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Functional Genomics for studying rejection in Heart
Transplantation
Heart transplantation is the definitive
therapy for end-stage heart failure but is complicated by recipient immune
responses to the allograft, often resulting in cardiac allograft rejection.
Upon presentation of allo-antigen by donor- or
recipient antigen-presenting cells, recipient T-lymphocytes develop to
T-helper cells (CD4+ T-cells) and cytotoxic
T-cells (CD8 T-cells) and B-lymphocytes develop to plasma cells producing
specific clones of antibodies. These immunocompetent
cells destroy the foreign cells. In addition, an inflammatory response
involving monocytes and macrophages participates
in this alloimmune response. The differentiation
of this alloimmune response is orchestrated by a
subtle regulation of soluble immune mediators, called cytokines.
Different forms of rejection are being
recognized, acute cellular (or T-cell-mediated) rejection, acute
antibody-mediated (or B-cell-mediated) rejection, mixed rejection and
chronic rejection, also termed transplant vasculopathy.
We are currently exploring the data
generated from the CARGO study to better understand this
three conditions in collaboration with the Columbia Genome
Center using
conventional immunology techniques and microarray
technology within a systems biology theoretical framework.
Ongoing projects:
Molecular mechanisms of rejection
Gene
expression profiles of Antibody-mediated rejection
Gene
expression profiles of Chronic Rejection (Transplant Vasculopathy)
Reconstruction of regulatory cellular networks during rejection
and quiescence
Brief
Overview of Methods used in Genomic and Systems Biology Research
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