My career goal is to become an independent investigator in the biomedical science field and to make meaningful contributions to this field that help advance our knowledge and treatment strategies for cardiovascular disease. More immediately my aim is to make the transition from postdoctoral fellow to an independent research position. The excellent facilities within my Mentor?s laboratories, coupled the School of Medicine Departmental core facilities, as well as the support from the Associate Dean of Research provide an outstanding environment in which to undertake this training. My training and research plans emphasize the continual progression towards independence facilitating the eventual transition. This will be achieved through a number of approaches including didactic scientific training, a mentoring committee and set yearly goals. The proposed research plan is designed to provide molecular, cellular, tissue and whole animal techniques for the investigation of myocardial remodeling in response to a sustained increase in myocardial stress. This includes becoming competent in techniques that are new to me such as neuronal and fibroblast cell cultures, co-cultures, flow cytometry, as well as continuing to develop my skills in familiar techniques such as the blood-perfused isolated heart preparation. The proposal detailed herein is designed to provide a multifaceted experimental approach to examine the hypothesis that: myocardial remodeling, secondary to elevated myocardial stress, involves PAR-2-mediated stimulation of neuropeptides, which induce mast cell production of leukotrienes leading to myocardial remodeling. This will be examined using three specific aims: 1) to determine whether CGRP induces substance Pmediated maturation and activation of cardiac mast cells, leading to myocardial remodeling;2) to determine whether tryptase activation of PAR-2 causes cardiac mast cell maturation and activation and whether this is mediated by CGRP/substance P;and 3) to determine whether leukotrienes are a mechanism by which mast cells mediate myocardial remodeling.
In heart failure, the heart enlarges until it can no longer effectively pump sufficient amounts of blood around the body. This proposal will investigate the causes that initiate this enlargement. Once the causes are identified, drugs can be developed to treat this problem.
|Li, Jianping; Jubair, Shaiban; Levick, Scott P et al. (2016) THE AUTOCRINE ROLE OF TRYPTASE IN PRESSURE OVERLOAD-INDUCED MAST CELL ACTIVATION, CHYMASE RELEASE AND CARDIAC FIBROSIS. IJC Metab Endocr 10:16-23|
|MelÃ©ndez, Giselle C; Manteufel, Edward J; Dehlin, Heather M et al. (2015) Non-human primate and rat cardiac fibroblasts show similar extracellular matrix-related and cellular adhesion gene responses to substance P. Heart Lung Circ 24:395-403|
|Jubair, Shaiban; Li, Jianping; Dehlin, Heather M et al. (2015) Substance P induces cardioprotection in ischemia-reperfusion via activation of AKT. Am J Physiol Heart Circ Physiol 309:H676-84|
|Janicki, Joseph S; Brower, Gregory L; Levick, Scott P (2015) The emerging prominence of the cardiac mast cell as a potent mediator of adverse myocardial remodeling. Methods Mol Biol 1220:121-39|
|Dehlin, Heather M; Levick, Scott P (2014) Substance P in heart failure: the good and the bad. Int J Cardiol 170:270-7|
|Levick, Scott P; Goldspink, Paul H (2014) Could interferon-gamma be a therapeutic target for treating heart failure? Heart Fail Rev 19:227-36|
|Janicki, Joseph S; Spinale, Francis G; Levick, Scott P (2013) Gender differences in non-ischemic myocardial remodeling: are they due to estrogen modulation of cardiac mast cells and/or membrane type 1 matrix metalloproteinase. Pflugers Arch 465:687-97|
|Li, Jianping; Levick, Scott P; DiPette, Donald J et al. (2013) Alpha-calcitonin gene-related peptide is protective against pressure overload-induced heart failure. Regul Pept 185:20-8|
|Dehlin, Heather M; Manteufel, Edward J; Monroe, Andrew L et al. (2013) Substance P acting via the neurokinin-1 receptor regulates adverse myocardial remodeling in a rat model of hypertension. Int J Cardiol 168:4643-51|
|McLarty, Jennifer L; MelÃ©ndez, Giselle C; Brower, Gregory L et al. (2011) Tryptase/Protease-activated receptor 2 interactions induce selective mitogen-activated protein kinase signaling and collagen synthesis by cardiac fibroblasts. Hypertension 58:264-70|