The Vascular Biology of Critical Illness laboratory of Robert L. Danner, MD at the Critical Care Medicine Department at the National Institutes of Health Clinical Center and NHLBI is seeking a postdoctoral fellow to evaluate endothelial dysfunction and therapeutic targets in acute and chronic conditions such as COVID-19, septic shock, and pulmonary arterial hypertension (PAH). Despite marked differences in the tempo of disease progression and hemodynamic consequences for affected vascular beds, these conditions share vascular dysfunction, end-organ injury, and the potential for lethality. Our lab studies the mediators, signal transduction pathways, and underlying mechanisms of endothelial dysfunction and injury with the goal of developing therapeutic strategies that specifically target vascular inflammation and dysregulated signal transduction.

Endothelial injury underlies the development of multiorgan failure in acute COVID-19 and an increased risk of late cardiovascular complications including stroke and myocardial infarction. Notably, this extended period of endothelial dysfunction is poorly understood, and diagnostic and therapeutic approaches are entirely lacking. Cell-cell and cell-virus interactions occurring in the COVID-19-afflicted vasculature are being evaluated with a particular focus on endothelial senescence. The lab has access to deeply phenotyped patient cohorts, a bioengineered three-dimensional disease-on-chip in vitro system, and a b-coronavirus mouse model that closely recapitulates key aspects of human disease.

Pulmonary arterial hypertension is characterized by pathologic pulmonary vascular remodeling with vascular cross-sectional loss leading to right ventricular failure and death. Endothelial cells with molecular defects in PAH-associated genes such as BMPR2 and CAV1 are being used to develop a complete picture of pathogenic mechanisms and therapeutic targets. Approaches targeting these mechanisms at points of convergence have the potential to arrest or even reverse pathologic vascular remodeling in PAH. Our lab has standard molecular biology equipment, flow cytometry, a cell sorter, high-throughput expression profiling and proteomic platforms, and a state of-the-art incubator system. The SU-5416/hypoxia rat model of PAH is available for the preclinical testing of therapeutic approaches arising from basic science discoveries. An active clinical research program in PAH within the department provides access to patient samples and a pathway to clinical trials. Resources are enhanced by collaborator and industry partners.

Applicants must have the following: Ph.D. degree in the Biological Sciences, conferred within the last five years, with an interest in translational research related to vascular biology and signal transduction. Qualified candidates should have direct experience with many of the following laboratory techniques: Cell culture including primary cells, stem cell differentiation, phenotypic and functional assays (e.g. proliferation, apoptosis, reporter genes), cell transfection, ELISA, western blotting, RNA purification, qRT-PCR, CRISPR, and site directed mutagenesis. Expertise in confocal microscopy, flow cytometry, and microfluidics would be highly valued. The candidate is expected to conduct semi-independent research and function as part of a team. A strong background in cell signaling and molecular biology is required. Previous experience in vascular biology is highly desirable.

Please send a cover letter, a CV including bibliography, and the names and contact information for three references to Gabriela Ferreyra, PhD, Laboratory Manager (gferreyra@cc.nih.gov ).

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