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Rakesh Sindhi, MD, has
been awarded a $1.1 million
grant from the National
Institutes of Health.
PITTSBURGH – Oct. 11, 2006 –
A Children’s Hospital of
Pittsburgh of UPMC
transplant surgeon and
researcher has received a
grant from the National
Institutes of Health to
study genetic factors that
could predispose transplant
recipients to rejection.
The goal of the four-year,
$1.1 million grant is to
study these factors in order
to predict – before
transplant – which patients
are more likely to
experience rejection. This
information may be used to
tailor anti-rejection
medications accordingly,
according to Rakesh Sindhi,
MD, co-director of
Children’s Hillman Center
for Pediatric
Transplantation and
principal investigator of
the study. He plans to
enroll 80 children receiving
liver transplants at
Children’s.
“Based on the results of
this study, a patient more
likely to reject a
transplanted organ may
someday receive high doses
of anti-rejection medicine
initially. Those who are
less likely to reject could
have lower doses, or less
potent combinations,” said
Dr. Sindhi, an associate
professor of surgery at the
University of Pittsburgh
School of Medicine. “By
applying individualized
anti-rejection strategies
before the transplant even
occurs, we hope to reduce
rejection rates and
drug-induced side effects
for pediatric liver
transplant from 50 percent
to about 20 percent.”
Surgical techniques have
improved survival rates for
pediatric organ
transplantation dramatically
over the last 25 years. As a
result, the challenge has
shifted to improving quality
of life. Anti-rejection
medications are important
because, while they make
transplantation possible,
they also can have adverse
side effects that can
themselves become
life-threatening, such as
infections and cancers.
Researchers will study the
multiple processes that
cause rejection in blood
cells. This information will
be linked to the unique
“genomic fingerprint” of a
liver transplant candidate,
based on the inheritance of
more than 500,000 mutations
from parent to child. These
mutations, known as
nucleotide polymorphisms,
represent “misspellings” in
the genetic code, are
present in all people and
form the basis of inherited
predisposition to a variety
of diseases and outcomes,
according to Dr. Sindhi.
“There is evidence from our
earlier research that these
mutations can be transmitted
from parent to child in
certain patterns that
indicate if a transplant
candidate is predisposed to
rejection, a rejection-free
state or tolerance, a rare
occurrence whereby
anti-rejection medications
no longer are required,” he
said. “Any tool that could
help guide us in deciding
when and by how much to
lower anti-rejection
medications would be
invaluable in improving the
quality of life for our
patients.”
Dr. Sindhi’s grant is from
the National Institute of
Allergy and Infectious
Diseases. Grant
collaborators include: the
Genetics and Proteomics
Laboratories at Pitt; the
Department of Human Genetics
at Pitt; Duke University;
and the EMMES Corporation in
Bethesda, MD.
For more information about
Dr. Sindhi’s research or the
Hillman Center for Pediatric
Transplantation at
Children’s, please visit
www.chp.edu.
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