Dr. Jones is an professor in the Department of Surgery and a Research Health Scientist in the VA Research Service. Dr. Jones received his BA in Microbiology from the University of California San Diego, and his PhD in Biochemistry and Molecular Biology from the Medical University of South Carolina. He completed his graduate and post-doctoral training under Dr. Yusuf Hannun, studying protein-lipid interactions and sphingolipid signaling. Dr. Jones accepted a faculty appointment in the Division of Cardiothoracic Surgery in 2005. His research focuses on pathogenic mechanisms that drive extracellular matrix remodeling in the development of cardiovascular disease, with particular interest in thoracic aortic aneurysms.
Research in his laboratory focuses on the pathobiology of thoracic aortic aneurysms (TAAs), with a major goal to improve clinical care through advancements in diagnosis, prognosis, and treatment of TAA disease. TAAs often remain asymptomatic and are usually diagnosed serendipitously during routine physical examinations for other medical issues. The risk factors for developing a TAA are similar to those that contribute to heart disease, including a history of smoking, having hypertension, and having hypercholesteremia. Once detected, there is a paucity of therapeutic options other than surgical repair or endovascular stenting; neither of which address the underlying cause of aneurysm disease. As such, a “watch and wait” surveillance program is initiated until the risk of aortic rupture outweighs the risk of the surgical repair. Importantly, this period of surveillance provides a therapeutic opportunity during which treatment with medical therapy designed to reverse or reduce dilatation would be most advantageous.
Currently his reserch focuses on two primary areas: The first primary area is focused on understanding the role of microRNA-133a in TAA development. One class of cellular regulators gaining recognition as potentially useful diagnostics and therapeutics, are the microRNAs (miRs). These small, non-coding RNA segments can be detected in both tissue and plasma. Our previous work has demonstrated significant size-dependent changes in miR abundance in patient thoracic aortic aneurysm tissue; such that as aortic diameter increased, a subset of cellular miRs deceased in abundance. It was subsequently discovered that many of these miRs were packaged into exosomes and secreted from cells in a tension-dependent fashion. In the context of aortic aneurysm, the Law of Laplace suggests that wall-tension increases with aortic diameter, thus identification of these tension-sensitive miRs that are released in response to elevated wall-tension, may provide insights into the initiation and progression of aneurysm disease, and provide a wealth of information in terms of the signaling pathways that are altered during disease development. Moreover, preliminary evidence suggests that replacement of these miRs may be able to attenuate aneurysm development. Thus, current studies are focused on developing a novel cellular therapeutic to treat TAA, using miR-133a modified macrophages, and identifying the underlying mechanisms targeted by the microRNA.
The second primary area of study focuses on the role of stress and how it modifies aneurysm development. Numerous studies, among both Veterans and the general public, have shown that chronic psychological stress has been associated with poor health outcomes and increased risk of developing cardiovascular disease (CVD). Post-traumatic stress disorder (PTSD) has been shown to trigger a cascade of neuronal, hormonal, and immunologic responses that can cause and exacerbate a myriad of chronic physical ailments. Although the exact mechanism linking stress and CVD is unknown, it has been established that PTSD patients have significantly higher circulating pro-inflammatory cytokines and blood cell counts (white, red, platelets), as well as higher heart rates and blood pressures (BP) both at rest and in response to stimuli. Importantly, PTSD patients were found to have a higher prevalence of neurogenically-derived resistant hypertension (17% compared to 6%). These changes in BP, inflammatory state, and resistant hypertension are thought to be mediated, in part, by an amygdalo-hypothalamic pathway in the brain. This pathway has been shown to regulate BP and inflammation through inhibitory gamma-aminobutyric acid signaling neurons (or GABAergic circuits). In chronic stress, these circuits are attenuated leading to sympathetic overactivation. Thus, this project will examine the role of stress and neurogenic hypertension in aortic homeostasis and aortopathy and determine the underlying mechanisms linking stress to vascular disease in an effort to understand stress-dependent changes in aortic structure and composition.
The project areas will both provide exceptional insight into the development of TAA and may identify specific cell-types and novel signaling pathway that contribute TAA formation and progression, with the goal of attenuating aortic dilation to treat anerysm disease.