Overview of Current Research Programs:
The focus of our research program derives from unique opportunities many of us have had by training formally in two traditionally divergent investigative areas in the cardiovascular sciences - classical experimental physiology/pharmacology and molecular genetics. Our research efforts are concentrated at the intersection of these disciplines, in the realm of functional genomic analysis of the cardiovascular system. Our studies examine the physiological and pathophysiological effects of targeted genetic alterations in animals (both germline and somatic) in order to ultimately unravel the complex molecular mechanisms determining normal cardiovascular function and the pathogenesis of certain cardiovascular diseases. Within this framework, we focus on three major areas:
- Central neural control of blood pressure and autonomic function, with an emphasis on dissection of gene function in cardiovascular regulatory circuits of the brain in normal animals and in clinically relevant models of hypertension.
- Molecular determinants of cardiac disease, particularly cardiac hypertrophy and heart failure.
- Molecular pathophysiology of preeclampsia using a novel genetic mouse model that spontaneously develops the cardinal features of this pregnancy-induced hypertensive disorder.
Common themes linking all of our projects are the renin-angiotensin system and the role of oxidative stress.
Major Projects: (click on each title for more information)
- Regional and cellular significance of the brain renin-angiotensin system (RAS) in hypertension.
- Oxidant mechanisms in central neural control of blood pressure.
- Hypertension and prostanoid signaling in the subfornical organ of the brain.
- Role of redox-mediated activation of NFkB and AP-1 in neurogenic hypertension.
- Oxidative stress-induced neuro-cardiovascular dysfunction in myocardial infarction-induced heart failure.
- Molecular pathogenesis of preeclampsia.
- Role of reactive oxygen species in the regenerative capacity of c-Kit+ cardiac precursor cells.
Unique Molecular, Physiologic and Imaging Tools Used in Our Research: (click on each title for more information)
- Targeted viral delivery of genes to specific cardiovascular circuits in mouse brain.
- Conditional gene deletion in specific neural axes using the Cre-loxP system.
- RNA interference strategies for localized gene silencing in cardiovascular tissues in vivo.
- Gene and miRNA arrays.
- Multiple genetic and experimental murine models of cardiovascular disease.
- Longitudinal non-invasive measurements of blood pressure, autonomic function and baroreflex in mice using radiotelemetry.
- High-frequency ultrasound measurement of heart function and fetoplacental status using Vevo 770.
- In vivo bioluminescence imaging.