Masashi Kitazawa

Picture of Masashi Kitazawa
Associate Professor, Center for Occupational and Environmental Health (COEH)
School of Medicine
Associate Professor, Environmental and Occupational Health
Public Health
Member, Institute for Memory Impairments and Neurological Disorders (UCI MIND)
Ph.D., Iowa State University, 2003, Toxicology
M.S., University of California, Irvine, 2000, Environmental Toxicology
B.S., California State University, San Bernardino, 1997, Chemistry
Phone: (949) 824-1255
Fax: (949) 824-2345
Email: kitazawa@uci.edu
University of California, Irvine
100 Theory Dr., Suite 100
Irvine, CA 92617
Research Interests
Alzheimer's disease, environmental risk factors, air pollution, inflammation, microglia
Research Abstract
My primary research emphasis centers on understanding the molecular pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD) and the impact of neuroinflammation elicited endogenously by disruption of normal immune responses by aging or by exogenous environmental factors, such as chronic exposure to environmental chemicals and toxicants. By using multiple experimental platforms including transgenic mouse models of the disease, primary cultures and established cell culture models, and organotypic slices, my laboratory is investigating key cellular signaling cascades in microglia and astrocytes that are dysregulated in early phase of AD.
Awards and Honors
2019 Excellence in Graduate Teaching Award, School of Medicine, UCI
2015 Senate Award for Distinguished Early Career Research, UC Merced
2007 Al Nichols Award, Institute for Brain Aging and Dementia, UCI
2003 Research Excellence Award, Iowa State University
Publications
2021

Hsu, H.W., Rodriguez-Ortiz, C.J., Zumkehr, J., and Kitazawa, M. Inflammatory cytokine, IL-1ß downregulates endothelial LRP1 via microRNA-mediated gene silencing. Neuroscience 453:69-80.

Subramanian, V.S., Teafatiller, T., Agrawal, A., Kitazawa, M. and Marchant, J.S. Effect of lipopolysaccharide and TNFa on neuronal ascorbic acid uptake. Mediators of Inflammation 2021:4157132.

2020

Rodriguez-Ortiz, C.J., Prieto, G.A., Martini, A.C., Forner, S., Trujillo-Estrada, L., LaFerla, F.M., Baglietto-Vargas, D., Cotman, C.W., and Kitazawa, M. miR-181a negatively modulates synaptic plasticity in hippocampal cultures and its inhibition rescues memory deficits in a mouse model of Alzheimer’s disease. Aging Cell 19(3):e13118.

Lim, S.L., Tran, D.N., Kieu, Z., Chen, C., Villanueva, E., Ghiaar, S., Gallup, V., Zumkehr, J., Cribbs, D.H., Rodriguez-Ortiz, C.J., and Kitazawa, M. Genetic ablation of hematopoietic cell kinase accelerates Alzheimer’s disease-like neuropathology in Tg2576 mice. Mol. Neurobiol. 57(5):2447-2460.

Lim, S.L., Hsu, H.W. Rodriguez-Ortiz, C.J., Wu, J., Zumkehr, J., Kilian, J., Vidal, J., Ayata, P., and Kitazawa, M. Chronic copper exposure directs microglia towards degenerative expression signatures in wild-type and J20 mouse model of Alzheimer’s disease. J. Trace Elem. in Med. Biol.62:126578.

2019

Forner, S., Martini, A.C., Prieto, G.A., Dang., C.T., Rodriguez-Ortiz, C.J., Reyes-Ruiz, J.M., Trujillo-Estrada, L., Cunha, C., Andrews, E.J., Phan, J., Ha., J.V., Chang, A.V.Z.D., Levites, Y., Cruz, P.E., Ager, R., Medeiros, R., Kitazawa, M., Glabe, C.G., Cotman, C.W., Golde, T., Baglietto-Vargas, D., and LaFerla, F.M. Intra- and extracellular amyloid-beta overexpression via adeno-associated virus-mediated gene transfer impairs memory and synaptic plasticity in the hippocampus. Sci. Rep. 9(1):15936.

Martini, A.C., Gomez-Arboledas, A., Forner, S., Rodriguez-Ortiz, C.J., McQuade, A., Danhash, E., Phan, J., Javonillo, D., Ha, J.V., Tram, M., Trujillo-Estrada, L., Cunha, C., Ager, R., Davila, J.C., Kitazawa, M., Blurton-Jones, M., Gutierrez, A., Baglietto-Vargas, D., Medeiros, R., and LaFerla F.M. Amyloid-beta impairs TOM1-mediated IL-1R1 signaling Proc. Nat. Acad. Sci. 116(42):21198-21206.

Huat, T.J., Camats-Perna, J., Newcombe, E.A., Valmas, N., Kitazawa, M., and Medeiros, R. Metal toxicity links to Alzheimer’s disease and neuroinflammation. J. Mol. Biol. 431(9):1843-1868.

Hsu, H.W., Rodriguez-Ortiz, C.J., Lim, S.L., Zumkehr, J., Kilian, J.G., Vidal, J., and Kitazawa, M. Copper-induced upregulation of microRNAs directs the suppression of endothelial LRP1 in Alzheimer’s disease model. Toxicol. Sci. 170(1):144-156.

2018

Bagliett-Vargas, D., Prieto, A.G., Limon, A., Forner, S., Rodriguez-Ortiz, C.J., Ikemura, K., da Cunha, C., Agar, R.A., Medeiros, R., Trujillo-Estrada, L., Martini, A.C., Kitazawa, M., Davila, J.C., Cotman, C.W., Gutierrez, A., and LaFerla F.M. Impaired AMPA signaling and cytoskeletal alterations induce early synaptic dysfunction in a mouse model of Alzheimer’s disease. Aging Cell Jun 6:e12791.

Zumkehr, J., Rodriguez-Ortiz, C.J., Medeiros, R., and Kitazawa, M. Inflammatory cytokine, IL-1ß, regulates glial glutamate transporter via microRNA-181a in vitro. J. Alz. Dis. 63(3):965-975.

Hsu, H.W., Bondy, S.C., and Kitazawa, M. Environmental and dietary exposure to copper and its cellular mechanisms linking to Alzheimer’s disease. Toxicol. Sci. 163(2):338-345.

Kilian, J.G. and Kitazawa, M. The emerging risk of exposure to air pollution on cognitive decline and Alzheimer’s disease – Evidence from epidemiological and animal studies. Biomedical J. 41(3):141-162.

Lim, S.L., Tran, D.N., Zumkehr, J., Chen, C., Ghiaar, S., Kieu, Z., Villanueva, E., Gallup, V., Rodriguez-Ortiz, C.J., and Kitazawa, M. Inhibition of hematopoietic cell kinase dysregulates microglial function and accelerates early stage Alzheimer’s disease-like neuropathology. Glia 66(12):2700-2718.

2017

Nakazono, T, Lam, T.N., Patel, A.Y., Kitazawa, M., Saito, T., Saido, T.C., and Igarashi, K.M. Impaired in vivo gamma oscillations in the medial entorhinal cortex of knock-in Alzheimer model. Front. Systems Neurosci. 11:48. PMID: 28713250

Kilian, J.G., Hsu, H.W., Mata, K., Wolf, F.W., and Kitazawa, M. Astrocyte transport of glutamate and neuronal activity reciprocally modulate tau pathology in Drosophila. Neuroscience 348:191-200. PMID: 28215745


2016

Kitazawa, M., Hsu, H.W., and Medeiros, R. Copper exposure perturbs brain inflammatory responses and impairs clearance of amyloid-beta. Toxicol. Sci. 152(1):194-204.

Rodriguez-Ortiz, C.J., Flores, J.C., Valenzuela, J., Rodriguez, G.J., Zumkehr, J., Kimonis, V.E., and Kitazawa, M. (2016) The myoblast C2C12 transfected with mutant valosin-containing protein (VCP) exhibits resolution deficiencies upon oxidative stress. Am. J. Pathol. 186(6):1623-1634.


2015

Zumkehr, J., Rodriguez-Ortiz, C.J., Cheng, D., Kieu, Z., Wai, T., Hawkins, C., Kilian, J., Lim, S.L., Medeiros, R., and Kitazawa, M. (2015) Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer’s disease. Neurobiol. Aging. 36(7):2260-2271. PMID: 25964214

Lim, S.L., Rodriguez-Ortiz, C.J., and Kitazawa, M. (2015) Infection, systemic inflammation and Alzheimer’s disease. Microbes and Infection 17(8):549-556. PMID: 25912134

Dunn, H.C., Ager, R.R., Baglietto-Vargas, D., Cheng, D., Kitazawa, M., Cribbs, D.H., and Medeiros, R. (2015) Restoration of lipoxin A4 signaling reduces Alzheimer’s disease-like pathology in the 3xTg-AD mouse model. J. Alz. Dis. 43(3):893-903. PMID: 25125468 PMCID: PMC4319708


2014

Rodriguez-Ortiz, C.J., Baglietto-Vargas, D., Martinez-Coria, H., LaFerla, F.M. and Kitazawa, M. (2014) Up-regulation of miR-181 decreases c-Fos and SIRT-1 in the hippocampus of 3xTg-AD mice. J. Alz. Dis. 42(4):1229-1238. PMID: 25024332

Elmore M.R., Najafi, A.R., Koike, M.A., Dagher, N.N., Spangenberg, E.E., Rice, R.A., Kitazawa, M., Matusow, B., Nguyen, H., West, B.L. and Green, K.N. (2014) Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in adult brain. Neuron 82(2):380-397. PMID: 24742461

Medeiros, R., Castello, N.A., Cheng, D., Kitazawa, M., Baglietto-Vargas, D., Green, K.N. and LaFerla, F.M. (2014) a7 nicotinic receptor agonist enhances cognition in aged 3xTG-AD mice with robust plaques and tangles. Am. J. Pathol. 184:520-529. PMID: 24269557

Baglietto-Vargas, D., Kitazawa, M., Le, E.J., Estrada-Hernandez, T., Rodriguez-Ortiz, C.J., Medeiros, R., Green, K.N. and LaFerla, F.M. (2014) Endogenous murine tau promotes neurofibrillary tangles in 3xTg-AD mice without affecting cognition. Neurobiol. Dis. 62:407-415. PMID: 24176788


2013

Rodriguez-Ortiz, C.J., Hoshino, H., Cheng, D., Liu-Yescevitz, L., Blurton-Jones, M., Wolozin, B., LaFerla, F.M. and 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. Am. J. Pathol. 183(2):504-515. PMID: 23747512, PMCID: PMC3730785

Medeiros, R., Kitazawa, M., Passos, G. F., Baglietto-Vargas, D., Cheng, D., Cribbs, D. H., and LaFerla, F. M. (2013) Aspirin-triggered lipoxin A4 stimulates alternative activation of microglia and reduces Alzheimer disease-like pathology in mice. Am. J. Pathol. 182(5):1780-1789. PMID 23506847, PMCID: N/A


2012

Nalbandian A., Llewellyn K. J., Kitazawa, M., Hon, Y., Badadani, M., Ewards, R., Nguyen, C., Mukherjee, J., Watts, J., Mozaffar, T., Weiss, J., and Kimonis, V. E. (2012) The homozygous VCP(R155H/R155H) mouse model exhibits accelerated VCP disease-associated pathology. PLoS One 7(9):e46308. PMID: 23029473, PMCID: PMC3460820

Medeiros, R., Kitazawa, M., Cheng, D., Chabrier, M., Baglietto-Vargas, D., Moeller, A., Kling, A., Green, K. N., and LaFerla, F. M. (2012) Calpain inhibitor A-705253 mitigates Alzheimer disease-like pathology and cognitive decline in aged 3xTg-AD mice. Am. J. Pathol. 181(2):616-625. PMID: 22688056

Kitazawa, M., Medeiros, R., and LaFerla, F. M. (2012) Transgenic mouse models of Alzheimer disease: Developing a better model as a tool for therapeutic interventions. J. Curr. Pharmaceut. Design 18(8):1131-1147. PMID: 22288400


2001-2011

Morroni, F., Kitazawa, M., Drago, D., Cheng, D., Medeiros, R., and LaFerla, F. M. (2011) Repeated physical training and environmental enrichment induce neurogenesis and synaptogenesis following neuronal injury in an inducible mouse model. J. Brain Behav. Sci. 1(4):199-209. PMID: N/A

Kitazawa, M., Cheng, D., Tsukamoto, M., Koike, M., Wes, P., Vasilevko, V., Cribbs, D. H., and LaFerla, F. M. (2011) Blocking interleukin-1 signaling rescues cognition, attenuates tau pathology and restores neuronal beta-catenin pathway in an Alzheimer's disease model. J. Immunol. 187(12):6539-6549. PMID: 22095718, PMCID: PMC4072218

Medeiros, R., Kitazawa, M., Caccamo, A., Baglietto-Vargas, D., Estrada, T., Fisher A., and LaFerla, F. M. (2011) Loss of muscarinic M1 receptor exacerbates Alzheimer disease-like pathology in 3xTgAD and Tg-SwDI mice. Am. J. Pathol. 179(2):980-991. PMID: 21704011, PMCID: PMC3157199

Koike, M. A., Garcia, F. G., Kitazawa, M., Green, K. N., and LaFerla F. M. (2011) Long term changes in phospho-APP and tau aggregation in the 3xTg-AD mice following cerebral ischemia. Neurosci. Lett. 495(1):55-59. PMID: 21419194, PMCID: PMC3099741

Sy, M., Kitazawa, M., Medeiros, R., Whitman, L., Cheng, D., Lane, T. E., and LaFerla, F. M. (2011) Inflammation induced by infection potentiates tau pathology in transgenic mice. Am. J. Pathol. 178(6):2811-2822. PMID: 21531375, PMCID: PMC3124234

Badadani, M., Watts, G. D., Vesa, J., Nalbandian, A., Kitazawa, M., Su, H., Tanaja, J., Dec, E., Wallace, D. C., Mukherjee, J., Caiozzo, V., Warman, M., and Kimonis, V. E. (2010) VCP associated inclusion body myopathy and Paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease. PLoS One 5(10):e13183. PMID: 20957154, PMCID: PMC2950155

Hasegawa, T., Mikoda, N., Kitazawa, M., and LaFerla, F.M. (2010) Treatment of Alzheimer's disease with anti-homocysteic acid antibody in 3xTg-AD male mice. PLoS One 5(1):e8593. PMID: 20098691, PMCID: PMC2808336

Martinez-Coria, H., Green, K. N., Billings, L. M., Kitazawa, M., Albrecht, M., Rammes, G., Parsons, C. G., Gupta, S., Bannerjee, P., and LaFerla, F. M. (2010) Memantine improves cognition and reduces Alzheimer’s-like neuropathology in transgenic mice. Am. J. Pathol. 176(2):870-880. PMID: 20042680, PMCID: PMC2808092

Blurton-Jones, M., Kitazawa, M., Martinez-Coria, H., Muller, F. J., Loring, J. F., Poon, W. W., Green, K., N., and LaFerla, F. M. (2009) Neural stem cells rescue cognition and increase synaptic density in Alzheimer disease mice via a neurotrophic mechanism. Proc. Nat. Acad. Sci. U.S.A. 106(32):13594-13599. PMID: 19633196, PMCID: PMC2715325

Kitazawa, M., Vasilevko, V., Cribbs, D. H., and LaFerla, F. M. (2009) Immunization with amyloid-beta attenuates inclusion body myositis-like myopathology and motor impairment in a transgenic mouse model. J. Neurosci. 29(19):6132-6141. PMID: 19439591, PMCID: PMC3049190

Kitazawa, M., Cheng, D., and LaFerla, F. M. (2009) Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD. J. Neurochem. 108(6):1550-1560. PMID: 19183260

Shtifman, A., Ward, C. W., Laver, D. R., Banister, M. L., Lopez, J. R., Kitazawa, M., LaFerla, F. M., Ikemoto, N., and Querfurth, H. W. (2008) Amyloid-beta protein impairs Ca2+ release and contractility in skeletal muscle from inclusion body myositis mice. Neurobiol. Aging 31(12):2080-2090. PMID: 19108934, PMCID: PMC2901770

Kanthasamy, A. G., Kitazawa, M., Yang, Y., Anantharam, V., and Kanthasamy, A. (2008) Environmental neurotoxin dieldrin induces apoptosis via caspase-3-dependent proteolytic activation of protein kinase C delta (PKCdelta): Implications for neurodegeneration in Parkinson's disease. Mol. Brain 1(1):12. PMID: 18945348

Kitazawa, M., Trinh, D. N., and LaFerla, F. M. (2008) Inflammation induces tau pathology in inclusion body myositis model via GSK-3ß. Ann. Neurol. 64(1):15-24. PMID: 18318434

Yamasaki, T. R., Blurton-Jones, M., Morrissette, D. A., Kitazawa, M., Odd, S., and LaFerla, F. M. (2007) Neural stem cells improve memory in an inducible mouse model of neuronal loss. J. Neurosci. 27(43):11925-11933. PMID: 17978032

Oddo, S., Vasilevko, V., Caccamo, A., Kitazawa, M., Cribbs, D. H., and LaFerla, F. M. (2006) Reduction of soluble Abeta and tau, but not soluble Abeta alone, ameliorates cognitive decline in transgenic mice with plaques and tangles. J. Biol. Chem. 281(51):39413-39423. PMID: 17056594

Kitazawa, M., Green, K. N., Caccamo, A., and LaFerla, F. M. (2006) Genetically augmenting Abeta42 levels in skeletal muscle exacerbates inclusion body myositis-like pathology and motor deficits in transgenic mice. Am. J. Pathol. 168(6):1986-1997. PMID: 16723713, PMCID: PMC1606633

Sugarman, M. C., Kitazawa, M., Baker, M., Caiozzo, V. J., Querfurth, H. W., and LaFerla, F. M. (2006) Pathogenic accumulation of APP in fast twitch muscle of IBM patients and a transgenic model. Neurobiol. Aging. 27(3):423-432. PMID: 15950323

LaFerla, F. M. and Kitazawa, M. (2005) Antipodal Effects of p25 on synaptic plasticity, learning and memory - too much of a good thing is bad. Neuron 48:711-712. PMID: 16337907

Kitazawa, M., Oddo, S., Yamasaki, T. R., Green, K. N., and LaFerla, F. M. (2005) LPS-induced inflammation exacerbates tau pathology by a cdk5-mediated pathway in a transgenic model of Alzheimer’s disease. J. Neurosci. 25(39):8843-8853. PMID: 16192374

Latchoumycandane, C., Anantharam, V., Kitazawa, M., Yang, Y., Kanthasamy, A., and Kanthasamy, A. G. (2005) Protein Kinase C Delta is a key downstream mediator of manganese-induced apoptosis in dopaminergic Neuronal Cells. J. Pharmacol. Exp. Ther. 313(1):46-55. PMID: 15608081

Kitazawa, M., Anantharam, V., Yang, Y., Hirata, Y., Kanthasamy, A., and Kanthasamy, A. G. (2005) Activation of protein kinase C-delta by proteolytic cleavage contributes to manganese-induced apoptosis in dopaminergic cells: protective role of Bcl-2. Biochem. Pharmacol. 69(1):133-146. PMID: 15588722

Kanthasamy, A. G., Kitazawa, M., Kanthasamy, A., and Anantharam, V. (2005) Dieldrin-induced neurotoxicity: relevance to Parkinson’s disease pathogenesis. Neurotoxicology 26(4):701-719. PMID: 16112328

Anantharam, V., Kitazawa, M., Latchoumycandane, C., Kanthasamy, A., and Kanthasamy, A. G. (2004) Blockade of PKC-delta proteolytic activation by loss of function mutants rescues mesencephalic dopaminergic neurons from methylcyclopentadienyl manganese (MMT)-induced apoptotic cell death. Annals. N.Y. Acad. Sci. 1035:271-289. PMID: 15681813

Kitazawa, M., Yamasaki, T. R., and LaFerla, F. M. (2004) Microglia as a potential bridge between amyloid-beta and tau. Annals. N.Y. Acad. Sci. 1035:85-103. PMID: 15681802

Tseng, B. P., Kitazawa, M., and LaFerla, F. M. (2004) Amyloid-beta: The inside story. Curr. Alzheimer Res. 1(4):231-239. PMID: 15975052

Kitazawa, M., Anantharam, V., Kanthasamy, A., and Kanthasamy, A. G. (2004) Dieldrin promotes proteolytic cleavage of poly(ADP-ribose) polymerase and apoptosis in dopaminergic cells: protective effect of mitochondrial anti-apoptotic protein Bcl-2. Neurotoxicology 25(4):589-598. PMID: 15183012

Oddo, S., Caccamo, A., Kitazawa, M., Tseng, B., and LaFerla, F. M. (2003) Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer’s disease. Neurobiology of Aging 24:1063-1070. PMID: 14643377

Kanthasamy, A. G., Kitazawa, M., Kaul, S., Yang, Y., Lahiri, D. K., Anantharam, V. and Kanthasamy, A. (2003) Proteolytic activation of proapoptotic kinase PKC-delta is regulated by overexpression of Bcl-2: implication for oxidative stress and environmental factors of Parkinson’s disease. Annals. N.Y. Acad. Sci. 1010:683-686. PMID: 15033812

Kanthasamy, A. G., Kitazawa, M., Kanthasamy, A., Anantharam, V. (2003) Role of proteolytic activation of protein kinase C-delta in oxidative stress-induced apoptosis. Antioxidant and redox signaling 5(5):609-620. PMID: 14580317

Kaul, S., Kanthasamy, A., Kitazawa, M., Anantharam, V., and Kanthasamy, A. G. (2003) Caspase-3-dependent proteolytic activation of protein kinase C-delta mediates and regulates 1-methyl-4-phenylpyridinium (MPP+)-induced apoptotic cell death in dopaminergic cells: relevance to oxidative stress in dopaminergic degeneration. Eur. J. Neurosci. 18(6):1387-1401. PMID: 14511319

Kitazawa, M., Anantharam, V., and Kanthasamy, A. G. (2003) Dieldrin induces apoptosis by promoting caspase-3-dependent proteolytic cleavage of protein kinase C-delta in dopaminergic cells: relevance to oxidative stress and dopaminergic degeneration. Neuroscience 119(4):945-964. PMID: 12831855

Kitazawa, M., Wagner, J. R., Kirby, M. L., Anantharam, V. and Kanthasamy, A. G. (2002) Oxidative stress and mitochondrial-mediated apoptosis in dopaminergic cells exposed to methylcyclopentadienyl manganese tricarbonyl (MMT). J. Pharm. Exp. Ther. 302(1):26-35. PMID: 12065696

Anantharam, V., Kitazawa, M., Wagner, J. R., Kaul, S. and Kanthasamy, A. G. (2002) Caspase-3-dependent proteolytic cleavage of protein kinase C-delta is essential for oxidative stress-mediated dopaminergic cell death following exposure to methylcyclopentadienyl manganese tricarbonyl (MMT). J. Neurosci. 22(5):1738-1751. PMID: 11880503

Kitazawa, M., Anantharam, V., and Kanthasamy, A. G. (2001) Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptotic cell death in dopaminergic cells. Free Rad. Biol. Med. 31(11):1473-1485. PMID: 11728820
Grants
NIH R41 AG074777 (Co-I) 9/30/2021-8/31/2022
NIH R43 AG073040 (Co-I) 8/15/2021-7/31/2022
NIH R01 AG066806 (Co-I) 5/1/2020-1/31/2025
Professional Societies
Society for Neuroscience
Society of Toxicology
Other Experience
Ad-hoc reviewer
NIH study section
Ad-hoc reviewer
Alzheimer's Association
Reviewing editor
Cerebral Cortex and Cerebral Cortex Communications
Graduate Programs
Environmental Health Sciences
Environmental Toxicology
Research Centers
Institute for Memory Impairments and Neurological Disorders (UCI MIND)
UCI Center for Neural Circuit Mapping (CNCM)
Last updated
05/31/2022