Dr. Daniel Malamud, a Professor of Basic Science & Craniofacial Biology at NYUCD, has been awarded a five-year, $6.2 million grant from the National Institute of Dental & Craniofacial Research (NIDCR) of the National Institutes of Health (NIH) to head up a research collective consisting of four inter-related research projects, along with Administrative/Biostatistical and Clinical Core components. The collective’s overall goal is to define the interactions between host defense molecules and bacteria in HIV infection and subsequent antiretroviral therapy.
The collective consists of teams from NYUCD, New York University School of Medicine (NYUSOM), and the Aaron Diamond AIDS Research Center (ADARC). Dr. Malamud has assembled a talented group of investigators-all located within a few blocks of each other on First Avenue in New York City.
The study is an intriguing one, notes Dr. Malamud. We are going to recruit a population of people who are HIV-infected but are drug naïve, so they haven’t even been put on treatment yet. New York City is probably one of the few places in the country where the study could be done.
The entire proposal utilizes the same case-controlled study population consisting of 85 HIV+, HARRT-highly aggressive antiretroviral therapy-naïve subjects who will subsequently begin antiretroviral therapy. There will also be a similar cohort of HIV– subjects. The clinical core will obtain oral and GI samples, monitor patient progress, carry out complete oral health examinations, and maintain all subject records.
We’re going to take a variety of samples from the subjects, and then we are going to put the HIV+ subjects on drug treatment for two to three years, said Dr. Malamud. We want to see how various parameters throughout the GI tract are affected by HIV infection and then by the subsequent control of HIV through a cocktail of drugs, known as HARRT.
The first of the research collective’s four projects, Project 1, headed by Dr. Linqi Zhang, of the ADARC, will determine the whole saliva proteome comparing HIV–, HIV+/HAART naïve, and HIV+ post-HAART samples. Dr. Zhang’s studies will focus on soluble molecules that are part of the innate host defense system.
Dr. Malamud is a well-recognized HIV expert in the dental science field,said Dr. Zhang. When I learned that Dr. Malamud was coming to NYU, I had the opportunity to show him my lab at ADARC where we have been very interested in HIV infection in mucosal settings, in particular the oral cavity and the GI tract. With this study, we will be able to compare bacterial and viral factors in these two distinct environments-in the same host-so we can better understand the disease and help to design better anti-HIV drugs and vaccines.
Project 2, headed by Dr Yihong Li, Associate Professor of Basic Science & Craniofacial Biology at NYUCD, will define the oral microbiota in HIV– vs. HIV+ saliva samples, and HIV+ before and after HAART. Dr. Li’s 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.
We will collect samples from multiple sites from the same individual, said Dr. Li, which will enable us simultaneously to compare the bacteriological composition, in order to make inferences about shifts in the ecological balance of the microbial community. To date, no such study has been done or reported in the literature.
Project 3, headed by Dr. Michael Poles, NYUSOM, will study the remainder of the GI tract using endoscopy to obtain fluid and biopsy samples. Dr. Poles’s study will focus on innate immune mediators and GI microbes, and his data compared to the findings of Projects 1 and 2.
This collaboration dovetails beautifully with my research interests, said Dr. Poles. I am most excited to be working with such an amazing PI as Dr. Malamud and the amazing cadre of investigators he has assembled. I expect that this project will yield an enormous amount of vital information about HIV pathogenesis and mucosal immunology.
Project 4, headed by Dr. Malamud, will study antibacterial and antiviral activities in saliva, focusing on the innate host defense system. In addition, Dr. Malamud will determine the ability to infect buccal vs. rectal tissue in vitro, and compare the HIV-1 variants obtained from oral, GI, and blood. The Administrative/Biostatistical Core, led by Dr. Malamud and Dr. Robert Norman, Research Associate Professor of Epidemiology & Health Promotion, 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.