Cincinnati Children’s Hospital
Medical Center today announced the publication of pioneering research
identifying the crucial role and novel mechanism of action of the protein
RhoH GTPase in the development and activation of cells critical to the
immune system. The findings, along with other studies, suggest that RhoH
GTPase may provide a target for therapeutic intervention in some types of
leukemia. The paper is due to appear in an upcoming edition of the journal
Nature Immunology and was recently posted in the advance online publication
section of the journal’s website, (nature/ni/index.html).
The paper describes detailed genetic and biochemical studies undertaken
by researchers in the Division of Experimental Hematology and the Division
of Immunobiology. The investigators succeeded in identifying a crucial role
for RhoH GTPase in the development of thymocytes and activation of
T-lymphocytes, both key processes in immune cell development. In addition,
the researchers uncovered a novel mechanism for regulating RhoH activity,
which may have broad implications in improving researchers’ understanding
of the mechanism of action of the Rho GTPase protein family and provide a
potential target for leukemia drug development.
“We continue to make important progress in deciphering the molecular
processes involved in the development and maintenance of the immune and
blood system and how disruption of key proteins may contribute to
leukemia,” said David A Williams, M.D., Director of Experimental
Hematology, Cincinnati Children’s. “Through a collaboration with Ohio State
University Comprehensive Cancer Center, we are now focused on translating
these findings into developing new ways to target the protein as a novel
approach to treating hematological malignancy.”
The development of mature white blood cells, including lymphocytes, is
a highly complex process involving cell growth as well as specific genetic
and biochemical steps. Disruption of this process is associated with
diseases such as leukemia.
RhoH GTPase is specific to blood-forming cells. Experiments have shown
that its alteration affects several key steps in the growth and development
of white blood cells. Moreover, clinical samples have implicated RhoH
GTPase as a factor in leukemia and lymphoma. Further work is ongoing to
decipher the specific mechanism of regulation and the function of RhoH
GTPase in the development of white blood cell populations.
About Cincinnati Children’s
Cincinnati Children’s is a 475-bed institution devoted to bringing the
world the joy of healthier kids. Cincinnati Children’s has an international
reputation for clinical and scientific excellence and is nationally the
second largest recipient of research funding from the National Institutes
of Health among pediatric institutions. The Cincinnati Children’s Research
Foundation was founded in 1931 and has a strong heritage of scientific
discovery including advances that have benefited children worldwide such as
the Sabin oral polio vaccine, a rotavirus vaccine and the first practical
heart-lung machine that made open heart surgery possible.
Cincinnati Children’s Hospital Medical Center
Cincinnati Children’s Hospital