Immunobiology of Aging.  Aging has two faces. One face pertains to age-related physiologic damage; hence we are investigating the immunology of frailty, a discrete clinical syndrome in which affected elders (defined as 65 years and older) are functionally dependent on others for their activities of daily living. The other, less studied face of aging is successful aging, exemplified by community dwelling elders who are highly functional despite long history of diseases and/or concurrent co-morbid conditions. We are interested in the fundamental question: What are the immunologic determinants of long-term survivorship? Seeking answer(s) to this question requires a research paradigm shift from the usual young-vs-old comparisons to cursory evaluation of clinically-defined groups of elders. To complement these human studies, we also are examining a mouse model of successful aging, the PAPPA^-/- mouse, a novel strain that has 40% extension in lifespan, has low levels of midlife/late life pathology, and is resistant to age-associated thymic atrophy. 

Immunobiology of inflammatory syndromes. We focus on juvenile idiopathic arthritis (JIA) and adult-onset rheumatoid arthritis (RA). We are pursuing the role of premature immune aging as an etiology of these rheumatic diseases. This is based on our findings about telomere erosion and in vivo accumulation of senescent or pre-senescent T cells disproportionate with age. Hence, we are of the opinion that RA and JIA are suitable models of immune aging. We interested in three questions: What drives immune cell senescence in JIA and RA?  Are prematurely senescent immune cells the cause of disease, and be targets for therapy?