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A phosphopeptide multiplex PRM mass spectroscopic biomarker assay for PAH
Phone: (347) 453-8547
Email: rs@pulmokine.net
Phone: (518) 573-8315
Email: lz@pulmokine.net
The purpose of this phase SBIR grant is to develop a quantitative phosphopeptide biomarker assay for
pulmonary arterial hypertension PAH The commercial product will consist of a kit of stable isotopically
labeled internal standards of a selected set of phosphopeptides either up or down regulated in PAH The set of
stable isotopically labeled peptides will be used in a parallel reaction monitoring PRM mass spectroscopy
MS assay to quantify the level of target phosphoproteins in the buffy coat fraction of blood
We propose to determine if a subset of these phosphoproteins are differentially regulated in peripheral blood
mononuclear cells PBMCs buffy coat which contains lymphocytes and platelets of subjects with PAH
compared to controls to develop assays that can be used to determine how the levels of these
phosphoproteins change over time and to determine if these levels correlate with clinically important
endpoints i e mortality risk hospitalization for PAH and listing for lung transplant
We propose that a set of increased and decreased phosphoproteins in PBMCs will identify a subset of patients
with a poor prognosis who are less likely to respond to currently approved therapies and allow earlier
interventions to modify the course of their disease and improve their outcomes
The chosen targets are based on a phosphoproteomic analysis of iPAH lung tissue compared to controls that
Pulmokine performed in collaboration with the Rensselaer Center for Translational Research and the Yale
University Proteomics core Several dramatically increased and decreased phosphoproteins implicated in
immune regulation cell proliferation and angiogenesis were identified
This feasibility study will develop a PRM MS assay that can simultaneously quantify the phosphoproteins
implicated in immune regulation cell proliferation and angiogenesis previously identified as highly regulated in
iPAH and which will include several novel targets The assay will be tested on buffy coat cell extracts from blood
samples of iPAH and systemic sclerosis associated PAH SSC APAH with comparison to SSC without PH and
to normal controls These samples will be obtained prospectively by Dr Todd Bull the director of the University
of Colorado PH program
Phase of the project will address regulatory requirements for kit commercialization provide a longer validation
study and perform serial sampling of subjects with iPAH to correlate biomarker results with clinical course and
prognosis Pulmonary arterial hypertension is a devastating disease with a high morbidity and mortality
This project is relevant to public health because it could ultimately lead to improved diagnosis
and better therapeutic management of patients with pulmonary arterial hypertension
* Information listed above is at the time of submission. *