Bovill Bio
Dr. Bovill's laboratory is involved in both clinical and basic science research. His clinical research is focused on vitamin K dependent hemostasis and the therapeutic use of thrombolytic agents.
Protein C Deficiency
Dr. Bovill's laboratory has described a number of Vermont kindreds with protein C deficiency. A large family in southern Vermont was found to have a mutation in the amino terminal Gamma Carboxy Glutamic Acid (Gla) domain of the protein C molecule. This was the first described Gla domain mutation in a protein C deficient kindred. Interestingly, in this family, the abnormal allelic product was fully expressed and present in the plasma. It was consequently possible to study the profound structure function changes caused by this mutation in the family. Another large kindred in northern Vermont whose pedigree is demonstrated in the figure below, is the largest single family with protein C deficiency reported in the literature. The mutation present in this family is His 107 Pro with a downstream stop codon which leads to the potential formation of a truncated protein, although no evidence for this was found in the family. Of interest in this family, is the evidence for another abnormality, in addition to the protein C deficiency, in the genesis of thrombosis. The present focus of investigation involves an expansion of the analysis of this French Canadian kindred into Quebec with the application of candidate gene and/or linkage analysis to further understand the mechanism underlying the thrombotic diathesis in this family.
Neonatal Vitamin K Dependent Hemostasis
Dr. Bovill, in collaboration with Dr. Roger Soll in the Department of Pediatrics, has evaluated vitamin K dependent hemostasis in neonates. This evaluation utilizes unique monoclonal antibodies characterized to identify the descarboxy forms of the vitamin K dependent proteins. Drs. Bovill and Soll demonstrated that a large proportion of normal and pre-term neonates have descarboxy forms of both protein C and prothrombin present at birth. Subsequent studies demonstrated that the descarboxy in protein C persisted to three days following the prophylactic use of vitamin K at birth, despite the short half life of the protein. This latter observation gives the first evidence that there is immaturity of the hepatic carboxylase system, as well as vitamin K deficiency underlying the production of abnormal descarboxy vitamin K dependent proteins in neonates. These abnormalities of neonatal hemostasis may well play a role in the onset of such complications as intraventricular hemorrhage. Clinical preventive studies are presently being designed at UVM.
Anticoagulant Therapy
Dr. Bovill is involved in a large multicenter clinical trial called SPAF-3 evaluating the effect of warfarin and/or aspirin on stroke in patients with fibrillation. This large clinical trial involves the prospective assessment of the clinical utility of thrombin and platelet inhibition utilizing modern hemostatic markers. He is also involved in a number of pre-clinical and clinical studies of novel anticoagulants directed against activated coagulation enzymes.
Fibrinolytic Therapy
Dr. Bovill has extensive experience in large clinical trials involving thrombolytic agents. He works closely with Dr. Russell Tracy at the Laboratory for Clinical Biochemistry Research at the UVM Colchester Research Facility. This research facility has been the center for the direction of ancillary hemostasis studies in the TAMI, TIMI-II, TIMI-III, and GUSTO, large collaborative clinical trials of thrombolytic agents. Over the past eight years, these studies have involved upwards of 30,000 patients from around the world.
