This proposal is being submitted to the NIDCR PAR-05-031, """"""""Multidisciplinary Research on Oral Manifestations Associated with HIV/AIDS"""""""". Our proposal, """"""""Crosstalk among oral and gastrointestinal soluble innate factors, HIV and microbes"""""""" is being submitted by NYU College of Dentistry (NYUCD), with Dr. Daniel Malamud as principal investigator. Dr. Malamud has assembled a talented group of investigators for NYUCD, NYU School of Medicine (NYUSoM) and the Aaron Diamond AIDS Research Center (ADARC), all located within a few blocks of each other on First Avenue in New York City. The proposal consists of 4 interrelated research projects, an Administrative/Biostatistical Core and a Clinical Core. The entire proposal utilizes the same case controlled study population consisting of 85 HIV+, HAART naive subjects who will subsequently begin antiretroviral therapy. There will also be a similar cohort of HIV- subjects. The clinical core will obtain oral and Gl samples, monitor patient progress, carry out complete oral health examinations, and maintain all subject records. Project 1 (Dr. Linqi Zhang, ADARC) will determine the whole saliva proteome comparing HIV-, HIV+/HAART naive, and HIV+ post-HAART samples. Studies will focus on soluble molecules that are part of the host innate defense system. Project 2 (Dr Yihong Li, NYUCD) will define the oral microbiota in HIV vs. HIV+ saliva samples and HIV+ before and after HAART. Studies will focus on overall microbial diversity, and quantitation of bacteria that are altered after HIV infection, and/or related to caries and periodontal disease. Project 3 (Dr. Michael Poles, NYUSoM) will study the remainder of the Gl track using endoscopy to obtain fluid and biopsy samples. His study will focus in innate immune mediators and Gl microbes, and his data compared to Projects 1 and 2. Project 4 (Dr. Daniel Malamud, NYUCD) will study antibacterial and antiviral activities in saliva, focusing on the innate host defense system. In addition he will determine the ability to infect buccal vs. rectal tissue in vitro, and compare the HIV-1 variants obtained from oral, Gl and blood. The Administrative/Biostatistical Core (Drs. Malamud and Norman) will oversee the entire study via an Executive Committee and an External Advisory Committee. All data and statistical analyses will be handled by this core. The overall goal is to define the interactions between host defense molecules and bacteria in HIV infection and subsequent antiretroviral therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19DE018385-03
Application #
7668040
Study Section
Special Emphasis Panel (ZDE1-PZ (23))
Program Officer
Rodriguez-Chavez, Isaac R
Project Start
2007-08-01
Project End
2012-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
3
Fiscal Year
2009
Total Cost
$1,282,604
Indirect Cost
Name
New York University
Department
Other Basic Sciences
Type
Schools of Dentistry
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
Yang, Liying; Poles, Michael A; Fisch, Gene S et al. (2016) HIV-induced immunosuppression is associated with colonization of the proximal gut by environmental bacteria. AIDS 30:19-29
Patyka, Mariia; Malamud, Daniel; Weissman, Drew et al. (2015) Periluminal Distribution of HIV-Binding Target Cells and Gp340 in the Oral, Cervical and Sigmoid/Rectal Mucosae: A Mapping Study. PLoS One 10:e0132942
Phelan, Joan A; Abrams, William R; Norman, Robert G et al. (2014) Design aspects of a case-control clinical investigation of the effect of HIV on oral and gastrointestinal soluble innate factors and microbes. PLoS One 9:e112901
Li, Yihong; Saxena, Deepak; Chen, Zhou et al. (2014) HIV infection and microbial diversity in saliva. J Clin Microbiol 52:1400-11
Barber, Cheryl; Weissman, Drew; Barnhart, Kurt et al. (2013) An electrochemiluminescence assay for gp340 (DMBT1). Anal Biochem 440:78-80
Zhang, Nawei; Zhang, Zhenyu; Feng, Shan et al. (2013) Quantitative analysis of differentially expressed saliva proteins in human immunodeficiency virus type 1 (HIV-1) infected individuals. Anal Chim Acta 774:61-6
Feng, Shan; Tian, Enbing; Zhang, Lei et al. (2012) Development of the Fc-III tagged protein expression system for protein purification and detection. PLoS One 7:e44208
Pei, Anna; Li, Hongru; Oberdorf, William E et al. (2012) Diversity of 5S rRNA genes within individual prokaryotic genomes. FEMS Microbiol Lett 335:11-8
Nassry, David D; Phelan, Joan A; Ghookasian, Miganoush et al. (2012) Patient and provider acceptance of oral HIV screening in a dental school setting. J Dent Educ 76:1150-5
Yang, Liying; Francois, Fritz; Pei, Zhiheng (2012) Molecular pathways: pathogenesis and clinical implications of microbiome alteration in esophagitis and Barrett esophagus. Clin Cancer Res 18:2138-44

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