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Jay Rappaport, PhDJay Rappaport, PhD

 

Associate Chairperson, Department of Neuroscience

Director of Graduate Programs, Department of Neuroscience

Professor, Neuroscience

Professor, Neurovirology

Location: Room 746 MERB

Telephone:  215-707-6248

Fax:  215-707-4888

Email: jayrapp@temple.edu

 

Department of Neuroscience

Center for Neurovirology

 

Educational Background:

 

BA, Biology - 1979

University of Pennsylvania

Philadelphia, PA

 

PhD, Microbiology - 1986

University of Pennsylvania

Philadelphia, PA

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Research Interests:

 

Research Interests:

  • Immuno-pathogenesis of HIV infection and the development of therapeutics for the treatment of AIDS.
  • The role of altered monocyte/macrophage homeostasis in the immunopathogenesis of AIDS and the development of HIV associated dementia.

Research Summary:


Our laboratory is interested in studying the role of certain cells of the innate immune system, monocyte/macrophages, in the pathogenesis of HIV infection. Studies are in progress to identify the role of altered monocyte/macrophage homeostasis in contributing to immune dysfunction in AIDS. Using a simian immunodeficiency virus infection model in non-human primates, we are investigating the molecular and cellular mechanisms involved in dysregulation of monocyte/macrophage homeostasis, immune dysfunction, and the role of altered monocyte/macrophage trafficking in the development of AIDS induced CNS disorders. We are also using this model to determine the effects of opioid drugs of abuse in disease pathogenesis in this model. We are further investigating the effects of opioids on the invasion of virus into the brain and the impact on the development of CNS disease. Studies are now in progress with the goal of developing novel, target-based approaches, to inhibit HIV infection in macrophages, destabilize HIV infected monocyte/macrophage reservoirs, and thereby restore immune function in the setting of AIDS.


Pathogenesis of HIV Associated Dementia Complex/HIV Encephalitis
HIV infection, particularly during the latter stages of disease (AIDS), is accompanied by an increase in the number of activated monocytes in circulation. These cells are often infected by HIV and can invade the CNS leading to neurological disorders. Our current studies are focused on defining the monocyte populations, which are infected by HIV in CNS, and aimed at determining mechanisms responsible for abnormal activation and increased trafficking into organ compartments. It is likely that the mechanisms leading to monocyte activation not only promote CNS disease, but also promote further increases in virus replication and potentially contribute to drug resistant reservoirs in HIV infected patients. Results of our studies in human tissues derived from autopsy specimens demonstrate that the perivascular macrophage is the major reservoir for productive HIV infection in the CNS in HIV encephalitis. In addition, cells with ramified microglial morphology in brain parenchyma are also productively infected. There is a large increase in both populations of macrophages/microglia in HIVE. Having ruled out proliferation as a mechanism for the increased number of these cells, our studies now focus on trafficking of monocyte/macrophages in HIVE. Indeed, other organs including kidney, liver, lymph node and spleen exhibit invasion of monocyte/macrophages in patients with HIVE. Viral genetic analysis of individual cell subsets is currently in progress to determine if HIV evolution is compartmentalized within the CNS or alternatively, if similar viral sequences are found in various organs and tissues.


In order to investigate if altered monocyte/macrophage trafficking is involved in the pathogenesis of HIVE, studies are in progress to investigate the time-course of accumulation, organ invasion and trafficking kinetics in an animal model for HIV induced CNS disease. We are currently investigating alterations in monocyte/ macrophage homeostasis in SIV infected macaques resulting in the expansion of an altered monocyte subset expressing the Fc receptor CD16. We are investigating the rate of production, clearance, as well as the consequent changes in immune polarization. In addition, we are using multiplex and bioinformatics approaches to study a number of candidate genes and biomarkers involved in this process. We are further exploring candidate compounds that may have the capacity to normalize monocyte/macrophage production, differentiation, and activation, with the goal of interfering with the harmful effects of macrophages on the immune system and CNS. This project is in collaboration with Tracy Fischer-Smith and Mark G. Lewis (Bioqual, Inc).

 

Effect of Drugs of Abuse in AIDS Pathogenesis:
In collaboration with Thomas Rogers, Tracy Fischer-Smith, Kamel Khalili, Toby Eisenstein, and Mark Lewis, we are investigating the effect of morphine on the pathogenesis of AIDS in non-human primates. This study should provide information regarding the impact of drugs of abuse on the development of AIDS and CNS disease in humans who are addicted to heroin. These studies involve virologic as well as biologic evaluations including immune and tissue based studies.


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PUBMED PUBLICATIONS :


Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

25026899. Fischer T, Wyatt CM, D'Agati VD, Croul S, McCourt L, Morgello S, Rappaport J, Mononuclear Phagocyte Accumulation in Visceral Tissue in HIV Encephalitis: Evidence for Increased Monocyte/Macrophage Trafficking and Altered Differentiation. Curr HIV Res :()2014 Jul 13

24090653. Cornwell WD, Lewis MG, Fan X, Rappaport J, Rogers TJ, Effect of chronic morphine administration on circulating T cell population dynamics in rhesus macaques. J Neuroimmunol 265:1-2(43-50)2013 Dec 15

23001849. Kogan M, Deshmane S, Sawaya BE, Gracely EJ, Khalili K, Rappaport J, Inhibition of NF-?B activity by HIV-1 Vpr is dependent on Vpr binding protein. J Cell Physiol 228:4(781-90)2013 Apr

22399609. Kogan M, Fischer-Smith T, Kaminsky R, Lehmicke G, Rappaport J, CSF-1R up-regulation is associated with response to pharmacotherapy targeting tyrosine kinase activity in AML cell lines. Anticancer Res 32:3(893-9)2012 Mar

21895511. Kogan M, Haine V, Ke Y, Wigdahl B, Fischer-Smith T, Rappaport J, Macrophage colony stimulating factor regulation by nuclear factor kappa B: a relevant pathway in human immunodeficiency virus type 1 infected macrophages. DNA Cell Biol 31:3(280-9)2012 Mar

21489275. Kogan M, Rappaport J, HIV-1 accessory protein Vpr: relevance in the pathogenesis of HIV and potential for therapeutic intervention. Retrovirology 8:(25)2011 Apr 13

21308746. Maranto J, Rappaport J, Datta PK, Role of C/EBP-ß, p38 MAPK, and MKK6 in IL-1ß-mediated C3 gene regulation in astrocytes. J Cell Biochem 112:4(1168-75)2011 Apr

20890127. Rom I, Darbinyan A, White MK, Rappaport J, Sawaya BE, Amini S, Khalili K, Activation of HIV-1 LTR by Rad51 in microglial cells. Cell Cycle 9:18(3715-22)2010 Sep 15

19204000. Deshmane SL, Mukerjee R, Fan S, Del Valle L, Michiels C, Sweet T, Rom I, Khalili K, Rappaport J, Amini S, Sawaya BE, Activation of the oxidative stress pathway by HIV-1 Vpr leads to induction of hypoxia-inducible factor 1alpha expression. J Biol Chem 284:17(11364-73)2009 Apr 24

18780233. Fischer-Smith T, Bell C, Croul S, Lewis M, Rappaport J, Monocyte/macrophage trafficking in acquired immunodeficiency syndrome encephalitis: lessons from human and nonhuman primate studies. J Neurovirol 14:4(318-26)2008 Aug

18630497. Wang H, White MK, Kaminski R, Darbinian N, Amini S, Johnson EM, Khalili K, Rappaport J, Role of Puralpha in the modulation of homologous recombination-directed DNA repair by HIV-1 Tat. Anticancer Res 28:3A(1441-7)2008 May-Jun

18373432. Fischer-Smith T, Tedaldi EM, Rappaport J, CD163/CD16 coexpression by circulating monocytes/macrophages in HIV: potential biomarkers for HIV infection and AIDS progression. AIDS Res Hum Retroviruses 24:3(417-21)2008 Mar

18247123. Maranto J, Rappaport J, Datta PK, Regulation of complement component C3 in astrocytes by IL-1beta and morphine. J Neuroimmune Pharmacol 3:1(43-51)2008 Mar

18040789. Haine V, Fischer-Smith T, Rappaport J, Macrophage colony-stimulating factor in the pathogenesis of HIV infection: potential target for therapeutic intervention. J Neuroimmune Pharmacol 1:1(32-40)2006 Mar

17722108. Kaminski R, Darbinian N, Sawaya BE, Slonina D, Amini S, Johnson EM, Rappaport J, Khalili K, Darbinyan A, Puralpha as a cellular co-factor of Rev/RRE-mediated expression of HIV-1 intron-containing mRNA. J Cell Biochem 103:4(1231-45)2008 Mar 1

17374989. Wang H, Wang M, Reiss K, Darbinian-Sarkissian N, Johnson EM, Iliakis G, Amini S, Khalili K, Rappaport J, Evidence for the involvement of Puralpha in response to DNA replication stress. Cancer Biol Ther 6:4(596-602)2007 Apr

16978830. Datta PK, Rappaport J, HIV and complement: hijacking an immune defense. Biomed Pharmacother 60:9(561-8)2006 Nov

16940540. Kaniowska D, Kaminski R, Amini S, Radhakrishnan S, Rappaport J, Johnson E, Khalili K, Del Valle L, Darbinyan A, Cross-interaction between JC virus agnoprotein and human immunodeficiency virus type 1 (HIV-1) Tat modulates transcription of the HIV-1 long terminal repeat in glial cells. J Virol 80:18(9288-99)2006 Sep

16741963. Darbinian-Sarkissian N, Czernik M, Peruzzi F, Gordon J, Rappaport J, Reiss K, Khalili K, Amini S, Dysregulation of NGF-signaling and Egr-1 expression by Tat in neuronal cell culture. J Cell Physiol 208:3(506-15)2006 Sep

16321172. Fischer-Smith T, Rappaport J, Evolving paradigms in the pathogenesis of HIV-1-associated dementia. Expert Rev Mol Med 7:27(1-26)2005 Dec 2

16251997. Darbinian-Sarkissian N, Darbinyan A, Otte J, Radhakrishnan S, Sawaya BE, Arzumanyan A, Chipitsyna G, Popov Y, Rappaport J, Amini S, Khalili K, p27(SJ), a novel protein in St John's Wort, that suppresses expression of HIV-1 genome. Gene Ther 13:4(288-95)2006 Feb

16123674. Régulier EG, Panemangalore R, Richardson MW, DeFranco JJ, Kocieda V, Gordon-Lyles DC, Silvera P, Khalili K, Zagury JF, Lewis MG, Rappaport J, Persistent anti-gag, -Nef, and -Rev IgM levels as markers of the impaired functions of CD4+ T-helper lymphocytes during SIVmac251 infection of cynomolgus macaques. J Acquir Immune Defic Syndr 40:1(1-11)2005 Sep 1

15936090. Peruzzi F, Bergonzini V, Aprea S, Reiss K, Sawaya BE, Rappaport J, Amini S, Khalili K, Cross talk between growth factors and viral and cellular factors alters neuronal signaling pathways: implication for HIV-associated dementia. Brain Res Brain Res Rev 50:1(114-25)2005 Dec 1

15710476. Abraham S, Sweet T, Sawaya BE, Rappaport J, Khalili K, Amini S, Cooperative interaction of C/EBP beta and Tat modulates MCP-1 gene transcription in astrocytes. J Neuroimmunol 160:1-2(219-27)2005 Mar

15517862. Darbinian N, White MK, Gallia GL, Amini S, Rappaport J, Khalili K, Interaction between the pura and E2F-1 transcription factors. Anticancer Res 24:5A(2585-94)2004 Sep-Oct

15161643. Fischer-Smith T, Croul S, Adeniyi A, Rybicka K, Morgello S, Khalili K, Rappaport J, Macrophage/microglial accumulation and proliferating cell nuclear antigen expression in the central nervous system in human immunodeficiency virus encephalopathy. Am J Pathol 164:6(2089-99)2004 Jun

15017062. Richardson MW, Hostalek L, Dobson M, Hu J, Shippy R, Siwkowski A, Marmur JD, Khalili K, Klotman PE, Hampel A, Rappaport J, Design, targeting, and initial screening of sTRSV-derived hairpin ribozymes for optimum helix 1 length and catalytic efficiency in vitro. Methods Mol Biol 252:(339-58)2004

14965468. Richardson MW, Sverstiuk AE, Silvera P, Greenhouse J, Lisziewicz J, Lori F, Khalili K, Lewis MG, Rappaport J, T-cell receptor excision circles (TREC) in SHIV 89.6p and SIVmac251 models of HIV-1 infection. DNA Cell Biol 23:1(1-13)2004 Jan

14690854. Régulier EG, Reiss K, Khalili K, Amini S, Zagury JF, Katsikis PD, Rappaport J, T-cell and neuronal apoptosis in HIV infection: implications for therapeutic intervention. Int Rev Immunol 23:1-2(25-59)2004 Jan-Apr

12660540. Richardson MW, Sverstiuk AE, Gracely EJ, Hendel H, Khalili K, Zagury JF, Rappaport J, T-cell receptor excision circles (TREC) and maintenance of long-term non-progression status in HIV-1 infection. AIDS 17:6(915-7)2003 Apr 11

12642031. Richardson MW, Mirchandani J, Duong J, Grimaldo S, Kocieda V, Hendel H, Khalili K, Zagury JF, Rappaport J, Antibodies to Tat and Vpr in the GRIV cohort: differential association with maintenance of long-term non-progression status in HIV-1 infection. Biomed Pharmacother 57:1(4-14)2003 Jan

12504542. Ying Wang J, Peruzzi F, Lassak A, Del Valle L, Radhakrishnan S, Rappaport J, Khalili K, Amini S, Reiss K, Neuroprotective effects of IGF-I against TNFalpha-induced neuronal damage in HIV-associated dementia. Virology 305:1(66-76)2003 Jan 5

12396606. Richardson MW, Mirchandani J, Silvera P, Régulier EG, Capini C, Bojczuk PM, Hu J, Gracely EJ, Boyer JD, Khalili K, Zagury JF, Lewis MG, Rappaport J, Immunogenicity of HIV-1 IIIB and SHIV 89.6P Tat and Tat toxoids in rhesus macaques: induction of humoral and cellular immune responses. DNA Cell Biol 21:9(637-51)2002 Sep

11907220. Silvera P, Richardson MW, Greenhouse J, Yalley-Ogunro J, Shaw N, Mirchandani J, Khalili K, Zagury JF, Lewis MG, Rappaport J, Outcome of simian-human immunodeficiency virus strain 89.6p challenge following vaccination of rhesus macaques with human immunodeficiency virus Tat protein. J Virol 76:8(3800-9)2002 Apr

11704885. Fischer-Smith T, Croul S, Sverstiuk AE, Capini C, L'Heureux D, Régulier EG, Richardson MW, Amini S, Morgello S, Khalili K, Rappaport J, CNS invasion by CD14+/CD16+ peripheral blood-derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirol 7:6(528-41)2001 Dec

11237281. Capini CJ, Richardson MW, Hendel H, Sverstiuk A, Mirchandani J, Régulier EG, Khalili K, Zagury JF, Rappaport J, Autoantibodies to TNFalpha in HIV-1 infection: prospects for anti-cytokine vaccine therapy. Biomed Pharmacother 55:1(23-31)2001 Feb

10878711. Del Valle L, Croul S, Morgello S, Amini S, Rappaport J, Khalili K, Detection of HIV-1 Tat and JCV capsid protein, VP1, in AIDS brain with progressive multifocal leukoencephalopathy. J Neurovirol 6:3(221-8)2000 Jun

10775627. Sawaya BE, Khalili K, Gordon J, Srinivasan A, Richardson M, Rappaport J, Amini S, Transdominant activity of human immunodeficiency virus type 1 Vpr with a mutation at residue R73. J Virol 74:10(4877-81)2000 May

10721459. Richardson MW, Sverstiuk A, Hendel H, Cheung TW, Zagury JF, Rappaport J, Analysis of telomere length and thymic output in fast and slow/non-progressors with HIV infection. Biomed Pharmacother 54:1(21-31)2000 Feb

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