Department of Infectious Diseases and Microbiology (IDM) faculty members have been awarded more than $150 million in funding from the National Institutes of Health (NIH) and other agencies over the past 10 years. Since 2003, Pitt Public Health has consistently ranked third nationally in NIH funding among comparable institutions. Our research involves students, postdoctoral fellows, and highly trained support staff.
The following are examples of standout funded IDM faculty research.
HIV and Development of HIV Vaccines and Immunotherapies
Pitt Public Health has received a five-year, $7.2 million grant from the National Institute of Allergy and Infectious Diseases to develop microbicides against HIV transmission. Microbicides are substances designed to prevent or reduce the sexual transmission of HIV when applied topically to the vagina or rectum. The grant will allow researchers to test two formulations—a film and ring—that release the active ingredient over time. They will likely have to test many products before finding one that is safe and effective against HIV as well as easy to use and acceptable to both sexual partners. “The HIV/AIDS epidemic remains uncontrolled in many regions in the world,” said principal investigator Phalguni Gupta, Professor and Assistant IDM Chair. “In developing countries, HIV is most often spread through unprotected heterosexual intercourse, creating a great need for new ways to prevent transmission beyond the condom whose use is often at the discretion of men.” They also plan to test the microbicides in the presence of other sexually transmitted diseases and bacterial vaginosis, a common vaginal infection.
Complications of Antiretroviral Therapy
Assistant Professor Jeremy Martinson is leading research on genetic factors affecting cardiovascular complications of HIV therapy. The introduction of Highly Active Antiretroviral Therapy (HAART) has transformed the lives of many HIV-positive individuals. For some, however, HAART carries a risk of cardiovascular side effects, although the etiology of this is unknown. HIV infection is known to contribute to cardiovascular disease risk in some patients. Martinson and his team are investigating the extent to which host genetics, HIV infection, and treatment with HAART interact to give rise to cardiovascular disease in patients enrolled in the Multicenter AIDS Cohort Study. They are currently using a variety of high-throughput genomic and transcriptomic approaches to study this phenomenon.
AIDS Education and Prevention
“Disparities in health care, the stigma of HIV/AIDS, and the need for more timely testing and treatment are still barriers to delivering and improving HIV care,” said Linda Frank, Associate Professor. Frank is a principal investigator at the Pennsylvania/MidAtlantic AIDS Education and Training Center, headquartered at Pitt Public Health since 1988. The center is a national leader in supporting the training and education of health professionals who care for the thousands of people infected annually with HIV in the United States. A recent grant will allow scientists like Frank to continue to provide critical training to health professionals to reduce barriers to HIV care, increase HIV testing, integrate HIV prevention into primary care, and improve linkages to HIV treatment and expert clinical management of HIV and other comorbid conditions, such as hepatitis, sexually transmitted infections, tuberculosis, and substance use.
Recent studies in the laboratory of Assistant Professor Giovanna Rappocciolo, have identified DC-SIGN and langerin, two C-type lectins, as the main receptor used by human herpesvirus 8 (HHV-8), or KSHV, the cause of Kaposi's sarcoma, to infect dendritic cells, dermal dendritic cells, B lymphocytes andmacrophages. These findings established the first in vitro model of productive HHV8 infection of its natural target cells.
Recent studies in the laboratory of Assistant Professor, Giovanna Rappocciolo have identified dysregulation of cholesterol metabolism pathways in antigen presenting cells as regulator of HIV-1 disease progression in the absence of antiretroviral therapies. Recent studies are now identifying signaling metabolites and specific miRNAs as modulators of cholesterol metabolic pathways in individuals naturally able to control HIV-1 disease progression.
Nearly one third of the world’s population is infected with Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). Although the vast majority of M. tuberculosis-infected people never experience the clinical symptoms of TB, there are almost 11 million new cases of TB and two million TB-related deaths annually. HIV is strongly associated with active TB, even in individuals with well-preserved CD4+ T cell levels, and TB is the leading cause of death in HIV-infected individuals. The causes of active TB are poorly understood, but are likely to include changes in anti-mycobacterial immune responses in granulomas, the site of M. tuberculosis infection. Assistant Professor, Josh Mattila and his lab are focused on understanding the immune environment in lungs and TB granulomas. His particular interest is examining interactions between myeloid cells, including macrophages and neutrophils, and T cells in this environment with the objective of identifying factors that differentiate pathologic and protective responses.
T cells (red) and macrophages (green) are present in distinct regions in granulomas where they cooperate to control Mycobacterium tuberculosis infection.
Influenza virus is a respiratory pathogen that targets the lung, and innate immune responses serve a key role in providing early antiviral immunity and limiting disease in acute infection. However, the relationship between dendritic cells and immunity in the lung is not well defined. Professor Simon M. Barratt-Boyes and his team have used the murine model to examine the impact of plasmacytoid dendritic cells in the early immune response to influenza virus infection. They are also studying the dynamics of the dendritic cell response to avian influenza virus infection in the lung of nonhuman primates, which they believe serves as a more robust model of influenza in humans than do mice.
HIV-1 Associated Neuropathogenesis and Biomarker Discovery
HIV-associated neurocognitive impairment (HAND) is commonly observed in AIDS patients worldwide. During early infection, HIV-1 enters the Central Nervous System (CNS) and resides in macrophages/microglia and causes neuronal degeneration and inflammation in the brain. HAART therapy has improved the quality of life and longevity of HIV-1 infected patients; however, with aging, the prevalence of HAND is high in this population. Velpandi Ayyavoo’s laboratory focuses on understanding how HIV-1 induces neuronal dysfunction and destruction and how to detect them during the early stages as neurodegeneration occurs over a long period of time resulting in clinical manifestations. Her team uses several genomic and proteomic approaches to develop early biomarkers to detect HAND. Additionally, results from this study will help to identify novel targets and to design new therapeutics against HIV-1 in the central nervous system.