Hematology Division

Thomas J. Girard, PhD

Assistant Professor
Department of Medicine
Hematology Division

Research Interests

  • Blood coagulation
  • Tissue factor pathway inhibitor
  • Protein Z-dependent protease inhibitor


  • (314) 362-8863 (tel)
  • (314) 362-8826 (fax)
  • Room 8804 Clinical Sciences Research Building (lab)
  • Hematology Division
    Campus Box 8125
    Washington University School of Medicine
    660 South Euclid Avenue
    St. Louis, MO  63110


Blood coagulation involves a highly regulated balance between pro-coagulant and anti-coagulant activities. An imbalance that favors pro-coagulation leads to thrombotic events such as strokes and myocardial infarctions. An imbalance that favors anti-coagulation leads to bleeding, as is the case in hemophilia. Our laboratory studies two endogenous regulators of blood coagulation, tissue factor pathway inhibitor (TFPI) and protein Z-dependent protease inhibitor (ZPI).

Tissue factor (TF), the key initiator of coagulation, is found to be constitutively expressed on the outer surface of vessels, sequestered from direct contract with blood. Upon vascular injury, TF exposure to blood triggers coagulation to abate bleeding. TF binds activated factor VII (FVIIa) and the TF/FVIIa catalytic complex activates FX to FXa and FIX to FIXa leading to thrombin generation and formation of a fibrin clot. Besides initiating coagulation, TF exposure mediates cell-signaling effects directly through TF-dependent cell surface complexes and indirectly through the actions of thrombin and FXa generated down-stream in the coagulation process. While critical for hemostasis, TF expression induced by inflammation, and often, TF aberrantly expressed on tumor cells also plays a deleterious role in pathologic conditions such as thrombosis, inflammation, tumor growth and metastasis.

The primary focus of our research is TFPI, which is the main endogenous regulator of TF/FVIIa activity. TFPI is a multivalent FXa-dependent inhibitor of TF/FVIIa, and protein S-enhanced direct inhibitor of FXa. As such TFPI is critical to maintain a hemostatic balance and likely reduces the deleterious role of TF in disease. TFPI is produced as multiple isoforms, with distinct locations and functions. We are using CRISPR/Cas9 technologies to generate TFPI isoform-specific knockout mice and using these mice to evaluate the contributions of each isoform to hemostasis and to TF-related diseases.

The secondary focus of our research is ZPI, which is a protein Z-dependent inhibitor of coagulation FXa. We have recently found that deletion of PZ or ZPI in hemophilic mice reduces bleeding and that antibodies to PZ and ZPI enhance coagulation in human hemophiliac plasma. Similar results are seen by depletion of TFPI activity. We are evaluating in mice if blockade of PZ, ZPI or a particular isoform of TFPI may be a viable alternative treatment for hemophilia.


Hemostatic Balance