Public Health Research Institute Center
UMDNJ - New Jersey Medical School
225 Warren Street
Newark, New Jersey 07103

Phone: (973) 854-3265
Fax: (973) 854-3101
e-mail: changth@umdnj.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.

Role of 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. This program is funded by NIH.

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. In contrast to CD4+ T cells, macrophages are resistant to HIV-induced killing and have long lifespan. Indeed, macrophages appear to provide an important reservoir and to sustain high virus loads after depletion of CD4+ T cells in AIDS patients and in highly pathogenic SHIV-infected rhesus macaques. More importantly, macrophages are the major source of HIV during opportunistic infections that occur more frequently during the advanced stages of AIDS. 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 recently 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. This program is funded by NIH.




Selected Publications

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





C.V.

Please follow this link to download a PDF copy of Theresa Chang's CV.