Stem Cells, Parkinson Disease, Alzheimer Disease, Neurogenesis, Differentiation, Learning and Memory, Neurodegeneration, Neurotrophins
2006-2007 Postdoctoral Fellowship in Stem Cell Biology (California Institute for Regenerative Medicine)
2002-2004 NIA Neurobiology of Aging Training Grant (PI: C Cotman, annually awarded)
1997-2001 NIA Neuroplasticity of Aging Training Grant (PI: F Gage, annually awarded)
2001 Merck fellowship/Neurosciences Graduate Training Program
2000 Teaching Excellence Award, UC San Diego Cognitive Science Department
1997 Markey Fellowship, University of California, San Diego
2005-2007 Postgraduate Researcher
Department of Neurobiology and Behavior
University of California, Irvine
Irvine, CA 92697-4545
Mentor: Frank LaFerla, Ph.D.
2002-2005 Postgraduate Researcher
Department of Neurobiology and Behavior
University of California, Irvine
Irvine, CA 92697-4545
Mentor: Carl Cotman, Ph.D.
July 2002 Ph.D. in Neurosciences
University of California, San Diego
Thesis Advisor: Mark Tuszynski, M.D.,Ph.D.
The primary focus of my lab is to examine the underlying molecular mechanisms that drive the development of Alzheimer’s disease (AD) and Parkinson’s disease (PD), the two most common forms of age-related neurodegeneration. My lab uses stem cells, including patient-derived induced pluripotent stem cells (iPSCs), to study the role of neural and immune cell populations in these disorders. We also generate and use transgenic mouse models of AD and PD to test potential therapies and examine the relationships between peripheral and central immunity and their influence on disease progression. Among our current studies, we are using iPSCs to generate human microglia and understand the effects of disease-associated genetic risk factors on microglial function and AD pathology. Working with immune-deficient AD mouse models, we have also recently uncovered an important role for the adaptive immune system in AD, finding that peripheral immune populations slow the development of beta-amyloid pathology by modulating microglial function. In collaboration with colleagues in the UCI Institute for Immunology, Dr. Blurton-Jones is now further examining the role of peripheral immune senescence in AD and determining precisely which adaptive immune cell populations are responsible for the observed effects on disease progression.
1. Melega WP, Raleigh MJ, Stout DB, DeSallas AA, Cherry SR, Blurton-Jones M, Morton GG, Huang SC, and Phelps ME (1996) Longitudinal Behavioral and 6-[18F]Fluoro-L-DOPA-PET Assessment of MPTP-Hemiparkinsonian Monkeys. Experimental Neurology. 141: 318-329.
2. Blurton-Jones M, Roberts J, and Tuszynski MH (1999) Estrogen Receptor Immunoreactivity in the Adult Primate Brain: Neuronal Distribution and Association with p75, trk A, and Choline Acetyltransferase. Journal of Comparative Neurology. 405:529-542.
3. Blurton-Jones M and Tuszynski MH (2001) Reactive astrocytes express estrogen receptors in the injured primate brain. Journal of Comp. Neurology. 433:115-123.
4. Taber KH, Murphy DD, Blurton-Jones M, and Hurley RA (2001) An Update on Estrogen: Higher Cognitive Function, Receptor Mapping, Neurotrophic Effects. Journal of Neuropsychiatry and Clinical Neuroscience.13:313-317.
5. Blurton-Jones M and Tuszynski MH (2002) Estrogen receptor-ß co-localizes extensively with parvalbumin-labeled inhibitory neurons in the cortex, amygdala, basal forebrain, and hippocampal formation of intact and ovariectomized adult rats. Journal of Comparative Neurology. 452: 276-287.
6. Blurton-Jones M, Kuan PN, and Tuszynski MH (2004) Anatomical evidence for transsynaptic influences of estrogen on brain derived neurotrophic factor expression. Journal of Comparative Neurology. 468: 347-360.
7. Rissman RA*, Poon WW*, Blurton-Jones M*, Oddo S, Torp R, Vitek MP, LaFerla FM, Rohn TT, Cotman CW (2004) Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology. Journal of Clinical Investigation. 114: 121-130. * RR, WP, & MBJ contributed equally to this work.
8. Cribbs DH, Poon WW, Rissman RA, Blurton-Jones M. (2004) Caspase-mediated degeneration in Alzheimer’s disease. American Journal of Pathology. 165:353-355.
9. Cotman CW, Poon WW, Rissman RA, Blurton-Jones M. (2005) The role of caspase cleavage of tau in alzheimer's disease neuropathology. Journal of Neuropathology and Experimental Neurology. 64:104-112.
10. Taylor AM*, Blurton-Jones M*, Rhee SW, Cribbs DH, Cotman CW, Jeon NL (2005) A Microfluidic Neuronal Culture Platform for CNS Axonal Injury, Regeneration and Transport. Nature Methods. 2:599-605 *AMT & MBJ contributed equally to this work.
11. Blurton-Jones M and Tuszynski MH (2006) Estradiol-induced modulation of estrogen receptor-? and GABA within the adult neocortex: a potential trans-synaptic mechanism for estrogen modulation of BDNF. J. Comp. Neurology. 499: 603-612.
12. Blurton-Jones M, LaFerla, FM. (2006) Pathways by which Aß facilitates tau pathology. Current Alzheimer Research. 3:437-448.
13. Parachikova A, Agadjanyan MG, Cribbs DH, Blurton-Jones M, Perreau V, Rogers J, Beach TG, Cotman CW (2007) Inflammatory changes parallel the early stages of Alzheimer’s disease. Neurobiology of Aging. 28(12): 1821-33.
14. Shapiro LA, Ng K, Kinyamu R, Whitaker-Azmitia P, Geisert EE, Blurton-Jones M, Korn MJ, Zhou QY, Ribak C. (2007) Origin, migration and fate of newly generated neurons in the adult rodent piriform cortex. Brain Structure and Function. 212(2):133-148.
15. Yamasaki TR, Blurton-Jones M, Morrissette DA, Kitazawa M, Oddo S and LaFerla FM (2007) Neural Stem Cells Improve Memory in an Inducible Mouse Model of Neuronal Loss. Journal of Neuroscience. 27(44):11925-33.
16. Tseng BP, Green KN, Chan JL, Blurton-Jones M, LaFerla FM (2008) Aß inhibits the proteasome and enhances amyloid and tau accumulation. Neurobiology of Aging. 29(11):1607-1618. PMCID2664168
17. Poon WW, Blurton-Jones M, Tu CH, Feinberg LM, Chabrier MA, Harris JW, Jeon NL, Cotman CW (2009) ß-amyloid impairs axonal BDNF retrograde trafficking. Neurobiology of Aging: Jun 18. PMCID3038182.
18. McAlpine FE, Lee JK, Harms AS, Ruhn KA, Blurton-Jones M, Hong J, Das P, Golde TE, LaFerla FM, Oddo S, Blesch A, Tansey MG. (2009). Inhibition of soluble TNF signaling in a mouse model of Alzheimer’s disease prevents pre-plaque amyloid-associated neuropathology. Neurobiology of Disease 34: 163-177. PMID: 19320056
19. Lopes JP, Blurton-Jones M, Yamazaki TR, Agostinho P and LaFerla F.M. (2009) Activation of cell cycle proteins in transgenic mice in response to neuronal loss but not Aß and tau pathology. J Alzheimer’s Disease 16: 541-9. PMID: 19276549.
20. Clinton LK*, Blurton-Jones M*, Myczek K*, Trojanowski JQ, LaFerla FM. (2010). Synergistic Interactions Among Aß, Tau, and ?-Synuclein: Acceleration of Neuropathology and Cognitive Decline. Journal of Neuroscience. 30(21):7281-7289. *MBJ, CLK, & MK contributed equally to this work. PMC Journal - In Process.
21. Koike MA, Green KN, Blurton-Jones M¬, LaFerla FM. (2010) Oligemic Hypoperfusion Differentially Affects Tau and Amyloid-?. American Journal of Pathology. 177(1):300-10.
22. Blurton-Jones M, Kitazawa M, Martinez-Coria H, Castello N, Muller FJ, Loring JF, Yamasaki T, Poon WW, Green KN, LaFerla FM. (2009) Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease. Proceedings of the National Academy of Sciences USA. 106:13594-13599. PMCID2715325.
23. Freude KK, Penjwini M, Davis JL, Laferla FM, Blurton-Jones M. (2011) Soluble amyloid precursor protein induces rapid neural differentiation of human embryonic stem cells. Journal of Biological Chemistry. 286(27):24264-74. PMID:21606494.
24. Walls KC, Coskun P, Gallegos-Perez JL, Zadourian N, Freude K, Rasool S, Blurton-Jones M, Green KN, and LaFerla FM. (2012) Swedish Alzheimer's mutation induces mitochondrial dysfunction mediated by HSP60 mislocalization of APP and beta-amyloid. Journal of Biological Chemistry. 287(36):30317-27. PMC3436283.
25. Marsh SE, Blurton-Jones M. (2012) Examining the mechanisms that link ß-amyloid and a-synuclein pathologies. Alzheimer’s Research & Therapy. 4(2):11-19. PMID:22546279.
26. Chabrier M*, Blurton-Jones M*, Agazaryan A, Nerhus J, Martinez-Coria H, LaFerla FM. (2012) Soluble A? promotes wild-type tau pathology in vivo. Journal of
Neuroscience. 32 (48): 17345-50. PMID: 23197725 *MBJ and MC contributed equally to this work.
27. Chen W, Blurton-Jones M. (2012) Can stem cells be used to treat or model Alzheimer Disease? Stem Cells. 30(12):2612-8. PMID:22997040.
28. Rodriguez-Ortiz CJ, Hoshino H, Cheng D, Liu-Yescevitz L, Blurton-Jones M, Wolozin B, Laferla FM, Kitazawa M. (2013) Neuronal-Specific Overexpression of a Mutant Valosin-Containing Protein Associated with IBMPFD Promotes Aberrant Ubiquitin and TDP-43 Accumulation and Cognitive Dysfunction in Transgenic Mice. American Journal of Pathology. 183(2):504-15. PMID: 23747512.
29. Blurton-Jones M, Castello NA, Agazaryan AA, Müller FJ, Loring JF, Spencer B, Masliah E, LaFerla FM. (2014) Neural Stem Cells Genetically-modified to express Neprilysin reduce pathology in Alzheimer Transgenic Models. Stem Cell Research and Therapy. 5(2), 46-59. PMID: 25022790.
30. Ager R, Davis JL, Agazaryan A, Benavente F, Poon WW, LaFerla FM, Blurton-Jones M (2014) Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of Alzheimer's disease and neuronal loss. Hippocampus. Dec 19th. PMID: 25530343.
31. Goldberg NRS, Caesar J, Park A, Sedgh S, Finogenov G, Masliah E, Davis J, Blurton-Jones M (2015) Neural stem cell transplantation rescues cognitive and motor dysfunction in a transgenic model of Dementia with Lewy Bodies by elevating BDNF and improving glutamatergic and dopaminergic function. Stem Cell Reports. In Press.
1. Blurton-Jones M, Yamasaki TR, LaFerla FM. (2009). Improving Memory with Stem Cell Transplantation. Regulatory Networks in Stem Cells, Eds. VK Rajesekhar & MC Vemuri. Humana Press.
2. Blurton-Jones M, Nerhus, J, LaFerla FM. (2012). Transplanting stem cells into the brain. Human Stem Cell Manual 2nd edition, Eds. J Loring & S Peterson. Elsevier.
3. Goldberb, N., Blurton-Jones, M. (2014). Can Stem Cells be used to Enhance Cognition?. In S. Knafo (Ed.), Cognitive Enhancement. Elsevier.
4. Marsh, S., Blurton-Jones, M. Prospects of Neural Stem Cell Therapy for Alzheimer’s Disease. In A. Shetty (Ed.), Neural Stem Cells in Health and Disease. World Scientific Publishing Company. Accepted: 2014.
5. Abud, E., Blurton-Jones, M. Could Stem Cells be used to treat or model Alzheimer’s Disease? In M. Tuszynski (Ed.), Translational Neuroscience. Springer Science and Business Media. Accepted: 2015.
RF1 AG048099-01 (PI:Blurton-Jones)
The role of TREM2 in human microglial function and Alzheimer disease pathogenesis. 09/15/14 – 08/31/19
California Institute for Regenerative Medicine (CIRM)
Optimizing The Differentiation And Expansion Of Microglial Progenitors From Human Pluripotent Stem Cells For The Study And Treatment Of Neurological Disease.
08/01/15 – 07/31/18
P50 AG016573 (Core Leader: Blurton-Jones)
University of California, Irvine Alzheimer Disease Research Center iPSC Core.
05/01/15 - 04/31/20
Examining the role of TREM2 in AD pathogenesis with iPSC-derived microglia
10/1/14 - 9/31/17
2006-present International Society for Stem Cell Research
1998-present Society for Neuroscience
Interdepartmental Neuroscience Program