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(Atrial Natriuretic Peptide Receptor: Gene expression, structure-function studies, site-specific mutagenesis, gene targeting, molecular basis of hypertension)

Professor
Ph.D.: University of Kentucky
Postdoctoral: Vanderbilt University

The long-term objectives of our research projects are to delineate the molecular and cellular action of atrial natriuretic peptide (ANP) that controls the blood pressure and cardiovascular homeostasis. The regulatory action of ANP is mediated by interacting with guanylyl cyclase/ natriuretic peptide receptor-A (NPRA) that synthesizes the intracellular second messenger cGMP. Interaction of ANP with the NPRA plays a central role in pathophysiology of hypertension and cardiovascular disorders. Our studies are aimed at examining the structure-function relationship of different domains of NPRA cDNA by deletion and site-directed mutagenesis and expression in transfected cells. We hope to learn the structural components that may be involved in ligand-binding, activation of protein kinase-like homology domain, and receptor internalization, trafficking, down-regulation, and desensitization. These studies involve the analysis of the molecular determinants in receptor sequence mediating the overall functioning ability of NPRA, critical for the hormone-dependent signaling process. Our studies are also in progress to examine the transcriptional regulation and function of the murine Npr1 gene (coding for NPRA) using model system cell lines and the Npr1 gene-targeted mutant mice generated by homologous recombination that either disrupted (knockout) or duplicated the Npr1 gene. The impact of Npr1 gene dosage and null mutation will be determined in mutant mice in vivo and in cultured cells isolated from these mice in vitro. These studies should provide the means to test directly the efficacy of NPRA regulatory elements, and the impact of Npr1 gene dosage and null mutation in ANP/cGMP-mediated biological responses.

Recent Publications:

A PubMed listing of research publications for Kailash N. Pandey, Ph.D.

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