Profile
The focus of my research is to study the role of the adaptive
immune system in disease pathogenesis and to clearly define the
mechanisms that regulate pathogenesis. By dissecting the host-cell
interactions in granulomatous inflammation, I hope to identify host
factors that may be exploited for novel therapies in chronic lung
disease. Moreover, by investigating the role of individual cell
subsets in granulomatous formation and maintenance, I hope to gain
insight into how granulomatous inflammation is initiated and
progresses to chronicity. Currently, I use sarcoidosis as a model
system for granulomatous inflammation. Sarcoidosis is a unique
disease which is at the crossroads of microbial infection and host
immune response. Specifically, sarcoidosis is a multisystem
granulomatous disease of unknown etiology, characterized by a T
helper 1 (Th1) immunophenotype. Although sarcoidosis is a systemic
disease, it most commonly affects the lungs. The immune response in
sarcoidosis has been well characterized, however the lack of
antigen has hindered in-depth analyses of the role of specific
cells in sarcoidosis pathogenesis. Recent reports from independent
laboratories have postulated mycobacteria as a candidate. The
potential role of mycobacteria in sarcoidosis immunopathogenesis
has been demonstrated by the detection of mycobacterial proteins
and nucleic acids in sarcoidosis granulomas, as well as humoral and
peripheral cellular immune responses to mycobacterial antigens in
sarcoidosis subjects. In addition, our lab has made significant
advances in studying the immune response to mycobacterial antigens
at the site of active sarcoidosis involvement – the lungs. Our
lab has demonstrated the presence of antigen-specific recognition
of mycobacterial proteins in CD4+ and CD8+ T cells derived from
sarcoidosis subjects at diagnostic bronchoscopy. The current focus
is to delineate CD8+ molecular and biologic T cell function in
sarcoidosis pathogenesis and how it influences sarcoidosis
resolution or progression. In addition, we are interested in how
HLA types correlate with disease outcome.