Graduated in 2000 from Department of Biological Sciences at University of Buenos Aires (Argentina)

Postdoctoral studies (2000-2007), Dept. of Medicine, University of Mississippi Medical Center

Postdoctoral studies (2007-2008), Dept. of Physiology and Biophysics, University of Mississippi Medical Center

Assistant Professor (2008-present), Dept. of Biochemistry, University of Mississippi Medical Center

RESEARCH INTERESTS

CURRENT PROJECTS

RGS proteins and their role in adrenal aldosterone secretion and aldosterone-mediated hypertension and target organ injury

Angiotensin II binds to its receptor in adrenal cells and through activation of G-proteins transduces and amplifies its intracellular signaling to increase aldosterone secretion. Angiotensin II signaling is inefficiently terminated by the G-proteins endogenous GTPase activity. Regulators of G-protein Signaling (RGS) proteins increase G-proteins GTPase activity thousands of times thus accelerating Angiotensin II signaling termination. We have reported that RGS2 and RGS4 are expressed in adrenocortical cells, their expression is upregulated by Angiotensin II and RGS2 or RGS4 overexpression decrease Angiotensin II-mediated aldosterone secretion in vitro, suggesting that RGS2 and RGS4 proteins are a “turn off” mechanism of Angiotensin II-mediated aldosterone secretion in adrenal cells. Currently we are studying adrenal RGS proteins regulation in vivo under physiological and pathophysiological conditions. We are also analyzing RGS proteins role in aldosterone secretion, and aldosterone mediated hypertension and target organ injury.

Aldosterone regulation of matrix metalloproteinases and extracellular matrix in human kidney mesangial cells

The glomerular mesangium contains mesangial cells which are embedded in the mesangial extracellular matrix. Under normal conditions, mesangial cells synthesize and degrade components of the extracellular matrix in a coordinated and balanced manner. The amount and composition of the mesangial extracellular matrix contributes to the structural and functional properties of the glomerulus. Mesangial cells are involved in glomerular injury in many renal diseases including excess aldosterone pathologies. We are studying the gene expression network that regulates mesangial cell proliferation and function in excess aldosterone pathological states. We are also analyzing the regulation of matrix metalloproteinases, the enzymes involved in extracellular matrix degradation and remodeling, by aldosterone in mesangial cells and their role in glomerulus remodeling.

Cardio-renal gene and miRNA expression regulation in aldosterone-mediated target organ injury

Animal studies have shown that excess aldosterone only causes deleterious effects in the presence of elevated salt intake. Unfortunately, human salt consumption is grossly elevated in modern societies generating a fertile ground for excess aldosterone to exert its deleterious effects. Despite the serious consequences of elevated aldosterone levels for human health the molecular mechanisms that mediate the onset and progression of excess aldosterone mediated target organ injury are not fully understood. We are studying whole genome gene expression of coding genes and microRNAs in an animal model of aldosterone/salt-mediated target organ injury that resembles the human pathological condition.

Cardio-renal mineralocorticoid receptor regulation in aldosterone-mediated target organ injury

The mineralocorticoid receptor (MR) is the receptor for aldosterone and plays a central role in excess aldosterone-mediated target organ injury. The MR has been reported to be subjected to transcriptional, translational and post-translational regulation including expression regulation, alternative splicing, alternative translation initiation sites, phosphorylation, sumoylation and neddylation . Furthermore, the MR has also been suggested to have potential sites for ubiquitination and acetylation. However, although these post-translational modifications suggest a broad repertoire of regulatory possibilities for the MR, most of them have only been reported to occur in vitro and in most cases using exogenous expression systems. Despite the serious consequences of excess aldosterone for human health and the central role of the MR in this pathological condition, little is known about MR regulation and its mechanisms of action that mediate the onset and progression of aldosterone-mediated target organ injury. We are studying MR regulation and its mechanisms of action in vivo in an animal experimental model of aldosterone-mediated target organ injury. We are analyzing MR expression, alternative splicing, post-translational modifications and MR-mediated gene expression regulation in aldosterone target organs including the heart and the kidney.