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Genomics Section
James Taylor, MD, Staff Clinician
The research focus of our laboratory group is genetic and genomic approaches to define Mendelian and complex
disease pathogenesis in humans. We have chosen a disease specific approach along with the other research
members of the Vascular Medicine Branch, focusing almost exclusively on sickle cell disease and related
hemolytic anemias. The genomics group’s overall goal is to identify and study the function of genes that
influence susceptibility to high mortality vascular complications of sickle cell disease, like stroke,
pulmonary hypertension, and end stage kidney disease. Specifically, we want to identify genetic variants
or mutations in the genes that will determine whether a person with sickle cell disease will develop
vascular disease during their lifetime. Our objective is to define potential gene targets for novel
therapies for the complications of sickle cell disease, which can be studied as part of clinical drug
trials initiated by the Vascular Medicine Branch. A secondary goal of our research is to develop
resources that will facilitate and encourage the implementation of molecular diagnostic assays in newborn
hemoglobinopathy screening programs and in the clinical practice of hematology.
To accomplish this goal, we collect DNA and clinical/phenotypic information from different groups of sickle
cell patients and healthy controls from around the world for use in gene mapping studies. Much of our time
is also devoted to analysis of gene sequence and expression patterns in order to more efficiently select
priority genes for study in our human gene mapping populations. Finally, we selectively study the functional
consequences of genetic variation in several genes which have been implicated in the pathogenesis of sickle
cell related vascular complications. Members of our genomics group also participate in our Branch's clinical
trials of drugs for sickle cell disease related pulmonary hypertension. Thus, this group’s work is
translational in nature, taking us from a patient's bedside to the genetics lab, and back to the bedside in
an average day.
Our group is focused on clinical investigation in patients with sickle cell disease. This research is
conducted in three major pathways. The first involves measurement of blood flow patterns in the forearm
of patients and healthy volunteers, using a technique called venous occlusion strain gauge plethysmography.
The second involves measurement of blood metabolites in patients with sickle cell disease, at steady state,
during vaso-occlusive crisis, and during forearm blood flow studies, to gather information regarding the
biochemical correlates of sickle cell vasculopathy. We also study blood proteins using proteomic techniques,
particularly high throughput mass spectroscopy, in order to discover new pathways and markers of sickle cell
vasculopathy. This has already been successful in identifying apolipoproteins dysregulated in sickle cell
pulmonary hypertension. Our third pathway involves clinical trial of drugs are promising for improving blood
flow in patients with sickle cell disease.
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