Andrew Weyrich

Professor of Medicine and
Adjunct Professor in Pathology

Andy Weyrich

B.S. Baldwin-Wallace College

Ph.D. Bowman Gray School of Medicine

Research

References

andy.weyrich@u2m2.utah.edu

Andrew Weyrich's Lab Page

Andrew Weyrich's PubMed Literature Search

Research

Our laboratory investigates molecular mechanisms that regulate cell/cell interactions, cell signaling, and gene expression in the inflammatory and hemostatic systems, and how these events become dysregulated in human diseases. The studies are broadly applicable to a variety of organ systems and disease processes, including atherosclerosis, diabetes, and sepsis. In previous work, we identified how key adhesion adhesion molecules on the surface of platelets induce gene expression pathways in target leukocytes. These studies also led to the unexpected discovery that platelets, which circulate without a nucleus, splice precursor mRNA and translate mature mRNA into protein.

Our group is currently using interrogation of cDNA libraries in combination with polyribosome analysis and other assays of specialized translational control, proteomic strategies, assays of mRNA splicing and stability, novel imaging methods, and cell biologic approaches to dissect pathways and consequences of expression of key genes in informative models (primary human leukocytes, platelets, endothelial cells, and human hematopoetic stem cells differentiated to specific mature cell phenotypes). In addition, our group co-directs a parallel group of projects that utilize genetically-altered mice to examine thrombosis and inflammation responses in vivo. The in vivo studies are performed in collaboration with Drs. Dean Li and Guy Zimmerman. In parallel studies at the bench, our group has ongoing investigations of cellular activities and phenotypes in inflammatory and thrombotic syndromes in human patients. Current projects include studies of novel platelet responses in sepsis and diabetes. A different group of studies involves infants with neonatal necrotizing enterocolitis and other neonatal inflammatory syndromes. The unifying feature of these disorders is dysregulated inflammation and hemostasis. Clinical fellows, post-doctoral fellows, graduate students, and junior faculty participate in each of these "bedside" studies, which serve as a basis for research career development awards. Thus, students and fellows in our group are exposed to parallel lines of investigation that employ modern biologic, genomic, and proteomic approaches using both in vitro and in vivo models. Discoveries using these tools are then extended to questions of human inflammatory, thrombotic, and pulmonary diseases in a translational fashion.

References

  1. Rondina MT, Brewster B, Grissom CK, Zimmerman GA, Kastendieck DH, Harris ES, Weyrich AS (2012) In Vivo Platelet Activation in Critically-Ill Patients with Primary H1N1 Influenza. Chest, 41(6):1490-5
  2. Harris ES, Smith TL, Springett GM, Weyrich AS, Zimmerman GA (2012) Leukocyte adhesion deficiency-I variant syndrome (LAD-Iv, LAD-III): molecular characterization of the defect in an index family. Am J Hematol, 87(3):311-3
  3. Kraemer BF, Campbell RA, Schwertz H, Cody MJ, Franks Z, Tolley ND, Kahr WH, Lindemann S, Seizer P, Yost CC, Zimmerman GA, Weyrich AS (2011) Novel anti-bacterial activities of β-defensin 1 in human platelets: suppression of pathogen growth and signaling of neutrophil extracellular trap formation. PLoS Pathog, 7(11):e1002355
  4. Vieira-de-Abreu A, Campbell RA, Weyrich AS, Zimmerman GA (2011) Platelets: Versatile effector cells in hemostasis, inflammation, and the immune continuum. Semin Immunopathol, 34(1):5-30
  5. Kahr WHA, Hinckley J, Li L, Schwertz H, Christensen H, Rowley JW, Pluthero FG, Urban D, Fabbro S, Nixon B, Gadzinski R, Storck M, Wang K, Ryu G-Y, Jobe SM, Schutte BC, Moseley J, Loughran NB, Parkinson J, Weyrich AS, Di Paola J (2011) Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nature Genetics, 43(8):738-40
  6. Cecchetti L, Tolley ND, Michetti N, Bury L, Weyrich AS, Gresele P (2011) Megakaryocytes differentially sort mRNAs for matrix metalloproteinases and their inhibitors into platelets: a mechanism for regulating synthetic events. Blood, 118(7):1903-11
  7. Rowley JW, Oler A, Tolley ND, Hunter B, Low EN, Nix DA, Yost CC, Zimmerman GA, Weyrich AS (2011) Genome wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood, 118(14):e101-11
  8. Smith TL, Weyrich AS (2011) Platelets as central mediators of systemic inflammatory responses. Thromb Res, 127:391-394
  9. Rondina MT, Schwertz H, Harris ES, Kraemer BF, Campbell RA, Mackman N, Grissom CK, Weyrich AS, Zimmerman GA (2011) The septic milieu triggers expression of spliced tissue factor mRNA in human platelets. J Thromb Haemost,  9:748-758
  10. Schubert S, Schwertz H, Weyrich AS, Franks ZG, Lindemann S, Otto M, Behr H, Loppnow H, Schlitt A, Russ M, Presek P, Werdan K, Buerke M (2011) Staphylococcus aureus α-toxin triggers the synthesis of B-cell lymphoma 3 by human platelets. Toxins, 3:120-133
  11. Schwertz H, Weyrich AS (2010) Platelet precursors display bipolar behavior. J Cell Biol, 191:699-700
  12. Franks ZG, Campbell RA, Weyrich AS, Rondina MT (2010) Platelet-leukocyte interactions link inflammatory and thromboembolic events in ischemic stroke. Ann N Y Acad Sci, 1207:11-17
  13. Schwertz H, Köster S, Kahr WH, Michetti N, Kraemer BF, Weitz DA, Blaylock RC, Kraiss LW, Greinacher A, Zimmerman GA, Weyrich AS (2010) Anucleate platelets generate progeny. Blood, May 6;115(18):3801-3809
  14. Yost CC, Cody MJ, Harris ES, Thornton N, McInturf AM, Martinez MM, Chandler NB, Rodesch CK, Albertine KH, Weyrich AS, Zimmerman GA (2009) Impaired neutrophil extracellular trap (NET) formation and defective extracellular bacterial killing – A novel deficiency of innate immunity in neonatal polymorphonuclear leukocytes. Blood, 113:6419-6427
  15. Weyrich AS, Schwertz H, Kraiss LW, Zimmerman GA (2008) Protein synthesis by platelets: historical and new perspectives. J Thrombosis and Haemostasis, 7:241-246
  16. Weyrich AS, Denis MM, Schwertz H, Tolley ND, Foulks J, Spencer E, Kraiss LW, Albertine KH, McIntyre TM, Zimmerman GA (207) Bcl-3 synthesis via mTOR controls the retraction of fibrin clots by activated human platelets. Blood, 109:1975-1983
  17. Schwertz H, Tolley ND, Foulks JM, Denis MM, Risenmay BW, Buerke M, Tilley RE, Rondina MT, Harris EM, Kraiss LW, Mackman N, Zimmerman GA, Weyrich AS (2006) Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets. J Exp Med, 203:2433-2440
  18. Denis MM, Tolley ND, Bunting M, Schwertz H, Jiang H, Lindemann S, Yost CC, Rubner FJ, Albertine KH, Swoboda KJ, Fratto CM, Tolley E, Kraiss LW, McIntyre TM, Zimmerman GA, Weyrich AS (2005) Escaping the nuclear confines: signal dependent pre-mRNA splicing in anucleate platelets. Cell, 122:379-391

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Last Updated: 8/5/14