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.
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.
|Rondina, Matthew T; Tatsumi, Kohei; Bastarache, Julie A et al. (2016) Microvesicle Tissue Factor Activity and Interleukin-8 Levels are Associated with Mortality in Patients with Influenza A/H1N1 Infection. Crit Care Med 44:e574-8|
|Freedman, Jane E; Gerstein, Mark; Mick, Eric et al. (2016) Diverse human extracellular RNAs are widely detected in human plasma. Nat Commun 7:11106|
|Yoo, Jae Hyuk; Shi, Dallas S; Grossmann, Allie H et al. (2016) ARF6 Is an Actionable Node that Orchestrates Oncogenic GNAQ Signaling in Uveal Melanoma. Cancer Cell 29:889-904|
|Yost, Christian C; Schwertz, HansjÃ¶rg; Cody, Mark J et al. (2016) Neonatal NET-inhibitory factor and related peptides inhibit neutrophil extracellular trap formation. J Clin Invest 126:3783-3798|
|Koliopoulou, Antigone; McKellar, Stephen H; Rondina, Matthew et al. (2016) Bleeding and thrombosis in chronic ventricular assist device therapy: focus on platelets. Curr Opin Cardiol 31:299-307|
|Stubblefield, William B; Alves, Nathan J; Rondina, Matthew T et al. (2016) Variable Resistance to Plasminogen Activator Initiated Fibrinolysis for Intermediate-Risk Pulmonary Embolism. PLoS One 11:e0148747|
|Shih, Lauren; Kaplan, David; Kraiss, Larry W et al. (2016) Platelet-Monocyte Aggregates and C-Reactive Protein are Associated with VTE in Older Surgical Patients. Sci Rep 6:27478|
|AraÃºjo, ClÃ¡udia V; Campbell, Clarissa; GonÃ§alves-de-Albuquerque, Cassiano F et al. (2016) A PPARÎ³ AGONIST ENHANCES BACTERIAL CLEARANCE THROUGH NEUTROPHIL EXTRACELLULAR TRAP FORMATION AND IMPROVES SURVIVAL IN SEPSIS. Shock 45:393-403|
|Rowley, Jesse W; Chappaz, StÃ©phane; Corduan, AurÃ©lie et al. (2016) Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood 127:1743-51|
|Beaulieu, Lea M; Vitseva, Olga; Tanriverdi, Kahraman et al. (2016) Platelet functional and transcriptional changes induced by intralipid infusion. Thromb Haemost 115:1147-56|
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