Thrombosis, Hemostasis, Vascular Biology / Immunobiology

Our focus is understanding the role of the blood coagulation system in general, and the biological functions of the natural Thrombomodulin (Thbd) – protein C anticoagulant pathway, in particular. Current projects investigate the cellular and molecular mechanisms by which these physiological mechanisms affect the host response to bacterial infections, control the development of the placenta, regulate the activation of the blood coagulation system, and affect recovery of the hematopoietic system from injury and stress. Insights into the physiological functions of the protein C system in these contexts are used to explore the potential for therapeutic interventions targeting this pathway in diseases like severe sepsis, malaria, bone marrow failure after exposure to lethal doses of radiation, and in other progenitor cell-driven processes of tissue remodeling after injury.

In collaborative studies with Investigators at MCW and the Blood Research Institute, we investigate the function of a protein (Gmap5) that has been linked to the development of autoimmune type 1 diabetes. We found in mouse models that this protein has a critical role in hematopoiesis and cell survival. Current research aims at delineating the biological mechanisms regulated by Gimap5 during hematopoiesis, and understanding how a defect in this gene might be causing autoimmune disease.

Dr. Weiler directs the joint Transgenic Core Facility of the Medical College of Wisconsin (MCW) and the Blood Research Institute / Blood Center of Wisconsin. The facility provides a wide range of services facilitating the generation, maintenance, and acquisition of genetically altered mice and rats.

• R01 HL133348, Regulation of Innate Immunology by Coagulation Receptors (07/01/2016 - 04/30/2020)
• P01 HL044612, Core C, Molecular and Cellular Mechanisms in Transfusion Medicine (12/01/2010 - 11/30/2015)
• R01 HL130678, Discovery of novel vascular therapies targeting PfEMP1-mediated cytoadhesion in severe malaria (09/15/2015 - 05/31/2019
• R01 HL117132, Protein C pathway function in Hematopoiesis (04/09/2014 - 03/31/2018)
• Pilot Grant, Clinical and Translational Science Institute of Southeast Wisconsin (04/01/2015 - 03/31/2016)

Complete List of Publications in MyNCBI Bibliography

Selected Publications

• Liang H, Kerschen E, Hernandez I, Basu S, Zogg M, Botros F, Jia S, Hessner MJ, Griffin JH, Ruf W, Weiler H. EPCR-dependent PAR2 activation by the blood coagulation initiation complex regulates LPS-triggered interferon responses in mice. Blood (2015) [in press]
• Kerschen E, Hernandez I, Zogg M, Maas M, Weiler H. Survival advantage of heterozygous fV Leiden carriers in murine sepsis. J Thromb Haemost (2015) [in press]
• Dinarvand P, Hassanian SM, Weiler H, Rezaie AR. Intraperitoneal administration of activated protein C prevents postsurgical adhesion band formation. Blood. 2015 [Epub ahead of print Jan 9, 2015].
• Cossette SM, Gastonguay AJ, Bao X, Lerch-Gaggl A, Zhong L, Harmann LM, Koceja, C, Miao RQ, Vakeel P, Chun C, Li K, Foeckler J, Bordas M, Weiler H, Strande J, Palecek SP, Ramchandran R. Sucrose non-fermenting related kinase enzyme is essential for cardiac metabolism. Biol Open. 2014 [Epub ahead of print].
• de Boer J, Kager LM, Roelofs J, Meijers J, de Boer OJ, Weiler H, Isermann B, van T Veer C, van der Poll T. Overexpression of activated protein C hampers bacterial dissemination during pneumococcal pneumonia. BMC Infect Dis. 14(1):559 (2014)
• Kager LM, Wiersinga WJ, Roelofs JJ, de Boer OJ, Weiler H, van 't Veer C, van der Poll T. A thrombomodulin mutation that impairs active protein C generation is detrimental in severe pneumonia-derived gram-negative sepsis (melioidosis). PLoS Negl Trop Dis. 2014 Apr 24;8(4):e2819. (2014)
• Fahs SA, Hille MT, Shi Q, Weiler H, Montgomery RR. A conditional knockout mouse model reveals endothelial cells as the predominant and possibly exclusive source of plasma factor VIII. Blood 123: 3706-3713 (2014)
• Yokota N, Zarpellon A, Chakrabarty S, Bogdanov VY, Gruber A, Castellino FJ, Mackman N, Ellies LG, Weiler H, Ruggeri ZM, Ruf W. Contributions of thrombin targets to tissue factor-dependent metastasis in hyperthrombotic mice. J Thromb Haemost. 12:71-81. (2014)
• Kager LM, Wiersinga WJ, Roelofs JJ, de Boer OJ, Weiler H, van 't Veer C, van der Poll T. A thrombomodulin mutation that impairs active protein C generation is detrimental in severe pneumonia-derived gram-negative sepsis (melioidosis). PLoS Negl Trop Dis. 2014 Apr 24;8(4):e2819. (2014)
• Borissoff JI, Otten JJ, Heeneman S, Leenders P, van Oerle R, Soehnlein O, Loubele ST, Hamulyák K, Hackeng TM, Daemen MJ, Degen JL, Weiler H, Esmon CT, van Ryn J, Biessen EA, Spronk HM, ten Cate H. Genetic and Pharmacological Modifications of Thrombin Formation in Apolipoprotein E-deficient Mice Determine Atherosclerosis Severity and Atherothrombosis Onset in a Neutrophil-Dependent Manner. PLoS One. 2013;8(2):e55784. (Epub 2013 Feb 7)
• Cheng TL, Wu YT, Lai CH, Kao YC, Kuo CH, Liu SL, Hsu YY, Chen PK, Cho CF, Wang KC, Lin WL, Chang BI, Chen CM, Weiler H, Shi GY, Wu HL. Thrombomodulin regulates keratinocyte differentiation and promotes wound healing. J Invest Dermatol. 133: 1638-1645 (2013)

Recruitment Flier