|
Rex Neal Smith
|
Assistant
Pathologist |
|
501 Warren Bldg
|
Cardiovascular, Renal,
Pulmonary, |
|
Department of
Pathology |
Transplantation and Autopsy
Pathology |
|
Massachusetts General
Hospital |
Associate Director, Autopsy
Service |
|
Boston, MA 02421
|
|
|
617-726-1835
|
smith.rex@mgh.harvard.edu |
My research focuses primarily on immunology and
transplantation, with emphasis on the transplantation pathology of the
heart, kidney, and pancreatic islets. I am particularly interested in how
the acute and chronic rejection of allografts and xenograft come about.
Studies involve patients and animal experimentation of heart, kidney, and
pancreatic islet grafts. With expertise in these areas, I am a consultant
pathologist to many investigators within the Harvard community, and to
national consortia with clinical transplant programs. I am also a consultant
to revisions of the classification scheme for human heart allograft
biopsies.
Current emphasis and ongoing work includes cellular and
humoral rejection in cardiac and renal transplantation. I have been able to
correlate indirect immunofluorescence C4d staining with alloantibodies by
retrospective and prospective analysis of the cardiac allograft biopsies.
This study establishes for the first time the correlation between C4d
staining and the presence of alloantibodies. This has been extended to
include immunoperoxidase staining of paraffin sections to study chronic
rejection in cardiac allograft patients with the goal of trying to establish
a link between chronic allograft vasculopathy in human hearts and the
development of alloantibodies.
We are also studying the progression of chronic kidney
allograft rejection that comes about with development of alloantibodies. We
have been able to establish that alloantibodies strongly associate with and
are likely causative of the glomerulopathy of chronic humoral rejection in
allografted kidneys, thereby, establishing that chronic humoral rejection
develops through four stages. Ongoing studies involve the study of allograft
endothelium.
With other investigators we have established that
streptozotocin affects the autoimmunity in NOD mouse (a mouse model of
spontaneous diabetes). We have also established the optimal dose of
streptozotocin for monkey preclinical islets transplant protocols, and have
established that limiting numbers of islets can suffer a non-immunological
senescence. We have established that the failure of an islet allograft was
not immunologically based. With other investigators we are investigating why
the knockout of certain chemokine genes affects graft rejection and ischemic
injury. With investigators at the Transplantation Research Center we have
shown that a complement regulatory protein, DAF, can inhibit acute humoral
rejection to limiting titers of antibody.
With other investigators we are exploring dendritic cell
antigen uptake, optimal protocols for tolerance induction, and
immunomodulatory effects stem cells in mice.
