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Search Results to Susan Smyth
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One or more keywords matched the following properties of
Smyth, Susan
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overview
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Inflammation and Thrombosis Program
Drawing on a long-standing interest in platelet biology, our group has established animal models for studying the role of platelet membrane proteins in thrombosis and the response to arterial injury, and has delineated specific signaling systems responsible for mediating platelet-leukocyte interactions and for inflammation in the context of arterial injury and cardiac hypertrophy. We are interested in understanding the functional interplay between thrombosis and inflammation. Our work has resulted in observations about beneficial effects of antiplatelet drugs in infectious and inflammatory states of pneumonia and sepsis. This work has also spawned clinical trials of the effects of antithrombotic therapy on inflammation and the identification of biomarkers of ischemic heart disease. Current funded work continues to identify novel signaling pathways in platelets, which likely will be the target for future translational studies.
Lysolipid Signaling Program
Our group also has a longstanding research interest in the role of bioactive lysophospholipid, such as lysophosphatidic acid (LPA), as mediators of cardiovascular disease. The lysophospholipase D autotaxin (ATX) catalyzes the hydrolysis of circulating or cell-associated lysophosphatidylcholine (LPC) to generate LPA, which has potent, receptor-mediated effects on blood and vascular cells. LPA is a proteotypic member of a family of bioactive lipid phosphoric acids that function as receptor-active mediators with roles in cell growth, differentiation, apoptosis and development. Our contributions to the literature includes characterizing pathways for production and metabolism of LPA in the circulation; providing the first evidence of a pathologic role for LPA receptors in the response to arterial injury; identifying key structural and functional elements of ATX and mechanisms for regulation of ATX function by localization along cell surfaces; demonstrating roles for specific LPA receptors in experimental atherosclerosis. Current work is focused on identifying mechanistic links between dietary intake of lipids and cardiovascular disease risk. Current investigations are exploring the possibility that choline-containing lipids and adipose-derived ATX serve as links between diet and cardiovascular disease risk.
LPA can hydrolyzed and inactivated by lipid phosphate phosphatase (LPP) enzymes present on cell membranes. A genome-wide association studies (GWAS) identified the PLPP3/PPAP2B gene encoding LPP3 as a novel loci associated with coronary artery disease susceptibility. We have established that LPP3 expression in mice is critical to attenuate inflammation, reduce smooth muscle cell proliferation, and maintain endothelial barrier function following vascular injury in an LPA-dependent manner. We have functionally validated that changes in LPP3 expression accelerates experimental atherosclerosis. Current studies are focused on understanding how heritable human variation in PLPP3 predisposes to the development of atherosclerosis and calcific aortic valve disease, which should translate identification of novel pathways for disease prevention.
Active Funding:
Serum Amyloid as a critical mediator between inflammation and thrombosis
BSR&D Senior Clinical Scientist Award
VA Merit I01BX004671
12/01/2019 - 9/30/2027
Smyth (PD/PI)
This grant explores mechanisms by which inflammation activated platelet function and heightens thrombosis.
Lysophosphatidic Acid and Cardiovascular Disease Risk
VA Merit I01BX005637
4/01/2020 - 12/31/2024
Morris and Smyth (MPI)
This grant seeks to understand the role of the ATX/LPA/LPP3 signaling nexus in the development of calcific aortic valve disease.
Cardiovascular Health effects of per- and polyfluorinated alkyl substances in the Millennium Cohort
MO2216/ Inter Agency Agreement
03/01/22-02/27/25
Morris (PI) Smyth (co-investigator)
This study will compare circulating levels of PFAS in military firefighters and construction workers and examine the relationship between PFAS, circulating lipids, other cardiovascular disease risk determinants and health outcomes.
Completed Awards as Principle Investigator:
Project MISSION: Developing a multicomponent, Multilevel Implementation Strategy for Syncope OptImalCare thrOugh eNgagement
NIH/NHLBI U01 HL143508
Li, Smyth, Williams (MPI)
This is a hybrid implementation – dissemination strategy to improve adherence to guideline directed care for patients with syncope
TL1 NRSA Training Core
NIH/NCATS 1TL1TR001997
8/15/16-5/31/26
Smyth (PI)
The objective of this grant is to train students, residents and fellows in clinical and translational research. After founding and successfully renewing the grant twice, I transferred it to another PI when I departed the institution in 2021.
Lipid phosphate phosphatase 3 as a novel atherosclerosis suppressor
NIH/NHLBI R01HL120507
4/01/15 – 3/31/21
Smyth and Morris (MPI)
The goal of this study was to functionally validate PLPP3, encoding lipid phosphate phosphatase 3, as a novel protector from atherosclerosis.
Clinical Scholars in Cardiovascular Science Training Grant
NIH/NHLBI T32HL091812
6/1/08 – 5/31/19
Smyth (PI)
The objective of this grant is to train clinicians (MD, PharmD, RN/PhD) to become independent cardiovascular scientists.
Adipose autotoxin and lysophosphatidic acid signaling
VA Merit Award BX002769
10/1/2014 – 9/30/2019
Smyth (PI)
The goal of this study was to study the role of adipose-derived autotoxin as a novel mediator of cardiovascular disease
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One or more keywords matched the following items that are connected to
Smyth, Susan
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- Platelet Aggregation Inhibitors
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