Terrence Christopher Town
Terrence Christopher Town
Zilkha Neurogenetic Institute
ZNI 321, 1501 San Pablo Street Health Sciences Campus Los Angeles
The Town lab joined the Zilkha Neurogenetic Institute on May 1, 2013. My lab's focus is to develop a treatment for Alzheimer's disease by targeting the body's immune system. Most therapies targeting the disease are thwarted by the blood-brain barrier, a natural mechanism that protects brain cells from entry of peripheral substances, and by the fact that immune responses in the brain are typically muted. However, in laboratory mice programmed to develop Alzheimer's-like disease, my group has shown that certain immune cells can be coaxed into the brain from the circulation, where they attack the damaging sticky plaque buildup that is a defining feature of Alzheimer's disease.

My lab is continuing to pursue this line of research in hopes of developing a next-generation drug for Alzheimer's disease. This work, which has been funded by the National Institutes of Health, the Alzheimer's Association, and the American Federation for Aging Research, has been published in numerous high-impact peer-reviewed journals including Science, Nature, Nature Medicine, Nature Neuroscience, Immunity, Neuron, PNAS, Trends in Neurosciences, and The Journal of Neuroscience.

My lab revolutionized the field of Alzheimer's disease research by generating the first rat model of the disease that manifests all of the clinico-pathological hallmarks of the human syndrome. Specifically, we made transgenic rats that over-express two mutant human transgenes that are each independently causative of autosomal dominant Alzheimer's disease: "Swedish" mutant amyloid precursor protein and deltaE9 mutant presenilin-1. Unlike their transgenic mouse cousins that develop "senile" plaques but fail to manifest "tangles" and frank neuronal loss, these transgenic rats-for the first time-develop the full spectrum of Alzheimer pathologies. This makes them an invaluable tool for understanding Alzheimer's disease etiology and for pre-clinical testing of cutting-edge therapeutics.

Combined treatment with the phenolics (-)-epigallocatechin-3-gallate and ferulic acid improves cognition and reduces Alzheimer-like pathology in mice J Biol Chem. 2019 02 22; 294(8):2714-2731. . View in PubMed

Let's make microglia great again in neurodegenerative disorders J Neural Transm (Vienna). 2018 05; 125(5):751-770. . View in PubMed

Bi-directional Association of Cerebrospinal Fluid Immune Markers with Stage of Alzheimer's Disease Pathogenesis J Alzheimers Dis. 2018; 63(2):577-590. . View in PubMed

Combination therapy with octyl gallate and ferulic acid improves cognition and neurodegeneration in a transgenic mouse model of Alzheimer's disease J Biol Chem. 2017 07 07; 292(27):11310-11325. . View in PubMed

Interleukin-17A Promotes CD8+ T Cell Cytotoxicity To Facilitate West Nile Virus Clearance J Virol. 2017 Jan 01; 91(1). . View in PubMed

Interrelationship of Primary Virus Replication, Level of Latency, and Time to Reactivation in the Trigeminal Ganglia of Latently Infected Mice J Virol. 2016 10 15; 90(20):9533-42. . View in PubMed

Amyloid Cascade into Clarity Immunity. 2016 10 18; 45(4):717-718. . View in PubMed

Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma Cell Rep. 2016 12 20; 17(12):3407. . View in PubMed

CD8+ T Cells Play a Bystander Role in Mice Latently Infected with Herpes Simplex Virus 1 J Virol. 2016 05 15; 90(10):5059-5067. . View in PubMed

Innate Immunity Fights Alzheimer's Disease Trends Neurosci. 2015 Nov; 38(11):674-681. . View in PubMed

Neuroinflammation in Alzheimer's disease Lancet Neurol. 2015 Apr; 14(4):388-405. . View in PubMed

Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology Neuron. 2015 Feb 04; 85(3):534-48. . View in PubMed

Multi-Shell Hybrid Diffusion Imaging (HYDI) at 7 Tesla in TgF344-AD Transgenic Alzheimer Rats PLoS One. 2015; 10(12):e0145205. . View in PubMed

Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection PLoS Pathog. 2015; 11(11):e1005292. . View in PubMed

Characterization of cancer stem cells and primary cilia in medulloblastoma CNS Neurol Disord Drug Targets. 2015; 14(5):600-11. . View in PubMed

MyD88 is dispensable for cerebral amyloidosis and neuroinflammation in APP/PS1 transgenic mice Am J Pathol. 2014 Nov; 184(11):2855-61. . View in PubMed

Methylene blue modulates ß-secretase, reverses cerebral amyloidosis, and improves cognition in transgenic mice J Biol Chem. 2014 Oct 31; 289(44):30303-17. . View in PubMed

CD8a dendritic cells drive establishment of HSV-1 latency PLoS One. 2014; 9(4):e93444. . View in PubMed

Innate immunity in Alzheimer's disease: a complex affair CNS Neurol Disord Drug Targets. 2013 Aug; 12(5):593-607. . View in PubMed

A transgenic Alzheimer rat with plaques, tau pathology, behavioral impairment, oligomeric aß, and frank neuronal loss J Neurosci. 2013 Apr 10; 33(15):6245-56. . View in PubMed

Increasing hematopoietic stem cell yield to develop mice with human immune systems Biomed Res Int. 2013; 2013:740892. . View in PubMed

Ferulic acid is a nutraceutical ß-secretase modulator that improves behavioral impairment and alzheimer-like pathology in transgenic mice PLoS One. 2013; 8(2):e55774. . View in PubMed

Brain injury, neuroinflammation and Alzheimer's disease Front Aging Neurosci. 2013; 5:26. . View in PubMed

Basic biology and mechanisms of neural ciliogenesis and the B9 family Mol Neurobiol. 2012 Jun; 45(3):564-70. . View in PubMed

Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis Immunity. 2012 Mar 23; 36(3):401-14. . View in PubMed

Microglia in Alzheimer's Disease: It's All About Context Int J Alzheimers Dis. 2012; 2012:314185. . View in PubMed

IL-22 signaling contributes to West Nile encephalitis pathogenesis PLoS One. 2012; 7(8):e44153. . View in PubMed

Adaptive and innate transforming growth factor beta signaling impact herpes simplex virus 1 latency and reactivation J Virol. 2011 Nov; 85(21):11448-56. . View in PubMed

Myeloid differentiation factor-2 interacts with Lyn kinase and is tyrosine phosphorylated following lipopolysaccharide-induced activation of the TLR4 signaling pathway J Immunol. 2011 Oct 15; 187(8):4331-7. . View in PubMed

Control of TH17 cells occurs in the small intestine Nature. 2011 Jul 17; 475(7357):514-8. . View in PubMed

Macrophage IL-12p70 signaling prevents HSV-1-induced CNS autoimmunity triggered by autoaggressive CD4+ Tregs Invest Ophthalmol Vis Sci. 2011 Apr; 52(5):2321-33. . View in PubMed

How to get from here to there: macrophage recruitment in Alzheimer's disease Curr Alzheimer Res. 2011 Mar; 8(2):156-63. . View in PubMed

Mutant presenilin-1 deregulated peripheral immunity exacerbates Alzheimer-like pathology J Cell Mol Med. 2011 Feb; 15(2):327-38. . View in PubMed

CD45 deficiency drives amyloid-ß peptide oligomers and neuronal loss in Alzheimer's disease mice J Neurosci. 2011 Jan 26; 31(4):1355-65. . View in PubMed

Macrophages in Alzheimer's disease: the blood-borne identity J Neural Transm (Vienna). 2010 Aug; 117(8):961-70. . View in PubMed

Alzheimer's Disease Beyond Abeta Expert Rev Neurother. 2010 May; 10(5):671-5. . View in PubMed

Inflammation, immunity, and Alzheimer's disease CNS Neurol Disord Drug Targets. 2010 Apr; 9(2):129-31. . View in PubMed

Overexpression of human S100B exacerbates cerebral amyloidosis and gliosis in the Tg2576 mouse model of Alzheimer's disease Glia. 2010 Feb; 58(3):300-14. . View in PubMed

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease? J Neuroimmune Pharmacol. 2009 Dec; 4(4):462-75.. View in PubMed

Can peripheral leukocytes be used as Alzheimer's disease biomarkers? Expert Rev Neurother. 2009 Nov; 9(11):1623-33.. View in PubMed

IL-10 signaling blockade controls murine West Nile virus infection PLoS Pathog. 2009 Oct; 5(10):e1000610. . View in PubMed

A protective function for interleukin 17A in T cell-mediated intestinal inflammation Nat Immunol. 2009 Jun; 10(6):603-9. . View in PubMed

A role for the JAK-STAT1 pathway in blocking replication of HSV-1 in dendritic cells and macrophages Virol J. 2009 May 13; 6:56. . View in PubMed

Alternative Abeta immunotherapy approaches for Alzheimer's disease CNS Neurol Disord Drug Targets. 2009 Apr; 8(2):114-27. . View in PubMed

Flavonoid-mediated presenilin-1 phosphorylation reduces Alzheimer's disease beta-amyloid production J Cell Mol Med. 2009 Mar; 13(3):574-88. . View in PubMed

Approaches to determine expression of inflammatory cytokines Methods Mol Biol. 2009; 511:107-42. . View in PubMed

Inflammaging as a prodrome to Alzheimer's disease J Neuroinflammation. 2008 Nov 11; 5:51. . View in PubMed

Drak2 contributes to West Nile virus entry into the brain and lethal encephalitis J Immunol. 2008 Aug 01; 181(3):2084-91. . View in PubMed

Overexpression of human S100B exacerbates brain damage and periinfarct gliosis after permanent focal ischemia Stroke. 2008 Jul; 39(7):2114-21. . View in PubMed

Peripherally administered human umbilical cord blood cells reduce parenchymal and vascular beta-amyloid deposits in Alzheimer mice Stem Cells Dev. 2008 Jun; 17(3):423-39. . View in PubMed

Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology Nat Med. 2008 Jun; 14(6):681-7. . View in PubMed

Icam-1 participates in the entry of west nile virus into the central nervous system J Virol. 2008 Apr; 82(8):4164-8. . View in PubMed

Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3beta Proc Natl Acad Sci U S A. 2008 Apr 01; 105(13):5063-8. . View in PubMed

CD40L disruption enhances Abeta vaccine-mediated reduction of cerebral amyloidosis while minimizing cerebral amyloid angiopathy and inflammation Neurobiol Dis. 2008 Feb; 29(2):336-53. . View in PubMed

Apoptotic hepatocyte DNA inhibits hepatic stellate cell chemotaxis via toll-like receptor 9 Hepatology. 2007 Nov; 46(5):1509-18. . View in PubMed

Control of toll-like receptor 7 expression is essential to restrict autoimmunity and dendritic cell proliferation Immunity. 2007 Nov; 27(5):801-10. . View in PubMed

Abrogation of macrophage migration inhibitory factor decreases West Nile virus lethality by limiting viral neuroinvasion J Clin Invest. 2007 Oct; 117(10):3059-66. . View in PubMed

Antiviral peptides targeting the west nile virus envelope protein J Virol. 2007 Feb; 81(4):2047-55. . View in PubMed

NSAIDs for the chemoprevention of Alzheimer's disease Subcell Biochem. 2007; 42:229-48. . View in PubMed

HSP70 enhances macrophage phagocytosis by interaction with lipid raft-associated TLR-7 and upregulating p38 MAPK and PI3K pathways J Surg Res. 2006 Nov; 136(1):58-69. . View in PubMed

Arundic Acid ameliorates cerebral amyloidosis and gliosis in Alzheimer transgenic mice J Pharmacol Exp Ther. 2006 Aug; 318(2):571-8. . View in PubMed

ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate-induced alpha-secretase cleavage of amyloid precursor protein J Biol Chem. 2006 Jun 16; 281(24):16419-27. . View in PubMed

Microglia recognize double-stranded RNA via TLR3 J Immunol. 2006 Mar 15; 176(6):3804-12. . View in PubMed

Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice J Neurosci. 2005 Sep 21; 25(38):8807-14. . View in PubMed

Interchromosomal associations between alternatively expressed loci Nature. 2005 Jun 02; 435(7042):637-45. . View in PubMed

Modulation of astrocytic activation by arundic acid (ONO-2506) mitigates detrimental effects of the apolipoprotein E4 isoform after permanent focal ischemia in apolipoprotein E knock-in mice J Cereb Blood Flow Metab. 2005 Jun; 25(6):748-62. . View in PubMed

CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid beta-peptide Eur J Immunol. 2005 Mar; 35(3):901-10. . View in PubMed

Behavioral effects of CD40-CD40L pathway disruption in aged PSAPP mice Brain Res. 2004 Jul 23; 1015(1-2):161-8. . View in PubMed

Augmented delayed infarct expansion and reactive astrocytosis after permanent focal ischemia in apolipoprotein E4 knock-in mice J Cereb Blood Flow Metab. 2004 Jun; 24(6):646-56. . View in PubMed

CD45 isoform RB as a molecular target to oppose lipopolysaccharide-induced microglial activation in mice Neurosci Lett. 2004 May 13; 362(1):26-30. . View in PubMed

Neuronal expression of CD22: novel mechanism for inhibiting microglial proinflammatory cytokine production Glia. 2004 May; 46(4):369-79. . View in PubMed

Increased vulnerability to focal ischemic brain injury in human apolipoprotein E4 knock-in mice J Neuropathol Exp Neurol. 2003 Mar; 62(3):280-91. . View in PubMed

CD45 isoform alteration in CD4+ T cells as a potential diagnostic marker of Alzheimer's disease J Neuroimmunol. 2002 Nov; 132(1-2):164-72. . View in PubMed

CD40-CD40L interaction in Alzheimer's disease Curr Opin Pharmacol. 2002 Aug; 2(4):445-51. . View in PubMed

p35/Cdk5 pathway mediates soluble amyloid-beta peptide-induced tau phosphorylation in vitro J Neurosci Res. 2002 Aug 01; 69(3):362-72. . View in PubMed

Confirmation of association between D10S583 and Alzheimer's disease in a case--control sample Neurosci Lett. 2002 Jun 07; 325(2):87-90. . View in PubMed

CD40 is expressed and functional on neuronal cells EMBO J. 2002 Feb 15; 21(4):643-52. . View in PubMed

A functional polymorphism within the mu-opioid receptor gene and risk for abuse of alcohol and other substances Mol Psychiatry. 2002; 7(2):224-8. . View in PubMed

CD40 signaling and Alzheimer's disease pathogenesis Neurochem Int. 2001 Nov-Dec; 39(5-6):371-80. . View in PubMed

Cholesterol accumulates in senile plaques of Alzheimer disease patients and in transgenic APP(SW) mice J Neuropathol Exp Neurol. 2001 Aug; 60(8):778-85. . View in PubMed

Characterization of murine immunoglobulin G antibodies against human amyloid-beta1-42 Neurosci Lett. 2001 Jul 13; 307(2):101-4. . View in PubMed

Intracisternal increase of superoxide anion production in a canine subarachnoid hemorrhage model Stroke. 2001 Mar; 32(3):636-42. . View in PubMed

CD45 inhibits CD40L-induced microglial activation via negative regulation of the Src/p44/42 MAPK pathway J Biol Chem. 2000 Nov 24; 275(47):37224-31. . View in PubMed

CD45 opposes beta-amyloid peptide-induced microglial activation via inhibition of p44/42 mitogen-activated protein kinase J Neurosci. 2000 Oct 15; 20(20):7587-94. . View in PubMed

Cholesterol modulates vascular reactivity to endothelin-1 by stimulating a pro-inflammatory pathway Biochem Biophys Res Commun. 2000 Aug 02; 274(2):553-8. . View in PubMed

beta-Amyloid vasoactivity and proinflammation in microglia can be blocked by cGMP-elevating agents Ann N Y Acad Sci. 2000 Apr; 903:446-50. . View in PubMed

A beta vasoactivity: an inflammatory reaction Ann N Y Acad Sci. 2000 Apr; 903:97-109. . View in PubMed

Novel strategies for opposing murine microglial activation Neurosci Lett. 2000 Jan 07; 278(1-2):5-8. . View in PubMed

Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation Science. 1999 Dec 17; 286(5448):2352-5. . View in PubMed

Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10 J Immunol. 1999 Dec 15; 163(12):6614-21. . View in PubMed

Association of a functional mu-opioid receptor allele (+118A) with alcohol dependency Am J Med Genet. 1999 Oct 15; 88(5):458-61. . View in PubMed

Alzheimers disease is not associated with the hypertension genetic risk factors PLA(2) or G protein beta3, either independently or interactively with apolipoprotein E Am J Med Genet. 1999 Oct 15; 88(5):465-8. . View in PubMed

Induction of CD40 on human endothelial cells by Alzheimer's beta-amyloid peptides Brain Res Bull. 1999 Sep 15; 50(2):143-8. . View in PubMed

Bcl-X(L) inhibits apoptosis and necrosis produced by Alzheimer's beta-amyloid1-40 peptide in PC12 cells Neurosci Lett. 1999 Sep 03; 272(1):5-8. . View in PubMed

Activation of microglial cells by the CD40 pathway: relevance to multiple sclerosis J Neuroimmunol. 1999 Jun 01; 97(1-2):77-85. . View in PubMed

No genetic association between polymorphisms in the Tau gene and Alzheimer's disease in clinic or population based samples Neurosci Lett. 1999 May 14; 266(3):193-6. . View in PubMed

Inhibition of Alzheimer's beta-amyloid induced vasoactivity and proinflammatory response in microglia by a cGMP-dependent mechanism Exp Neurol. 1999 May; 157(1):211-21. . View in PubMed

Isoform-specific vasoconstriction induced by apolipoprotein E and modulation of this effect by Alzheimer's beta-amyloid peptide Neurosci Lett. 1998 Nov 06; 256(2):73-6. . View in PubMed

No association between the low density lipoprotein receptor-related protein (LRP) gene and late-onset Alzheimer's disease in a community-based sample Neurosci Lett. 1997 Sep 19; 233(2-3):145-7. . View in PubMed

Lack of association between the apolipoprotein E epsilon4 allele (APOE epsilon4) and chronic schizophrenia Am J Med Genet. 1997 Jul 25; 74(4):451-2. . View in PubMed

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