There are two main areas of research in my laboratory. The first one concerns the study of the nature of the so-called neuronal cell cycle. Differentiated neurons display specific biochemical, physiological and morphological properties that apparently prevent them from further cell division. Nevertheless, expression of cell cycle modulators persists after neuronal differentiation and is upregulated under stress conditions, such as trophic factor deprivation, oxidative stress and the presence of DNA damaging agents. This apparent reactivation of the cell cycle has been postulated as a sine qua non for neuronal death in response to those stress conditions, particularly in Alzheimer’s disease. My laboratory is currently addressing the impact of different molecular players in the generation and progression of what we currently define as the neuronal cell cycle, using a variety of transgenic mouse models.
The second area of research in which I am interested concerns the functional link between amyloid and tau in the generation of neurodegenerative mechanisms. According to the amyloid hypothesis of neurodegeneration in Alzheimer’s disease (AD), an excess of amyloid in the AD brain leads to neuronal death through a mechanism involving aberrant tau phosphorylation. In my laboratory, we are interested in unveiling the basic molecular mechanisms behind the impact of APP and tau on neurodegeneration. To that end, we are currently using a mouse model that recapitulates faithfully the aberrant molecular phenotype of amyloid accumulation and tau hyperphosphorylation present in AD.
1. Castello MA, Soriano S. (2012). Rational heterodoxy: cholesterol reformation of the amyloid doctrine. Ageing Res Rev. In press
2. Ana Nunes, Sarah NR Pressey, Jonathan D Cooper, Soriano S. (2011). Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis. Neurobiol Dis. 42:349-59
3. Canuet L, Ishii R, Iwase M, Ikezawa K, Kurimoto R, Takahashi H, Currais A, Azechi M, Aoki Y, Nakahachi T, Soriano S, Takeda M. (2011). Psychopathology and working memory-induced activation of the prefrontal cortex in schizophrenia-like psychosis of epilepsy: Evidence from magnetoencephalography. Psychiatry Clin Neurosci. 65:183-90
4. Engmann O, Hortobágyi T, Thompson AJ, Guadagno J, Troakes C, Soriano S, Al-Sarraj S, Kim Y, Giese KP. (2011). Cyclin-dependent kinase 5 activator p25 is generated during memory formation and is reduced at an early stage in Alzheimer's disease. Biol Psychiatry 70:159-68.
5. Hayashi N, Kazui H, Kamino K, Tokunaga H, Takaya M, Yokokoji M, Kimura R, Kito Y, Wada T, Nomura K, Sugiyama H, Yamamoto D, Yoshida T, Currais A, Soriano S, Hamasaki T, Yamamoto M, Yasuda Y, Hashimoto R, Tanimukai H, Tagami S, Okochi M, Tanaka T, Kudo T, Morihara T, Takeda M. (2010). KIBRA Genetic Polymorphism Influences Episodic Memory in Alzheimer’s Disease, but Does Not Show Association with Disease in a Japanese Cohort. Dement Geriatr Cogn Disord In press.
6. Currais A, Kato K, Canuet L, Ishii R, Tanaka T, Takeda M, Soriano S. (2010). Caffeine modulates tau phosphorylation and affects Akt signaling in postmitotic neurons. J Mol Neurosci In press
7. Skerget K, Taler-Vercic A, Bavdek A, Hodnik V, Ceru S, Tusek-Znidaric M, Kumm T, Pitsi D, Pompe-Novak M, Palumaa P, Soriano S, Kopitar-Jerala N, Turk V, Anderluh G, Zerovnik E. (2010). Interaction between oligomers of stefin B and amyloid-beta in vitro and in cells. J Biol Chem 285: 3201-10
8. Currais A, Hortobagyi T, Soriano S (2009). The neuronal cell cycle as a mechanism of pathogenesis in Alzheimer’s disease. Aging. 1:363-71
9. Nunes A, Ohadi M, Rahimi A, Aghajani A, Najmabadi H, Currais A, Soriano S. (2008). A mutation in the calreticulin gene promoter in a family case of schizoaffective disorder leads to its aberrant transcriptional activation. Brain Research. 1239: 36-41
10. Malik B, Currais A, Soriano S. (2008). Cell cycle-driven neuronal apoptosis specifically linked to amyloid peptide Abeta1-42 exposure is not exacerbated in a mouse model of presenilin-1 familial Alzheimer's disease. J. Neurochem. 106(2):912-6
11. Malik B, Currais A, Andres A, Towlson C, Pitsi D, Nunes A, Niblock M, Cooper J, Hortobágyi T, Soriano S. (2008). Loss of neuronal cell cycle control as a mechanism of neurodegeneration in the presenilin-1 Alzheimer's disease brain. Cell Cycle. 7(5):637-46.
12. Chevallier, NL, Soriano, S, Kang, DE, Masliah, E, Hu, G, and Koo, EH. (2005). Perturbed neurogenesis in the adult hippocampus associated with presenilin-1 A246E mutation. Am. J. Pathol. 2005 167:151-9.
13. Lu, D., Soriano, S. Bredesen, D., Koo, EH. (2003). Caspase cleavage of the amyloid precursor protein modulates amyloid beta-protein toxicity J Neurochem. Nov; 87(3):733-41.
14. Kang D, Soriano S, Xia X, Eberhart C, De Strooper B, Zheng H, Koo E (2002). Presenilin Couples the Paired Phosphorylation of β-Catenin Independent of Axin. Implications for β-Catenin Activation in Tumorigenesis. Cell. 110:751-62.
15. Xia X, Wang P, Sun X, Soriano S, Shum WK, Yamaguchi H, Trumbauer ME, Takashima A, Koo EH, Zheng H. (2002). The aspartate-257 of presenilin 1 is indispensable for mouse development and production of β-amyloid peptides through β-catenin-independent mechanisms. Proc Natl Acad Sci U S A. 99:8760-5.
16. Xia, X., Qian, S., Soriano, S., Wu, Y., Fletcher, A.M., Wang, X.-J., Koo, E.H., Wu, X. and Zheng, H. (2001). Loss of presenilin 1 is associated with enhanced β-catenin signalling and skin tumorigenesis. Proc. Natl. Acad. Sci. USA. 98: 10863-8.
17. S. Soriano, Lu D. Perez RG and Koo, EH. (2001). The amyloidogenic pathway of APP is independent of its cleavage by caspases. J. Biol. Chem. 276: 29045-50.
18. S. Soriano, Kang, D.E., Fu, M., Chevallier, Zheng, H., Pestell, R. and Koo, E.H. (2001). Presenilin 1 Negatively Regulates ß-Catenin/T Cell Factor/Lymphoid Enhancer Factor-1 Signalling Independently of ß-Amyloid Precursor Protein and Notch Processing. J. Cell Biol. 152:785-794.
19. Saura, C.A., Tomita, T., S. Soriano, Takahashi, M.T., Leem, J.-Y., Honda, T., Koo, E.H., Iwatsubo, T. and Thinakaran, G. (2000). The nonconserved hydrophilic loop domain of presenilin 1 is not required for PS endoproteolysis or enhanced Aβ42 production mediated by familial early onset Alzheimer's Disease-linked PS variants. J. Biol. Chem. 275: 17136-17142
20. S. Soriano, Chyung AS, Chen X, Stokin GB, Lee VM, Koo EH. (1999). Expression of b-amyloid precursor protein-CD3γ chimeras to demonstrate the selective generation of Aβ1-40 and Aβ1-42 peptides within secretory and endocytic compartments. J. Biol. Chem. 274: 32295-300
21. Perez RG, S. Soriano, Hayes JD, Ostaszewski B, Xia W, Selkoe DJ, Chen X, Stokin GB, Koo EH. (1999). Mutagenesis identifies new signals for β-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Aβ42. J. Biol. Chem. 274: 18851-6
22. Kang D, S. Soriano, Frosch M, Collins T, Naruse S, Sisodia S, Leibowitz G, Levine F, Koo E (1999). Presenilin 1 facilitates constitutive turnover of β-catenin: differential activity of Alzheimer's disease-linked PS1 mutants in the β-catenin-signalling pathway. J. Neurosci. 19:4229-37