My main area of research is immune regulation, with two main focuses: 1) chronic immune system activation and 2) the ontogeny of the human immune system.
In the case of chronic activation, the delicate balance between immune effector responses and counter-activation is perturbed. My colleagues and I are pursuing studies of one of the principal mechanisms that modulate this balance, which is a subset of CD4+ T cells called regulatory T cells. We study the biology and function of these cells in the setting of acute and chronic immune activation (HIV infection, aging and fetal inflammation). In particular, my team and I were one of the first to show that the frequency of regulatory T cells increases during chronic HIV infection or aging, which prevents many aspects of harmful, unregulated inflammation. However, it acts as a double-edge sword, blunting other immune responses to other pathogens or vaccines.
The second major problem we study is the ontogeny of the human immune system, and how it reacts to infection and inflammation. Recent findings from my laboratory and others have shown that the human fetal immune system is not inactive, and it starts reacting early on to inflammation and pathogens, but differently when compared to the adult version. This knowledge is the basis of the novel theory of the “fetal origins of diseases,” e.g., early exposure to antigens and inflammation, and the responses it elicits, may shape long-term responsiveness. However, many aspects are still unknown due to the difficulty in obtaining samples in humans. We mainly use non-human primate models to address these questions.
Most of my work is conducted in multi-disciplinary teams. This collaboration is especially necessary when working with human subjects or large animal models, such as non-human primates. The constant interactions with different colleagues, clinicians, statisticians, bio-informaticians and other basic scientists are among the most stimulating and remarkable aspects of my job.
I first joined the team at the Cincinnati Children’s Hospital Medical Center in 2001. My research has been published in numerous journals ,including JCI Insights, Blood, Frontiers in Immunology, PLoS ONE, Journal of immunology and The Journal of Pediatrics.
Professor, UC Department of Pediatrics
Molecular Immunology, Immunobiology