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Scientific Overview Research Interest Summary Principal Investigators    Yuri Bushkin, Ph.D.
   Theresa Chang, Ph.D.
   Neeraj Chauhan, Ph.D.
   Véronique Dartois, Ph.D.
   Thomas Dick, Ph.D.
   Karl Drlica, Ph.D.
   David Dubnau, Ph.D.
   Eliseo A. Eugenin, Ph.D.
   Marila Gennaro, M.D.
   Fred Kramer, Ph.D.
   Barry Kreiswirth, Ph.D.
   Min Lu, Ph.D.
   Leonard Mindich, Ph.D.
   Arkady Mustaev, Ph.D.
   Jyothi Nagajyothi, Ph.D.
   David Perlin, Ph.D.
   Abraham Pinter, Ph.D.
   Marcela Rodriguez, Ph.D.
   Jeanne Salje, Ph.D.
   Lanbo Shi, Ph.D.
   Selvakumar Subbian, Ph.D.
   Sanjay Tyagi, Ph.D.
   Christopher Vinnard, M.D.
   Chaoyang Xue, Ph.D.
   Xilin Zhao, Ph.D.

   Research Faculty
   Liang Chen, Ph.D.
   Eugenie Dubnau, Ph.D.
   Jeanette Hahn, Ph.D.
   Salvatore Marras, Ph.D.
   Yanan Zhao, Ph.D.

Emeritus Faculty Recent Publications
Theresa Li-Yun Chang, Ph.D.

Research Summary  |  Selected Publications  |  C.V.

Public Health Research Institute Center
New Jersey Medical School - Rutgers, The State University of New Jersey
225 Warren Street
Newark, New Jersey 07103

Phone: (973) 854-3265
Fax: (973) 854-3101
e-mail: changth@njms.rutgers.edu

Research Summary

The Chang lab is interested in the role of innate immunity in sexually transmitted infection-mediated enhancement of HIV infection, and HIV infection of human peritoneal macrophages.

Innate immunity in sexually transmitted infection-mediated enhancement of HIV infection
Sexual transmission is the most common route of HIV infection and women account for nearly half of those infected worldwide. Prevention strategies employing different approaches are needed to reduce the probability of transmission. Epidemiologic and clinical studies strongly indicate that sexually transmitted infections (STIs) increase the likelihood of HIV transmission. Although the contribution of STIs to the increase in HIV transmission is likely to be multifaceted, understanding how STIs enhance HIV infection is vital to the development of new strategies for the prevention of HIV. Our program focuses on dissecting the role of innate immunity (e.g defensins and Toll-like receptor activation) in modulation of HIV infection in the setting of STIs. We have shown that induction of human defensins 5 and 6 as well as TLR2 activation enhance HIV infection of various primary cells in response to STIs. The goal of this program is to dissect the underlying molecular mechanisms and to understand the complex function of innate immunity in mucosal transmission of HIV.

Regulation of innate immunity, microbiome and HIV transmission by hormones
Sex hormones modulate immune responses and HIV transmission. We are interested in delineating the mechanism by which sex hormones (estrogen and Depo-Provera) modulate HIV infection/transmission using in vitro and ex vivo models. A recently funded program is to understand the role of Depo-Provera in increased risks of HIV acquisition and transmission. We hypothesize that injectable DMPA alters immune responses and cervicovaginal and colonic microbiomes, which may lead to increased HIV acquisition and transmission. The aims of the Depo-Provera program are designed to (1) determine the impact of Depo-Provera on the systemic and mucosal immune systems and on cervicovaginal and colonic microbiomes in a longitudinal study, and (2) to elucidate the immune mechanisms of MPA-mediated modulation of HIV infection/transmission in vitro, ex vivo and in cervical explant models. The results of our studies will provide a better understanding of how DMPA modulates immunologic responses and microbiomes, thereby informing the design of effective HIV prevention strategies.

HIV-human peritoneal macrophage interaction
Macrophages, one of the major cell types in which HIV can both productively replicate and persist in a latent state, play a crucial role in HIV pathogenesis. Because the long-lived HIV reservoirs constitute a major obstacle to HIV eradication, the aim of this program is to understand the cellular and molecular mechanisms underlying HIV-macrophage interactions, which is essential for developing novel and efficacious therapeutic strategies against HIV infection. We have demonstrated that peritoneal macrophages (PMs) with unique properties are highly abundant in ascitic fluid of patients with cirrhosis, and are susceptible to HIV-1 infection. The project is to dissect the underlying mechanisms of dynamic HIV co-receptor usage in PMs, and to establish the contribution of PMs to HIV reservoirs. The outcome of this study will enhance our understanding of the role of macrophages in HIV pathogenesis and may facilitate discoveries of new strategies for treatment.

Selected Publications

Tasker C, Davidow A, Roche NE, Chang TL (2017) Depot medroxyprogesterone acetate administration alters immune markers for HIV preference and increases susceptibility of peripheral CD4(+) T cells to HIV infection. Immunohorizons 1: 223-235. PMI: 29188238

Couret J, Tasker C, Kim J, Sihvonen T, Fruitwala S, Quayle AJ, Lespinasse P, Heller DS, Chang TL (2017) Differential regulation of IFNalpha, IFNbeta and IFNepsilon gene expression in human cervical epithelial cells. Cell Biosci 7: 57. PMI: 29118969

Tasker C, Subbian S, Gao P, Couret J, Levine C, Ghanny S, Soteropoulos P, Zhao X, Landau N, Lu W, Chang TL (2016) IFN-epsilon protects primary macrophages against HIV infection. JCI Insight 1: e88255. PMI: 27942584

Ren W, Ma Y, Yang L, Gettie A, Salas J, Russell K, Blanchard J, Davidow A, Pei Z, Chang TL, Cheng-Mayer C (2015) Fast disease progression in simian HIV-infected female macaque is accompanied by a robust local inflammatory innate immune and microbial response. AIDS 29: F1-8. PMI: 26035329

Ding J, Tasker C, Lespinasse P, Dai J, Fitzgerald-Bocarsly P, Lu W, Heller D, Chang TL (2015) Integrin alpha4beta7 Expression Increases HIV Susceptibility in Activated Cervical CD4+ T Cells by an HIV Attachment-Independent Mechanism. J Acquir Immune Defic Syndr 69: 509-518. PMI: 26167616

Tasker C, Ding J, Schmolke M, Rivera-Medina A, Garcia-Sastre A, Chang TL (2014) 17beta-estradiol protects primary macrophages against HIV infection through induction of interferon-alpha. Viral Immunol 27: 140-150. PMI: 24801776

Salas JT, Chang TL (2014) Microbiome in human immunodeficiency virus infection. Clin Lab Med 34: 733-745. PMI: 25439273

Aiyar A, Quayle AJ, Buckner LR, Sherchand SP, Chang TL, Zea AH, Martin DH, Belland RJ (2014) Influence of the tryptophan-indole-IFNgamma axis on human genital Chlamydia trachomatis infection: role of vaginal co-infections. Front Cell Infect Microbiol 4: 72. PMI: 24918090

Sperling R, Kraus TA, Ding J, Veretennikova A, Lorde-Rollins E, Singh T, Lo Y, Quayle AJ, Chang TL (2013) Differential profiles of immune mediators and in vitro HIV infectivity between endocervical and vaginal secretions from women with Chlamydia trachomatis infection: a pilot study. J Reprod Immunol 99: 80-87. PMI: 23993451

Ding J, Tasker C, Valere K, Sihvonen T, Descalzi-Montoya DB, Lu W, Chang TL (2013) Anti-HIV activity of human defensin 5 in primary CD4+ T cells under serum-deprived conditions is a consequence of defensin-mediated cytotoxicity. PLoS One 8: e76038. PMI: 24086683

Jarvis GA, Chang TL (2012) Modulation of HIV transmission by Neisseria gonorrhoeae: Molecular and Immunological Aspects. Current HIV research. PMI: 22384840

Ding J, Chang TL (2012) TLR2 activation enhances HIV nuclear import and infection through T cell activation-independent and -dependent pathways. Journal of immunology 188: 992-1001. PMI: 22210918

Rapista A, Ding J, Benito B, Lo YT, Neiditch MB, Lu W, Chang TL (2011) Human defensins 5 and 6 enhance HIV-1 infectivity through promoting HIV attachment. Retrovirology 8: 45. PMI: 21672195

Ding J, Rapista A, Teleshova N, Lu W, Klotman ME, Chang TL (2011) Mucosal human defensins 5 and 6 antagonize the anti-HIV activity of candidate polyanion microbicides. J Innate Immun 3: 208-212. PMI: 21160168

Buckner LR, Schust DJ, Ding J, Nagamatsu T, Beatty W, Chang TL, Greene SJ, Lewis ME, Ruiz B, Holman SL, Spagnuolo RA, Pyles RB, Quayle AJ (2011) Innate immune mediator profiles and their regulation in a novel polarized immortalized epithelial cell model derived from human endocervix. J Reprod Immunol 92: 8-20. PMI: 21943934

Ding J, Rapista A, Teleshova N, Mosoyan G, Jarvis GA, Klotman ME, Chang TL (2010) Neisseria gonorrhoeae enhances HIV-1 infection of primary resting CD4+ T cells through TLR2 activation. J Immunol 184: 2814-2824. PMI: 20147631

Chang TL, Klepper A, Ding J, Garber J, Rapista A, Mosoian A, Hubner W, Gutierrez J, Walewski J, Abergel J, Schiano T, Branch A (2010) Human peritoneal macrophages from ascitic fluid can be infected by a broad range of HIV-1 isolates. J Acquir Immune Defic Syndr 53: 292-302. PMI: 20065862

Ding J, Chou YY, Chang TL (2009) Defensins in viral infections. J Innate Immun 1: 413-420. PMI: 20375599 (2009 most frequently downloaded paper in the journal)

Teleshova N, Chang TL, Profy A, Klotman ME (2008) Inhibitory effect of PRO 2000, a candidate microbicide, on dendritic cell-mediated human immunodeficiency virus transfer. Antimicrob Agents Chemother 52: 1751-1758. PMI: 18332174

Klotman ME, Rapista A, Teleshova N, Micsenyi A, Jarvis GA, Lu W, Porter E, Chang TL (2008) Neisseria gonorrhoeae-induced human defensins 5 and 6 increase HIV infectivity: role in enhanced transmission. J Immunol 180: 6176-6185. PMI: 18424739

Salvatore M, Garcia-Sastre A, Ruchala P, Lehrer RI, Chang TL, Klotman ME (2007) alpha-Defensin inhibits influenza virus replication by cell-mediated mechanism(s). J Infect Dis 196: 835-843. PMI: 17703413

Chang TL, Teleshova N, Rapista A, Paluch M, Anderson RA, Waller DP, Zaneveld LJ, Granelli-Piperno A, Klotman ME (2007) SAMMA, a mandelic acid condensation polymer, inhibits dendritic cell-mediated HIV transmission. FEBS Lett 581: 4596-4602. PMI: 17825297

Liu X, Mosoian A, Chang TL, Zerhouni-Layachi B, Snyder A, Jarvis GA, Klotman ME (2006) Gonococcal lipooligosaccharide suppresses HIV infection in human primary macrophages through induction of innate immunity. J Infect Dis 194: 751-759. PMI: 16941340

Klotman ME, Chang TL (2006) Defensins in innate antiviral immunity. Nat Rev Immunol 6: 447-456. PMI: 16724099

Chang TL, Vargas J, Jr., DelPortillo A, Klotman ME (2005) Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest 115: 765-773. PMI: 15719067


BS, Sooshow University, Taiwan
MS. Auburn University, AL
PhD. New York University, NY
Postdoc: Yale University, CT, and Aaron Diamond AIDS Research Center, Rockefeller University, NY

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