Project Details
Description
This proposal includes: one clinical Project l_Proje-t 2: PI: Dr. Fabry) that builds on the pioneering work of the Pi in the .:
la cycle on the development of BOLD-MRI and now near infrared spectroscopy (NIRS) to measure oxygenation:.
pension and blood volume it, sickle cell patients and novel sickle transgenic mice. The objective is to determine if these
state-of-the-art technologies can help in the evaluation ofsicMe damage to brain, kidney and muscle. In addition, there
are three Translationa! Research projects, that aim at finding potentially helpful therapeutic interventions in SCD by the
pre-clinical development of several basic research strategies. They are: Project I (PI: Dr. Acharya) who is interested in
generating a globin chain that has more polymerization inhibitory potential than the paradigmane HbF, based on the
pioneering f'mding, in the previous cycle, that pig-sigma-chain completely neurralizes human B5-polymerization.The follow-up
to define the minimum number of pig-gamma-chain sequences that are sufficient to confer the desired properties on the human
Gamma globin chain. In the process, we will learn about the quinary structure of sickle polymer as well as the refinement of
semisynthesis. Project 3 (PI: Dr. Kaul), also builds on work done in the previous cycle, but the present proposal aims
at a quantum leap of knowledge as it pertains to: testing the hypotheses that a heterogenous array of red cell integrins and
vWF, P-selectin, laminin, and NO are involved in sickle adhesion, and testing the hypothesis that gamma, beta3, anionic
polysacharides, and hydroxyur, can be useful in blocking sickle cell adhesion. Project 4 (PI; Dr. Nagel), builds on a
long interest in ti,.emulfigene involvement in the sickle phenotype. This project aims at defining, by state-of-the art
microarray technology, the genes responsible for the pleiotropic effects in sickle cell anemia, as well as which of these
have epistatic (modifier) capability to define severity risk and to explore potential epigenetic effects in B-gene cluster
haplotypes linked to the sickle gene. The projects are supported by an Administrative Core, Transgecnic Core (in the
forefront of developing sickle animal models), by a micro-CHIP Core (supposed also by our in-house Microarray
Facility), a strong Clinical and Patient Services Core, that have pioneered the Day Hospital concept into reality, with the
purpose of treating sickle cell anemia patients with uncomplicated painful crises in a way that greatly improves their rate
of recovery, their hospitalization rates that also favorably affects the in house hospitalization length of stay. This proposal
is complemented by two above-the caplemented by two above -the-cap Clinical Project Proposals, both based on last cycle accomplishments.
Status | Finished |
---|---|
Effective start/end date | 7/1/03 → 3/31/08 |
Funding
- National Heart, Lung, and Blood Institute: $7,322,833.00
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