Ph.D. Immunology & Molecular Pathogenesis
Emory University, 2002
Cancer Immunology and Human Adenovirus Infection and Leukemia
My laboratory conducts research in the areas of tumor immunology, mechanisms of tumor cell/immune cell interactions, as well as investigating the association of human adenovirus with lymphocytes and leukemia. Ongoing studies involve (1) the analysis of basic anti-tumor immunologic mechanisms and principles, (2) analysis of tumor cell-immune cell interactions and (3) investigating the possibility that human species C adenovirus can initiate acute leukemia.
Radiation-induced enhancement of immunogenicity:
The laboratory performs investigative research in the field of pre-clinical cancer immunotherapy with the goal of impacting the design of better immunologic strategies for the treatment of cancer. One of the major research thrusts in our lab is to continue examining the effects of ionizing radiation on gene expression in human carcinoma tissues to gain further insights into the mechanistic link between irradiation and increased attack by immune cells. Research focuses on those factors that will enhance the activation and activity of human anti-tumor cytotoxic T cells, with emphasis on the effects of sub-lethal doses of ionizing radiation on tumor immunogenicity. Along these lines we are evaluating: 1) the duration of enhanced susceptibility to CTL-mediated lysis, 2) changes in gene-expression of CTL relevant molecules and 3) if this phenomenon is common among solid tumors from diverse tissue types. Additional studies focus on modulation of factors that could activate or regulate other immune cells (including dendritic cells, natural killer cells and regulatory T cells) following exposure of tumor cells to radiation.
Our experimental strategies utilize several techniques in cell and molecular biology including in vitro cell proliferation and apoptotic assays, cytokine production and quantitation, real-time Q-PCR, flow cytometric analysis, immunoblotting techniques, siRNA gene silencing, and in vitro human CTL lytic assays.
Adenovirus infection of lymphocytes and leukemia:
Research is focused on the study of a human tumor viruses that persistently infect lymphocytes. Our previous studies evaluated the molecular characteristics of natural adenovirus infections in human lymphocytes, with emphasis on identifying lymphocyte cell populations in human tonsils and adenoids that harbor the common species C adenovirus DNA. In addition, the molecular dynamics of adenovirus persistence/latency in these naturally infected lymphocytes were examined by evaluating viral DNA replication, transcription, and protein expression. Current research is focused on gaining further insights into the relationship between prenatal adenovirus infection of lymphocytes and childhood leukemia. The goal is to characterize the latent or persistent phase of subgroup C adenovirus life cycle in humans and to reveal wether this virus contributes to some acute leukemia's in children. If research can understand the mechanisms of latency in lymphocytes, this information can be used to target vaccines for the purpose of prevention of acute leukemia in childhood.
The experimental strategies utilize for these studies include a variety of techniques, such as lymphocyte isolation, lymphocyte cell culture, immunohistochemistry, flow cytometry, real time Q-PCR, DNA purification, detection of leukemia associated gene translocations, and virus propagation and purification.