BLRD Research Career Scientist Award Application

Project Summary For nearly two decades, the Lazartigues Lab has focused on deciphering the cellular and molecular processes behind the compensatory renin-angiotensin system's role in cardiovascular and metabolic regulation. Our aim is to leverage this understanding to address the cardiovascular and metabolic risks associated with hypertension and diabetes in Veterans and other patients suffering from these diseases. Through collaboration with local, national, and international experts and employing a multidisciplinary approach, we have investigated the role of the compensatory renin-angiotensin system in the neurocircuits involved in autonomic nervous system regulation. This research sheds light on how specific hypothalamic neurons influence autonomic nervous system function, impacting blood pressure control in health and disease. The support from the VA BLRD service has been instrumental in gaining recognition for our research. Our work on ACE2 internalization, which has significant implications for understanding SARS-CoV-2 infection—particularly relevant to Veterans—highlights our commitment to advancing knowledge and treatment strategies for cardiometabolic diseases. Our lab has made significant strides in understanding the compensatory renin-angiotensin system’s role in cardiometabolic diseases. Notable achievements include discovering mechanisms of ACE2 loss, such as ACE2 shedding by ADAM17 and ACE2 ubiquitination. These findings, initially published in Circulation Research (2013) and Hypertension (2014), have been critical in explaining the SARS-CoV-2 virus' mechanism of infection and earned recognition from the NIH Director’s Office with a Transformative Research Award. Our work is regularly featured in top-tier journals, and our trainees have garnered accolades from the American Physiological Society and the American Heart Association. The goals of our lab for the Proposed Award Period are to: Investigate the Compensatory Renin-Angiotensin System: Further explore its central role in regulating autonomic, metabolic, and cardiovascular functions. This research aims to identify molecular mechanisms that could be targeted for treating diabetes and hypertension, conditions prevalent among Veterans. Mentor Emerging Researchers: Provide guidance and support to young scientists, both basic and clinical, to cultivate their potential as future biomedical researchers. This effort is crucial for advancing medical research and improving Veterans' health. Serve the Scientific Community and VA System: Contribute to the SouthEast Louisiana Veterans HealthCare System, LSU Health-New Orleans, and the broader scientific community through teaching, committee service, and organizing research initiatives and events.