Faculty

Back to Index
Terrence Christopher Town, PhD
Visiting Professor of Physiology & Biophysics
Zilkha Neurogenetic Institute
ZNI 321 1501 San Pablo Street Health Sciences Campus Los Angeles
+1 323 442 2492

Overview

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.

Publications

Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease. J Vis Exp. 2016 Dec 26; (118). View in: PubMed

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

Targeting innate immunity for neurodegenerative disorders of the central nervous system. J Neurochem. 2016 Sep; 138(5):653-93. View in: PubMed

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

Innate Immunity Fights Alzheimer's Disease. Trends Neurosci. 2015 Nov; 38(11):674-81. View in: PubMed

The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive? Brain Res. The role of the immune system in neurodegenerative disorders: Adaptive or maladaptive? Brain Res. 2015 Aug 18; 1617:155-73. View in: PubMed

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

Spatial proximity of homologous alleles and long noncoding RNAs regulate a switch in allelic gene expression. Proc Natl Acad Sci U S A. 2015 Mar 31; 112(13):E1577-86. View in: PubMed

Il10 deficiency rebalances innate immunity to mitigate Alzheimer-like pathology. Neuron. 2015 Feb 4; 85(3):534-48. 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

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

T-cell TGF-ß signaling abrogation restricts medulloblastoma progression. Proc Natl Acad Sci U S A. 2014 Aug 19; 111(33):E3458-66. View in: PubMed

MyD88 Is Dispensable for Cerebral Amyloidosis and Neuroinflammation in APP/PS1 Transgenic Mice. Am J Pathol. 2014; 184(11):2855-61. 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

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

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

Tannic acid is a natural ß-secretase inhibitor that prevents cognitive impairment and mitigates Alzheimer-like pathology in transgenic mice. J Biol Chem. 2012 Feb 24; 287(9):6912-27. 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

Rapid genetic targeting of pial surface neural progenitors and immature neurons by neonatal electroporation. Neural Dev. 2012; 7:26. 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 28; 475(7357):514-8. View in: PubMed

The role of LAT in increased CD8+ T cell exhaustion in trigeminal ganglia of mice latently infected with herpes simplex virus 1. J Virol. 2011 May; 85(9):4184-97. 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

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. 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

Targeting S100B in Cerebral Ischemia and in Alzheimer's Disease. Cardiovasc Psychiatry Neurol. 2010; 2010. View in: PubMed

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease? J Neuroimmune Pharmacol. 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. 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

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

Toll-like receptor 7 mitigates lethal West Nile encephalitis via interleukin 23-dependent immune cell infiltration and homing. Immunity. 2009 Feb 20; 30(2):242-53. View in: PubMed

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

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

Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling. Proc Natl Acad Sci U S A. 2008 Sep 2; 105(35):13127-32. View in: PubMed

TGF-beta signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2008 Aug 5; 105(31):10865-70. View in: PubMed

Drak2 contributes to West Nile virus entry into the brain and lethal encephalitis. J Immunol. 2008 Aug 1; 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

Defective p53 engagement after the induction of DNA damage in cells deficient in topoisomerase 3beta. Proc Natl Acad Sci U S A. 2008 Apr 1; 105(13):5063-8. 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

The stumpy gene is required for mammalian ciliogenesis. Proc Natl Acad Sci U S A. 2008 Feb 26; 105(8):2853-8. View in: PubMed

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

West Nile virus envelope protein inhibits dsRNA-induced innate immune responses. J Immunol. 2007 Dec 15; 179(12):8403-9. View in: PubMed

Toll-like receptor modulation of murine cerebral malaria is dependent on the genetic background of the host. J Infect Dis. 2007 Nov 15; 196(10):1553-64. 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

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

Transcutaneous beta-amyloid immunization reduces cerebral beta-amyloid deposits without T cell infiltration and microhemorrhage. Proc Natl Acad Sci U S A. 2007 Feb 13; 104(7):2507-12. 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

The microglial "activation" continuum: from innate to adaptive responses. J Neuroinflammation. 2005 Oct 31; 2:24. 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

Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation. J Neurosci. 2005 Jun 8; 25(23):5533-43. View in: PubMed

Interchromosomal associations between alternatively expressed loci. Nature. 2005 Jun 2; 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

T-cells in Alzheimer's disease. Neuromolecular Med. 2005; 7(3):255-64. View in: PubMed

Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat Med. 2004 Dec; 10(12):1366-73. 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

Role of CD40 ligand in amyloidosis in transgenic Alzheimer's mice. Nat Neurosci. 2002 Dec; 5(12):1288-93. View in: PubMed

Reduced Th1 and enhanced Th2 immunity after immunization with Alzheimer's beta-amyloid(1-42). J Neuroimmunol. 2002 Nov; 132(1-2):49-59. 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 1; 69(3):362-72. View in: PubMed

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

Powered bySC CTSI