Neurodegenerative Disease Laboratory

Division of Human Anatomy
Department of Pathology and Human Anatomy
School of Medicine
Loma Linda University
Loma Linda, CA 92350

Phone: 909-558-1000 x87010
Fax: 909-558-7950

Profile Photo

Research Interest

There are two main areas of research in my laboratory. The first one concerns the study of early pathogenic mechanisms in Niemann-Pick disease type C and Alzheimer’s disease. These two conditions share pathology hallmarks that stem from early cholesterol dysregulation and inflammation in the brain. Our findings point to altered subcellular distribution and elevated levels of oxysterols as being causative of neuroinflammation and neuronal death, both in Niemann-Pick disease type C and Alzheimer’s disease. These findings have led to recent NIH funding to explore whether targeted inhibition of harmful oxysterol production may have therapeutic value.

We are also interested in improving current methods to diagnose and correct pathological tremors. Characterization and diagnosis of movement disorders require evaluating muscle movement amplitude and frequency in combination with more subjective, non-quantitative scales. These diagnostic approaches often result in misdiagnoses, and it would be desirable to create fully reproducible, objective and quantitative assessment tools. In our lab, we are developing one such tool. Specifically, we are testing a wearable device that wirelessly records movement data from accelerometer, gyroscope and electromyography sensors for its ability to record and classify tremor pathologies. A pilot study with a few volunteers shows distinctly different output patterns between patients with essential tremor and healthy controls from all three sensors. We intend to build on these encouraging results in a study with large cohorts of Parkinson’s disease and essential tremor patients.

Selected Publications

  1. Mayagoitia K, Shin SD, Rubini M, Siebold L, Wilson CG, Bellinger DL, Figueroa JD, Soriano S. Short-term exposure to dietary cholesterol is associated with downregulation of interleukin-15, reduced thigmotaxis and memory impairment in mice. Behav Brain Res. 2020 Sep 1;393:112779. doi: 10.1016/j.bbr.2020.112779. Epub 2020 Jun 22. PubMed PMID: 32585301
  2. Shin SD, Shin A, Mayagoitia K, Siebold L, Rubini M, Wilson CG, Bellinger DL, Soriano S. Loss of amyloid precursor protein exacerbates early inflammation in Niemann-Pick disease type C. J Neuroinflammation. 2019 Dec 17;16(1):269. doi: 10.1186/s12974-019-1663-5. PubMed PMID: 31847862; PubMed Central PMCID: PMC6918596
  3. Shin SD, Shin A, Mayagoitia K, Wilson CG, Bellinger DL, Soriano S. Interferon downstream signaling is activated early in pre-symptomatic Niemann-Pick disease type C. Neurosci Lett. 2019 Jul 27;706:43-50. doi: 10.1016/j.neulet.2019.05.005. Epub 2019 May 5. PubMed PMID: 31067492
  4. Gongol B, Marin TL, Jeppson JD, Mayagoitia K, Shin S, Sanchez N, Kirsch WM, Vinters HV, Wilson CG, Ghribi O, Soriano S. Cellular hormetic response to 27-hydroxycholesterol promotes neuroprotection through AICD induction of MAST4 abundance and kinase activity. Sci Rep. 2017 Oct 24;7(1):13898. doi: 10.1038/s41598-017-13933-9. PubMed PMID: 29066835; PubMed Central PMCID: PMC5654999
  5. Castello MA, Jeppson JD, Soriano S. Moving beyond anti-amyloid therapy for the prevention and treatment of Alzheimer's disease. BMC Neurol.2014 Sep 2;14:169. doi: 10.1186/s12883-014-0169-0. PubMed PMID: 25179671; PubMed Central PMCID: PMC4236650
  6. Castello MA, Soriano S. On the origin of Alzheimer's disease. Trials and tribulations of the amyloid hypothesis. Ageing Res Rev. 2014 Jan;13:10-2. doi: 10.1016/j.arr.2013.10.001. Epub 2013 Nov 16. Review. PubMed PMID: 24252390
  7. Castello MA, Soriano S. Rational heterodoxy: cholesterol reformation of the amyloid doctrine. Ageing Res Rev. 2013 Jan;12(1):282-8. doi: 10.1016/j.arr.2012.06.007. Epub 2012 Jul 6. Review. PubMed PMID: 22771381
  8. Engmann O, Hortobágyi T, Thompson AJ, Guadagno J, Troakes C, Soriano S, Al-Sarraj S, Kim Y, Giese KP. Cyclin-dependent kinase 5 activator p25 is generated during memory formation and is reduced at an early stage in Alzheimer's disease. Biol Psychiatry. 2011 Jul 15;70(2):159-68. doi: 10.1016/j.biopsych.2011.04.011. Epub 2011 May 26. PubMed PMID: 21616478
  9. Nunes A, Pressey SN, Cooper JD, Soriano S. Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis. Neurobiol Dis. 2011 Jun;42(3):349-59. doi: 10.1016/j.nbd.2011.01.028. Epub 2011 Feb 17. PubMed PMID: 21303697
  10. Currais A, Kato K, Canuet L, Ishii R, Tanaka T, Takeda M, Soriano S. Caffeine modulates tau phosphorylation and affects Akt signaling in postmitotic neurons. J Mol Neurosci. 2011 Mar;43(3):326-32. doi: 10.1007/s12031-010-9444-8. Epub 2010 Sep 14. PubMed PMID: 20838929
  11. 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.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. 2010;30(4):302-8. doi: 10.1159/000320482. Epub 2010 Sep 25. PubMed PMID: 20881395
  12. 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. Interaction between oligomers of stefin B and amyloid-beta in vitro and in cells. J Biol Chem. 2010 Jan 29;285(5):3201-10. doi: 10.1074/jbc.M109.024620. Epub 2009 Dec 2. PubMed PMID: 19955183; PubMed Central PMCID: PMC2823404
  13. Currais A, Hortobágyi T, Soriano S. The neuronal cell cycle as a mechanism of pathogenesis in Alzheimer's disease. Aging (Albany NY). 2009 Apr 28;1(4):363-71. doi: 10.18632/aging.100045. Review. PubMed PMID: 20157524; PubMed Central PMCID: PMC2806021
  14. Malik B, Currais A, Soriano S. 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. 2008 Jul;106(2):912-6. doi: 10.1111/j.1471-4159.2008.05446.x. Epub 2008 May 2. PubMed PMID: 18466334
  15. Malik B, Currais A, Andres A, Towlson C, Pitsi D, Nunes A, Niblock M, Cooper J, Hortobágyi T, Soriano S. Loss of neuronal cell cycle control as a mechanism of neurodegeneration in the presenilin-1 Alzheimer's disease brain. Cell Cycle. 2008 Mar 1;7(5):637-46. doi: 10.4161/cc.7.5.5427. Epub 2007 Dec 6. PubMed PMID: 18239458
  16. Lu DC, Soriano S, Bredesen DE, Koo EH. Caspase cleavage of the amyloid precursor protein modulates amyloid beta-protein toxicity. J Neurochem. 2003 Nov;87(3):733-41. doi: 10.1046/j.1471-4159.2003.02059.x. PubMed PMID: 14535955
  17. Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, Zheng H, Koo EH. Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis. Cell. 2002 Sep 20;110(6):751-62. doi: 10.1016/s0092-8674(02)00970-4. PubMed PMID: 12297048
  18. Xia X, Qian S, Soriano S, Wu Y, Fletcher AM, Wang XJ, Koo EH, Wu X, Zheng H. Loss of presenilin 1 is associated with enhanced beta-catenin signaling and skin tumorigenesis. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10863-8. doi: 10.1073/pnas.191284198. Epub 2001 Aug 21. PubMed PMID: 11517342; PubMed Central PMCID: PMC58565
  19. Soriano S, Lu DC, Chandra S, Pietrzik CU, Koo EH. The amyloidogenic pathway of amyloid precursor protein (APP) is independent of its cleavage by caspases. J Biol Chem. 2001 Aug 3;276(31):29045-50. doi: 10.1074/jbc.M102456200. Epub 2001 Jun 7. PubMed PMID: 11397796
  20. Soriano S, Kang DE, Fu M, Pestell R, Chevallier N, Zheng H, Koo EH. Presenilin 1 negatively regulates beta-catenin/T cell factor/lymphoid enhancer factor-1 signaling independently of beta-amyloid precursor protein and notch processing. J Cell Biol. 2001 Feb 19;152(4):785-94. doi: 10.1083/jcb.152.4.785. PubMed PMID: 11266469; PubMed Central PMCID: PMC2195782
  21. Soriano S, Chyung AS, Chen X, Stokin GB, Lee VM, Koo EH. Expression of beta-amyloid precursor protein-CD3gamma chimeras to demonstrate the selective generation of amyloid beta(1-40) and amyloid beta(1-42) peptides within secretory and endocytic compartments. J Biol Chem. 1999 Nov 5;274(45):32295-300. doi: 10.1074/jbc.274.45.32295. PubMed PMID: 10542269
  22. Perez RG, Soriano S, Hayes JD, Ostaszewski B, Xia W, Selkoe DJ, Chen X, Stokin GB, Koo EH. Mutagenesis identifies new signals for beta-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Abeta42. J Biol Chem. 1999 Jul 2;274(27):18851-6. doi: 10.1074/jbc.274.27.18851. PubMed PMID: 10383380