevents learning and memory deficits in Alzheimer's transgenic mice. Journal of Cell Biology, 178(5): 829-841.

  12. He, P. and Shen, Y. (2009). Interruption of b-catenin signaling reduces neurogenesis in Alzheimer's disease's brains. Journal of Neuroscience,29(20):6545-57.

  13. Ghosal P., Vogt D, Man L, Shen Y, Lamb B., Pimplikar, SW (2009). Alzheimer's disease-like pathological features in transgenic mice expressing the APP intracellular domain. Proceedings of National Academy of Science, U S A (PNAS), 106(43): 18367-18377.

  14. Cheng X, Yang L, He P, Li R, Shen Y. (2010). Differential activation of tumor necrosis factor receptors distinguishes between brains from Alzheimer's disease and non-demented patients. Journal of Alzheimer's Disease. 19(2):621-30.

  15. Furuya T., Kim M., Lipinski M., Li J., Kim D., Lu T., Shen, Y., Rameh L., Yankner B., Tsai LH and Yuan J. (2010). Negative regulation of Vps34 by Cdk mediated phosphorylation. Cell Molecular Cell, 38(4):500-11.

  16. McAllister C, Long J, Bowers A, Walker A, Cao P, Honda S, Harada N, Staufenbiel M, Shen Y, Li R. (2010). Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment. Journal of Neuroscience, 30(21):7326-34.

  17. Min S-W, Cho S-H, Zhou Y, Schroeder S, Haroutunian V, Seeley WW, Huang EJ, Shen Y, Masliah E, Mukherjee C, Meyers D, Cole PA, Ott M, Li Gan L (2010). Acetylation of tau inhibits Its degradation and contributes to tauopathy. Neuron, 67: 953-966.

  18. Yang J, Han H, Chui D, Shen Y and Wu J (2011). Prominent activation of the intraparietal and somatosensory areas during angle discrimination by intra-active touch. Human Brain Mapping, 33:2957-2970.

  19. He P, Liu Q, Wu J and Shen Y (2011). Genetic deletion of TNF receptor suppresses excitatory synaptic transmission via reducing AMPA receptor synaptic localization in cortical neurons. FASEB Journal. 26(1): 334-45.

  20. Long J, He P, Shen Y, Li R. (2012). New evidence of mitochondria dysfunction in the female Alzheimer's disease brain: deficiency of estrogen receptor-ß. Journal of Alzheimer's Disease. 30(3): 545-58.

  21. Walker KR, Kang EL, Whalen MJ, Shen Y and Tesco G. (2012). Depletion of GGA1 and GGA3 mediates post-injury elevation of BACE1. Journal of Neuroscience. 32(30): 10423-37.

  22. Li R, Cui J, He P, Staufenbiel M, Harada N, Shen Y (2012). Brain endogenous estrogen levels determine responses to estrogen replacement therapy via regulation of BACE1 and NEP in female Alzheimer's transgenic mice. Molecular Neurobiology, Nov. 20.

 

In Parkinson's Disease research: 

  1. Jiang H, He P, Adler CH, Shill H, Beach TG, Li, R, and Shen Y. (2012). Bid signal pathway components are identified in the temporal cortex in brains with Parkinson's disease. Neurology, 79(17):1767-73.

  2. Cho HJ, Jin SM, Ding J, Xie C, Yu J, Parisiadou L, Sun L, Vancraenenbroeck R, Lobbestael E, Baekelandt V, Taymans J-M, He P, Troncoso J, Shen Y, Cai H (2013). MicroRNA-205 regulates the Expression of Parkinson's disease-related Leucine-rich Repeat Kinase 2 Protein. Human Molecular Genetics, Feb 1; 22(3):608-20. Epub 2012 Nov 2.

  3. Yu X, Du T, Song N, He Q, Shen Y, Jiang H, and Xie J (2013). Decreased iron levels in the temporal cortex in postmortem human brains with Parkinson's disease. Neurology, Jan. 29; 80(5): 492-495. 

 

Biomarkers for early diagnosis of neurodegenerative disorders, AD and PD:

  1. Hampel, H., Teipel, SJ., Fuchsberger, T., Andreasen, N., Wiltfang, J., Otto, M., Shen, Y., Dodel, D., Y Du, Y. Farlow, M., Mo, H-J., K Blennow, K. and Buerger, K. (2004). Value of CSF ß-amyloid1-42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment. Molecular Psychiatry, 111(3):247-72.

  2. Büerger K, Teipel SJ, Zinkowski R, Sunderland T, Andreasen N, Blennow K, Ewers M, DeBernardis J, Shen Y, Hampel H. (2005). Increased levels of CSF phosphorylated tau in apolipoprotein E epsilon4 carriers with mild cognitive impairment. Neuroscience Letters. 391(1-2):48-50.

  3. Zhong Z, Ewers M, Teipel S, Büerger K, Wallin A, Blennow K, He P, McAllister C, Hampel H, Shen Y (2007). High Levels of Beta-Secretase (BACE1) in Cerebrospinal Fluid as a Predictor of Risk in Mild Cognitive Impairment, the early stage of Alzheimer's Disease, Archives of General Psychiatry, 64(6):718-2.

  4. Ewers M, Zhong Z, Büerger K, Wallin A, Blennow K, Teipel SJ, Shen Y, Hampel H. (2008). Increased CSF-BACE 1 activity is associated with ApoE-e4 genotype in subjects with mild cognitive impairment (MCI) and Alzheimer's disease. Brain, 131(Pt 5):1252-8.

  5. Xia W., Yang T., Imelda M. Smith I. M., Shen Y., Walsh D. M. and Dennis J. Selkoe, D. J. (2008). A specific ELISA for measuring amyloid b-protein oligomers in human plasma and the brains of Alzheimer patients. Archives of Neurology, 66(2):190-9.

  6. Sabbagh MN, Nural H, He P, Sirrel S, Belden C, Liebsack C, Li R, Shen Y. (2010). Rationale and strategy for thalidomide as a BACE1 inhibitor for a phase II randomized clinical trial in mild-to-moderate Alzheimer's disease. Alzheimers Dementia 6(4): 19: 621-630. 0

  7. Ewers M, Cheng X, Nural HF, Walsh C, Meindl T, Teipel SJ, Buerger K, Shen Y, Hampel H. (2010). CSF- BACE1 activity predicts hippocampus atrophy in Alzheimer's disease. Journal of Alzheimer's Disease, 25(2):373-81.

  8. Jiang H, Hampel H, Prvulovic D, Wallins A, Blennow K, Li R, and Shen Y (2011). Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer's disease. Molecular Neurodegeneration. Oct. 6; 61(1):69.

  9. Wu J, Yang J, Yu, Y, Li Q, Nakamura N, Shen Y, Ohta Y, Yu, S, and Abe K (2012). Delayed audiovisual integration of patients with mild cognitive impairment and Alzheimer's disease compared with normal aged Controls. Journal of Alzheimer's Disease. 32: 317-328.

  10. Bai L, Song N, Yu J, Tan L, Shen Y, Xie J, Jiang H. (2013). Elevated Plasma Levels of Soluble TNFRs and TACE Activity in Alzheimer's Disease Patients of Northern Han Chinese Descent. Current Alzheimer Research 10(1):57-62.

In Drug Discovery:

  1. Chirapu, S. R, Pachaiyappan, B, Zhong, Z., Abdul-Hay, S. O., Yuan, H., Thatcher, G., Shen, Y., Kozikowski, A. P, Petukhov, P. A. (2008). Molecular modeling, Synthesis and Activity Studies of Inhibitors Targeting Alzheimer's disease β-Secretase (BACE1). Biological Medicinal Chemistry Letters, 19(1): 264-74. 

  2. Kozikowski, A. P., Chen, Y., Subahasish, T., Zhong, Z., Melissa A. D'Annibale, M.A., Shen, Y. and Langley, B.C. (2009). Searching for Disease Modifiers-PKC Activation and HDAC Inhibition-A Dual Drug Approach to Alzheimer's Disease that Decreases Aß Production while Blocking Oxidative Stress. ChemMedChem. 4(7):1095-105. 

  3. Hua Q, Xiaolei Zhu X, Li P, Tang H, Cai D, Xu Y, Jia X, Chen J, and Shen Y (2008). Refined Qing Kai Ling, traditional Chinese medicinal preparation, reduces ischemic stroke-induced infarct size and neurological deficits and increases expression of endothelial nitric oxide synthase. Biol. Pharm. Bull. 31(4):633-637.

  4. He P, Cheng X, Staufenbiel M, Li R and Shen Y (2013). Long-term treatment of thalidomide ameliorates Alzheimer-like pathology through inhibition of β-secretase in a mouse model of Alzheimer's disease. PLoS One, Feb.6, 8(2): e55091.

  5. He P, Li P, Hua Q, Liu Y, Staufenbiel M, Li R, and Shen Y (2013). Chronic administration of anti-stroke herbal medicine TongLuoJiuNao reduces abnormal processing of amyloid precursor protein in a mouse model of Alzheimer's Disease. PLoS One, March 5.

Perspective and review articles and chapters/books:

  1. Sibley, D. R., Monsma, Jr., F.J. and Shen, Y.   (1993) Molecular neurobiology of D1 and D2 dopamine receptors.   In Neuroscience Perspectives, D1:D2 Dopamine Receptors Interactions: Neuroscience and Psychopharmacology (ed).   P. G. Jenner and J. L. Waddington, Academic Press.

  2. Sibley, D. R., Monsma, Jr., F.J. and Shen, Y.   (1993) Molecular neurobiology of dopaminergic receptors.   International Review of Neurobiology, 35: 391-415.

  3. Shen, Y., Li, R., Specht, S. M. and S. Ghislain (1994). The hippocampus: a biological model for studying learning and memory.  Invited review, Progress in Neurobiology, 44: 485-496.

  4. Shen, Y. and Li, R. (1995) The role of endogenous neuropeptides in learning and memory and possible mechanisms.  Invited review, Journal of Medical Hypothesis. 45:529-538.

  5. Rogers, J. and Shen, Y. (2000) Organization of inflammatory processes in Alzheimer's disease.  In: Neuro-Immune Interactions in Neurologic and Psychiatric Disorders. By Patterson P., Kordon, C. and Christen Y. (Eds). Foundation IPSEN, Research and Perspectives in Neuroscience.

  6. Rogers, J., Yang, L-B., Lue, L-F, Strohmeyer R., Liang, Z., Konishi, K., Li, R., Walker, D. and Shen Y.  (2000). Inflammatory mediators in the Alzheimer's disease brain.  NeuroScience News, 3(4), 38-45.

  7. Rogers, J. and Shen, Y. (2000) A perspective on inflammation in Alzheimer's disease.  Annals of New York  Acad.  Sci. 924: 132-135.

  8. Shen, Y. and Seppo M. (2003) Yin and Yang: Roles of Complement and its regulation in Alzheimer's disease. Progress in Neurobiology, 70(6):463-72.

  9. Li R and Shen Y. (2005). Estrogen and brain: synthesis, function and diseases. Front Biosci. 10:257-67.

  10. Shen Y, He P, Zhong Z, McAllister C, Lindholm K. (2006). Distinct destructive signal pathways of neuronal death in Alzheimer's disease. Trends in Molecular Medicine. 12(12):574-9.

  11. Hampel H and Shen Y. (2009). BACE1 as a biological candidate marker of Alzheimer's disease. Scand J Clin Lab Invest. 69(1):8-12.

  12. Hampel H, Shen Y, Walsh DM, Aisen P, Shaw LM, Zetterberg H, Trojanowski JQ, Blennow K. (2009). Biological markers of amyloid beta-related mechanisms in Alzheimer's disease. Experimental Neurology. Oct 6.

  13. Cui J, Shen Y and Li R (2013). Tissue and cell-specific estrogen synthesis and signaling pathways during ageing: from peripheral to brain. Trends in Molecular Medicine. Jan. 21. doi:pii: S1471-4914(12)00244-4.

  14. Li R, Cui J, Jothishankar B, Shen J, He P, Shen Y. (2012). Early reproductive experiences in females make differences in cognitive function later in life. Journal of Alzheimer's Disease (JAD). Dec. 27.

  15. Wang H, Li, R and Shen Y (2013).  ß-secretase: Its Biology as a Therapeutic Target in Diseases. Trends in Pharmacological Sciences. April.


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"We have assembled a fantastic team of scientists and clinicians here at the Roskamp Institute." – Dr. Fiona Crawford