Camire Laboratory

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The formation of a blood clot following an injury is a critically important host defense mechanism. Precise control of this system is critical for survival in all higher animals with a circulatory system.

The Camire Lab is interested in the molecular and cellular processes contributing to and regulating blood coagulation. These integrated pathways have a major impact on human health and disease, as failure of this system to respond appropriately can lead to life-threatening bleeding or thrombosis. The lab is interested in questions related to the enzymology, biochemistry, and molecular genetics of enzyme complexes involved in blood coagulation.

Using a combination of kinetic, biophysical, and structural techniques in conjunction with the expression of well characterized recombinant blood clotting proteins, the lab gains insight into how proteins involved in the production of thrombin assemble and function within macromolecular enzyme complexes. Furthermore, the lab employs biological models to evaluate hemostasis in vivo and investigate new therapies for treating bleeding disorders. 

Specifically, the Camire Lab studies questions related to the enzymology, biochemistry, and molecular genetics of enzyme complexes involved in blood coagulation. The lab is specifically interested in how clotting factors V, VIII, IX, and X function and are regulated in the blood. Numerous systems are employed to investigate these questions including kinetic, biophysical, and structural approaches in addition to using in vivo mouse models to make meaningful contributions to the field.

Project Highlights

  • Molecular basis of procofactor activation: The Camire Lab is interested in understanding how FV and FVIII are preserved as inactive procofactors and defining their mechanism of activation. The lab's work has uncovered surprising and unexpected observations that have fundamentally shifted current thinking about FV activation and its regulation by TFPI.
  • Structural correlates of protease function-basic and translational research: The lab seeks to better understand how processing of inactive serine protease zymogens such as FX and FIX, to their active forms contribute to the expression of binding sites critical to their function. Knowledge from these biochemical studies has been applied to translational studies, some in collaboration with companies, to develop novel protein therapeutics to treat bleeding in hemophilia, trauma, or other conditions.
  • Imaging coagulation reactions in vivo. The lab has taken advantage of fluorescence approaches developed for physical studies of coagulation enzyme function to develop enabling technologies that permit quantitative measurements of enzyme complex assembly and function in vivo
  • Employ protein, gene therapy, and other strategies to alleviate hemophilia A or B. Using different bioengineering strategies, the Camire Lab is interested in modifying FVIII or FIX with unique properties that could be useful in a gene-based approach.
Leader

Rodney M. Camire, PhD

Investigator
Dr. Camire's research focuses on understanding the components of the blood coagulation system, how they interface with activated cells, and how disturbances in their function lead to bleeding and thrombosis. He is also interested in developing novel therapeutic approaches (protein, gene-based, small molecule) to mitigate these events, which are major causes of morbidity and mortality worldwide.