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AIDS-Associated Opportunistic Infections and Cancer

CFAR SOIC SWG members

AOIC SWG leadership

Micah Luftig, Ph.D., (SWG leader)
Bryan Cullen, Ph.D. (oversight)

AOIC SWG activities

AOIC SWG Quarterly Lunches:

Our group meets quarterly over lunch to discuss research progress and opportunities for collaboration and new funding.

AOIC SWG Pilot Grant Program:

In the Spring of 2014, we initiated our AOIC pilot grant program to support new collaborations and research projects in AOIC-related research. We are pleased to announce our first awardees: Drs. Joel Boggan and Dave Walmer for their studies entitled  “Evaluating the accuracy of portable colposcopy and determining the most prevalent HPV genotypes among HIV positive women in Haiti”

We plan to solicit applications in FY15-16 for our second round of funding.

Highest priority opportunities of the AOIC SWG

High Priority Opportunity #1: We will focus on studies of HIV-associated co-infections and cancer in international settings.

We will capitalize on several strengths at Duke that already provide support and infrastructure for international studies in HIV-associated research. The DGHI as well as the Global Cancer Program within the DCI oversee much of these important projects. For many years, Duke and the CFAR have maintained a vibrant collaboration with the Kilimanjaro Christian Medical College including support for clinical fellows and research staff. Recently, this site was awarded a D43 grant from the Fogarty International Center to support training in cancer care and research, which complements existing strengths in HIV immunology, treatment, and community outreach. Additional support for AIDS malignancy research has come to Duke through a CFAR administrative supplement, which has supported several DGHI-affiliated pilot studies in Haiti, Tanzania, and Kenya. In the future, we anticipate supporting collaborative research efforts in HIV-related global health activities through the Developmental Core with our annual RFP program. Indeed, our first RFP recipient will study HPV genotypic variants in HIV-infected women in Haiti (Boggan and Walmer, co-PIs).

High Priority Opportunity #2: We will focus on genetic and genomic changes associated with increased risk of infection or cancer in the setting of HIV. These studies include those analyzing genetic susceptibility of the host, genetic variation of pathogens, and somatic variants in malignant tissue in the setting of HIV.

Several ongoing projects across the AOIC SWG focus on understanding the role of human variation in susceptibility to infection and in understanding somatic variants important for driving lymphomas and other cancers. For example, David Tobin’s lab uses a combination of zebrafish genetic screens and analysis of human genotyping data to understand mechanisms underlying differential susceptibility to tuberculosis infection and treatment outcomes. This work is currently being extended to HIV-infected cohorts in Central America.

In addition, genomic studies of pathogen variants in HIV-infected versus negative individuals are illuminating mechanisms of pathogenesis and identifying novel therapeutic approaches. Within the AOIC SWG, this includes studies of MDR/XDR TB (SH Lee and Frothingham), Cryptococcus neoformans (Perfect and Heitman), and HPV genotypes (Walmer). Furthermore, the analysis of somatic variants in HIV-associated lymphomas relative to sporadic tumors (e.g. Burkitt’s and Diffuse Large B-Cell Lymphomas) is being studied to discern the role of HIV in lymphomagenesis (Dave and Luftig).

High Priority Opportunity #3: we will focus on the specific nature of immune dysfunction that promotes susceptibility to co-infection and cancer in HIV-infected individuals.

The alterations in lymphocyte function during HIV infection, even in the presence of ART, have profound consequences on the susceptibility to infection and cancer. Despite our knowledge that HIV targets CD4+ T cells critical for promoting memory and effector functions in controlling infection; our understanding of the precise immune cell specificities that contribute to the prevention of co-infection and cancer are quite limited. Thus, a high priority for the AOIC SWG will be to capitalize on the strengths of the CFAR Immunology Core and investigators that study immune dysfunction in the setting of HIV (Ferrari, Murdoch, Yang) towards identifying critical immune cell subsets important for controlling co-infection and cancer. We anticipate supporting studies that bring individuals focusing on specific pathogens and immunologists together to address these critical questions. An example of this interaction includes a new collaboration initiated out of an AOIC SWG quarterly lunch meeting to study the role of NK cells in controlling HCV in HCV/HIV co-infected individuals (Naggie, Ferrari).

Specific Aims for the AOIC SWG

Specific Aim 1. Foster intra-CFAR and cross-institutional collaborations in AOIC-focused research. We will promote interaction and collaboration to support AOIC research at Duke by focusing on: i) communication of new funding opportunities and meetings, ii) hosting regular AOIC-related scientific gatherings, and iii) sponsoring mini-symposia and seminars.

Specific Aim 2. Develop new, high-impact scientific research programs in AOIC. The second major goal of the AOIC SWG is to develop new collaborations into robust, high-impact research programs. While our activities in Aim 1 will enable collaborations to blossom, we will also offer an annual pilot program funding innovative proposals in AOIC research.