When patients receive an organ transplant they must take immunosuppressive medications for life to prevent rejection. These drugs are incompletely effective and cause significant morbidity. My research is directed toward understanding transplant rejection and translating this understanding into…
more less morbid therapies for transplant recipients. My group uses in vitro and animal models to develop transplant strategies and then investigates them in clinical trials. We have successfully targeted several costimulatory molecules with monoclonal antibodies in primates and are evaluating multiple anti-CD154 approaches pre-clinically. We are interested in the expression of CD154 on platelets and its implications for immune activation and thrombosis. We have initiated several clinical trials using monoclonal or polyclonal antibodies to achieve transient lymphocyte depletion substantially reducing the need for immunosuppression in humans. We have shown that monocytes play a key role in post-depletional immune responses and are evaluating the signals influencing human monocytes during lymphopenia. We have also determined that memory T-cells are disproportionately spared during depletion in humans and are studying how this affects the post-transplant need for immunosuppression. We are also developing more precise methods for monitoring transplant recipients and hope that more precise monitoring techniques will facilitate tailor-make immune therapies with improved patient outcomes.
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