This application address broad challenge area """"""""(03) Biomarker Discovery and Validation"""""""" and specific challenge research topic """"""""03-HL-101* Identify and validate clinically relevant, quantifiable biomarkers of diagnostic and therapeutic responses for blood, vascular, cardiac, and respiratory tract dysfunction."""""""" Treatment paradigms have evolved from studies of patients who, despite similar presentations, may have experienced disparate environmental exposures or clinical courses and may have varied underlying pathobiologies. A developing and exciting biomarker strategy is the measurement of microparticles (MPs) and assessment of circulating progenitor and mature endothelial cells. All eukaryotic cells shed MPs in response to activation or apoptosis and elevation of plasma MPs, particularly those of endothelial origin, reflects cellular injury and is a surrogate marker for vascular dysfunction. Microparticles have been enumerated in a number of conditions where vascular dysfunction and inflammation are important pathophysiological mechanisms, for example coronary artery disease or thrombotic microangiopathies. We recently completed a pilot study evaluating levels of MPs in patients with diabetes mellitus (DM) and compared flow cytometry results with those of a non cell specific Enzyme Linked ImmunoSorbent assay (ELISA). The ELISA assay results correlated with flow cytometry results but did not distinguish the cell of origin where the micoparticle originated. The overall goal of this study is to develop and validate a novel cell-based high throughput, high content, vascular health profile analysis that provides a signature for individuals at high risk for cardiovascular events. A unique biocomputational approach at Penn called cytometric fingerprinting will be used to identify populations of cells.
The aims are: 1: To develop and validate a single platform high throughput, multiplexed flow cytometry assay for cell specific MPs, endothelial progenitor cells and hematopoietic progenitors. 2: To develop and validate a cell specific ELISA biomarker assay for MPs in healthy group of subjects and patients with DM and correlate with an independent flow cytometry test for EPCs and HSCs as a dual platform measure of vascular health. 3: To use high order informatics to derive a signature profile from the results of Aims 1 and 2. Such a high throughput high information content approach may prove to be clinically useful in discerning laboratory markers that would be useful for guiding therapy of patients with DM. Penn Medicine contributes substantially to the local economy. In 2008, Penn Medicine created 37,000 jobs and $5.4 billion in regional economic activity, with the area's highly trained workforce producing more than 24,600 applications for just 840 open Penn staff research positions. The current proposal will create or retain 3 jobs. If successfully validated, the biomarker technology proposed could be commercialized, create thousands of jobs in the health care industry and potentially prevent costly hospital admissions. Also, an ELISA for MPs could provide an early evaluation of impact of novel pharmaceutical compounds on vascular health. If successfully validated, the biomarker technology proposed could be commercialized, create thousands of jobs in the health care industry and potentially prevent costly hospital admissions. Also, an ELISA for MPs could provide an early evaluation of impact of novel pharmaceutical compounds on vascular health.
If successfully validated, the biomarker technology proposed could be commercialized, create thousands of jobs in the health care industry and potentially prevent costly hospital admissions. Also, an ELISA for MPs could provide an early evaluation of impact of novel pharmaceutical compounds on vascular health.
| Rogers, Wade T; Zhang, Lifeng; Welden, Scott et al. (2017) Vascular Health Profile predicts cardiovascular outcomes in patients with diabetes. Cytometry B Clin Cytom 92:258-265 |
| Englund, Erin K; Rodgers, Zachary B; Langham, Michael C et al. (2016) Measurement of skeletal muscle perfusion dynamics with pseudo-continuous arterial spin labeling (pCASL): Assessment of relative labeling efficiency at rest and during hyperemia, and comparison to pulsed arterial spin labeling (PASL). J Magn Reson Imaging 44:929-39 |
| Kurtzman, Nicholas; Zhang, Lifeng; French, Benjamin et al. (2013) Personalized cytomic assessment of vascular health: Evaluation of the vascular health profile in diabetes mellitus. Cytometry B Clin Cytom 84:255-66 |
| Curtis, Anne M; Edelberg, Jay; Jonas, Rebecca et al. (2013) Endothelial microparticles: sophisticated vesicles modulating vascular function. Vasc Med 18:204-14 |
