The broad objective of the University of Utah Molecular Medicine Translation Research Center in Thrombosis (U2M2-TRCT) is to dissect novel clinical and molecular determinants of thrombotic risk in patients with metabolic disorders (obesity, diabetes, and the metabolic syndrome). The U2M2-TRCT unites a group of basic and clinical investigators with breadth and expertise in thrombosis and metabolic dysregulation. Our studies will test the thematic hypothesis that metabolic changes in the systemic milieu reprogram platelet precursors and platelets themselves, resulting in altered thrombotic activities of these critical cells. To examin this central theme, we propose four research projects and four cores and studies by a cadre of established and emerging investigators with proven track records of productive interactions. The intellectual infrastructure is as follows: Project 1, The Molecular Regulation of Platelet Reprogramming by the Metabolic Milieu, characterizes reprogramming events in platelets and dissects the mechanisms by which microRNAs influence platelet phenotypes in metabolic syndromes;Project 2, Metabolic Regulation of Platelet Reprogramming, will determine how genetic manipulation of glucose transporters and modulators of mitochondrial function regulate reprogramming events and functional activities of platelets;Project 3, The Role of the Metabolic Milieu in Regulating Platelet Reprogramming in Humans, prospectively examines platelet reprogramming and platelet hyperreactivity imposed by the metabolic milieu of type 2 diabetes. Project 3 will also determine if therapeutic correction of metabolic imbalances reverses platelet reprogramming and hyperactivity;Project 4, Platelet Reprogramming in Human Obesity and Diabetes, will evaluate platelet reprogramming and function in subjects exposed to acute triglyceride emulsion infusion, obese subjects before and after bariatric surgery, and patients enrolled in the Framingham Heart Study. Screening of an early-phase translation mRNA nanochip in humans with metabolic syndromes is a key feature in Project 4. Together, our translational studies will explore new paradigms in thrombosis and metabolic syndromes, and will be a unique platform for research career development.

Public Health Relevance

Patients with type 2 diabetes, obesity, or the metabolic syndrome are at increased risk for blood clots (thrombosis) caused by cells called platelets. Our studies will determine how metabolic factors in the blood and tissues (the metabolic milieu), such as high glucose and lipids, make platelets more prone to induce thrombosis, providing new insights into the treatment and management of diabetes and obesity.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZHL1-CSR-C (F1))
Program Officer
Link, Rebecca P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Utah
Internal Medicine/Medicine
Schools of Medicine
Salt Lake City
United States
Zip Code
Manne, Bhanu K; Xiang, Shang Chun; Rondina, Matthew T (2017) Platelet secretion in inflammatory and infectious diseases. Platelets 28:155-164
Kapur, Rick; Kim, Michael; Rebetz, Johan et al. (2017) Low levels of interleukin-10 in patients with transfusion-related acute lung injury. Ann Transl Med 5:339
Rezania, Samin; Puskarich, Michael A; Petrusca, Daniela N et al. (2017) Platelet hyperactivation, apoptosis and hypercoagulability in patients with acute pulmonary embolism. Thromb Res 155:106-115
Stewart, Lauren K; Nordenholz, Kristen E; Courtney, Mark et al. (2017) Comparison of acute and convalescent biomarkers of inflammation in patients with acute pulmonary embolism treated with systemic fibrinolysis vs. placebo. Blood Coagul Fibrinolysis 28:675-680
Fidler, Trevor P; Middleton, Elizabeth A; Rowley, Jesse W et al. (2017) Glucose Transporter 3 Potentiates Degranulation and Is Required for Platelet Activation. Arterioscler Thromb Vasc Biol 37:1628-1639
Rodrigues, Rosana S; Bozza, Fernando A; Hanrahan, Christopher J et al. (2017) 18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury. Nucl Med Biol 48:52-62
Fidler, Trevor P; Campbell, Robert A; Funari, Trevor et al. (2017) Deletion of GLUT1 and GLUT3 Reveals Multiple Roles for Glucose Metabolism in Platelet and Megakaryocyte Function. Cell Rep 21:1705
Zeller Meidell, Krystin; Robinson, Ryan; Vieira-de-Abreu, Adriana et al. (2017) RGDfK-functionalized gold nanorods bind only to activated platelets. J Biomed Mater Res A 105:209-217
Michael, James V; Wurtzel, Jeremy G T; Mao, Guang Fen et al. (2017) Platelet microparticles infiltrating solid tumors transfer miRNAs that suppress tumor growth. Blood 130:567-580
Pannucci, Christopher J; Rondina, Matthew T (2017) Should we be following anti-factor Xa levels in patients receiving prophylactic enoxaparin perioperatively? Surgery 161:329-331

Showing the most recent 10 out of 95 publications