Research Program–
Hemostasis and Inflammation

Thrombosis associated with acute inflammation results from the up-regulation of coagulation and down-regulation of anti-coagulation and fibrinolysis.  Thus, hemostasis and inflammation are closely linked and contribute to the genesis of a number of diseases.

This research program utilizes multidisciplinary approaches to investigate the role of hemostasis in inflammatory-based diseases.  The Center currently houses over 80 strains of transgenic and gene knock-out mice which are used to define relationships between proteins of hemostasis and the development and progression of acute and chronic inflammatory-mediated diseases, e.g., asthma, atherosclerosis, and sepsis.

Asthma is the result of allergen-induced chronic inflammation to the bronchial tubes.  Recent studies in the Keck Center are defining new roles of proteins traditionally associated with blood coagulation in airway wall thickening and mucin production.

Atherosclerosis is initiated by an inflammatory lesion, which progresses to fatty streak formation, neointimal hyperplasia, and eventually vascular occlusion.  Studies in the Center have implicated fibrinogen in accelerating LDL cholesterol-driven atherosclerosis utilizing a mouse model that mimics human type IIa hyperlipidemia, the most common form of atherosclerosis.  This clinically relevant model is being used to study the roles of other hemostasis proteins in regulating pathologies of this disease.

Sepsis is a systemic inflammatory disease initiated by toxins associated with a bacterial infection, which can lead to hypotension, organ failure, and death if not properly controlled.  Investigations in the Keck Center utilize both in vivo and cell-based techniques to determine the role of components of hemostasis in the progression of this disease.

Research Program Investigators

 Recent Publications

Iwaki T, Sandoval-Cooper MJ, Tenenhouse HS, Castellino FJ.  (2008).  A missense mutation in the sodium phosphate co-transporter slc34al impairs phosphate homeostasis.  J. Am. Soc. Nephrol. 19:1753-1762.

Shinagawa K, Martin JA, Ploplis VA, Castelllino FJ.  (2007).  Coagulation factor Xa modulates airway remodeling in a murine model of asthma.  Am. J. Respir. Crit. Care Med. 175:136-143.

Lay AJ, Donahue D, Tsai MJ, Castellino FJ.  (2007).  Acute inflammation is exacerbated in mice genetically predisposed to a severe protein C deficiency.  Blood 108:1984-1991.