In response to RFA HD-OO-006, """"""""Women's HIV Pathogenesis Program"""""""", we propose a multidisciplinary program comprised of four interactive research projects and three supporting cores that thematically seeks to explore biological aspects of HIV infection and pathogenesis that are unique to women. Project I, led by Warner Greene, will study the molecular and cellular basis for HIV infection in the female genital tract using a cervical-vaginal organ culture model coupled with the use of fluorescently labeled virions to monitor the cellular targets and evolution of infection within this mucosal tissue. This project will also investigate the potential function of HIV Vpr as a transcriptional coactivator of the estrogen and progesterone nuclear hormone receptors and study the biological consequences of such a virus-host transcription factor interplay on HIV gene expression. Project II, led by Robert Grant, will explore whether the viral quasi-species present in the female genital tract of HIV infected women differs from that simultaneously circulating in the blood both prior to and after the administration of potent antiviral therapy. Other studies will assess potential defects in the ability of protease inhibitor resistant viruses to infect macrophages and dendritic cells. Project III, led by Marc Hellerstein, will examine the influence of sex hormones on T-helper cell turnover measured by a combination of flow based cell isolation and mass spectroscopy following deuterated glucose or 2H20 labeling in vivo. These studies will involve the analysis of hypogonadal women and men, postmenopausal women before and after estrogen replacement therapy, and children before and after puberty. Project IV, led by Leslie Benet, will determine the effect of hormonal changes occurring within the ovulatory cycle, during menopause, and after estrogen replacement on P-glycoprotein exporter and cytochrome p450 3A enzyme expression and functional activity. Changes in these two proteins will be monitored in the intestine, endometrium and PBMCs. This project will also assess how changes in these proteins may affect the response to HIV protease inhibitors that are all substrates for both proteins. Core A, led by Ruth Greenblatt. will provide clinical coordination of these projects, including recruitment, study visits, participant tracking and compensation. Core B, led by Robert Taylor, will provide reproductive endocrinology consultation, gonadal function assessments and ovulatory cycle staging, and tissue collection. Core C led by Warner Greene will provide overall scientific leadership, data entry and biostatistical analysis for all projects, and administrative support coupled with fiscally sound budget management. Together, these projects and cores combine to form a program that promises to yield new insights into the unique features that underlie gender specific differences in HIV infection and pathogenesis.
| Chan, Jonathan K; Bhattacharyya, Darshana; Lassen, Kara G et al. (2013) Calcium/calcineurin synergizes with prostratin to promote NF-?B dependent activation of latent HIV. PLoS One 8:e77749 |
| Chan, Jonathan K L; Greene, Warner C (2011) NF-ýýB/Rel: agonist and antagonist roles in HIV-1 latency. Curr Opin HIV AIDS 6:12-8 |
| Ghotb, Alireza; Noworolski, Susan M; Madden, Erin et al. (2010) Adipose tissue and metabolic factors associated with steatosis in HIV/HCV coinfection: histology versus magnetic resonance spectroscopy. J Acquir Immune Defic Syndr 55:228-31 |
| Roan, Nadia R; Sowinski, Stefanie; Münch, Jan et al. (2010) Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer of viral infection). J Biol Chem 285:1861-9 |
| Noworolski, Susan M; Tien, Phyllis C; Merriman, Raphael et al. (2009) Respiratory motion-corrected proton magnetic resonance spectroscopy of the liver. Magn Reson Imaging 27:570-6 |
| Rahangdale, Lisa; Greenblatt, Ruth M; Perry, Jean et al. (2009) In vivo effects of nonoxynol-9 on endometrial immune cell populations. J Acquir Immune Defic Syndr 52:137-9 |
| Weiss, Gerson; Goldsmith, Laura T; Taylor, Robert N et al. (2009) Inflammation in reproductive disorders. Reprod Sci 16:216-29 |
| Chiu, Ya-Lin; Greene, Warner C (2009) APOBEC3G: an intracellular centurion. Philos Trans R Soc Lond B Biol Sci 364:689-703 |
| Cavrois, Marielle; Neidleman, Jason; Greene, Warner C (2008) The achilles heel of the trojan horse model of HIV-1 trans-infection. PLoS Pathog 4:e1000051 |
| Chiu, Ya-Lin; Greene, Warner C (2008) The APOBEC3 cytidine deaminases: an innate defensive network opposing exogenous retroviruses and endogenous retroelements. Annu Rev Immunol 26:317-53 |
Showing the most recent 10 out of 34 publications
