ProfessorOffice: G206Lab: G206Office: (601) 984-1523BibliographyEmail
The major research interests of my research team are:
Molecular mechanisms of aldosterone-mediated cardiac and renal injury and dysfunctionExcess aldosterone (ALDO) causes hypertension and cardiac hypertrophy, inflammation, fibrosis and dysfunction. Primary Aldosteronism is a human pathology characterized by the excess autonomous secretion of ALDO by the adrenal gland and is associated with severe cardio-renal damage. Primary Aldosteronism is the most common cause of secondary hypertension. Despite the prevalence of primary Aldosteronism and its deleterious consequences, the molecular mechanisms that mediate the onset and progression of ALDO-mediated cardiac and renal injury and dysfunction remain poorly understood.We use a variety of experimental models ranging from cells to whole animals and apply a range of molecular, cellular and physiology techniques to elucidate the genes, pathways and networks modulated by excess ALDO. We aim to elucidate potential targets that we can manipulate to abolish or mitigate the deleterious cardiac and renal effects of excess ALDO observed in patients with Primary Aldosteronism.Role and regulation of microRNAs in aldosterone-mediated cardiac and renal injury and dysfunctionMicroRNAs (miRNAs) are short endogenous non-coding RNAs that exert their biological effects by downregulating the expression levels of specific genes. Several microRNAs have been implicated in cardiovascular disease. However, the role of miRNAs in ALDO-mediated cardiac and renal injury and dysfunction remains largely unknown.We use animal experimental models of Primary Aldosteronism to elucidate the miRNAs regulated by excess ALDO in the cardiovascular and renal systems. Furthermore, we manipulate candidate target microRNAs by pharmacological or genetic means to elucidate the role of these particular microRNAs in the onset and progression of cardiac and renal injury triggered by excess ALDO. We aim to identify candidate miRNAs to manipulate them by pharmacological means to abolish or mitigate the deleterious cardiac and renal phenotype observed in patients with Primary Aldosteronism.Role of microRNAs in acetaminophen-induced acute liver failureAcute liver failure (ALF) is characterized by severe and sudden loss of hepatocellular function in patients with previously normal liver function, leading, in many cases, multiorgan system failure and death. In the US, drug-induced liver injury is the main cause of ALF, and acetaminophen (APAP) intoxication accounts for ~50% of the cases. Current therapies are suboptimal; therefore, alternative or complementary pharmacological interventions and therapies are desperately needed for individuals suffering from APAP-induced ALF. miRNAs, as a family, have been implicated in liver zonation but no individual candidates have been identified. Moreover, APAP-induced ALF is a zonal pathological event.We aim to identify miRNAs that temporally disrupting liver zonation, beside other possible mechanisms, may be manipulated by pharmacological means to abolish or mitigate the effects of APAP-induced ALF.
Role and regulation of microRNAs in depression and alcoholismThe treatment of depression and other mood and comorbid disorders is far from satisfactory in a majority of psychiatric patients. The difficulties in finding more effective treatments are to a great extent due to our incomplete understanding of the molecular and cellular mechanisms that operate in specific brain circuits such as those involving the prefrontal cortex, known to be highly relevant to the pathophysiology of depression, anxiety and addiction. microRNAs and their network of target regulated genes are an exciting area to explore to understand the basic biology of this disorders and to develop novel therapeutic approaches. We have found that microRNA-21 is preferentially expressed in the oligodendrocytes of the white matter of the prefrontal cortex. Furthermore, microRNA-21 expression is significantly decreased in the white matter of the prefrontal cortex of human subjects with depression.We aim to elucidate the regulation and role of microRNA-21 in the white matter of the prefrontal cortex in depression and alcoholism with the ultimate goal of designing novel therapeutic approaches for these devastating disorders.
Role and regulation of microRNAs in Polycystic Ovary SyndromePolycystic Ovary Syndrome (PCOS) is the most common endocrine disorder in reproductive age women. PCOS subjects suffer not only reproductive abnormalities but they are also prone to develop cardio-metabolic derangements such as obesity, insulin resistance, hypertension, and cardio-renal injury. MicroRNA-21 has been implicated in all of the above mentioned pathologies making it an attractive pharmacological target. Furthermore, therapeutic approaches to increase or decrease particular microRNAs are currently actively pursued in clinical trials and heading to the clinic.