Research at the
FRANCIS OWEN BLOOD RESEARCH LABORATORY
 
Timothy C. Nichols, M.D., Director
Thomas H. Fischer, Ph.D., Scientific Director
 
Mission
 
The mission of The Francis Owen Blood Research Laboratory (FOBRL) is to reduce human suffering from bleeding, thrombosis and atherosclerosis by the study of unique, genetically defined porcine and canine models of these diseases. The primary strategy is to foster independent and collaborative study of these models by providing careful, humane care and breeding of the animals. As such, the FOBRL functions as a primary research laboratory conducting independent investigations utilizing these unique animal models and as a core laboratory making these animals available for collaborative studies with investigators at UNC and elsewhere. Most importantly, the FOBRL provides state of the art teaching and training for undergraduate and graduate students, post doctoral research fellows, and independent investigators.
 
Summary of Research Programs
 
 
 

Atherogenesis:

  • von Willebrand factor and shear forces in atherogenesis
  • Intracellular signaling connecting ras-related proto-oncogenes, the transcription factor NF-kB, inflammation and thrombosis
  • Development of gene therapies for inhibiting atherosclerosis
  
      Gene transfer to atherosclerotic plaque
   
 
   
  Coagulation factors in hemostasis:
  • Understand amplification and feedback mechanisms in coagulation factor cascades
  • Develop replacement and gene therapies for hemophilia A and B and von Willebrand disease
  
      Space filling model of Factor IX
   
 
   
  Platelets for amplification of coagulation:
  • Basic mechanisms of signaling in platelet activation involving Ca2+ channels, small G-proteins and cytoskeletal architecture
  • Lyophilized platelets for the treatment of specific bleeding disorders such as coagulopathies related to hemorrhagic shock
  • Understand the coordinated function of red blood cells as oxygen carriers and platelets as hemostatic agents
 
      Platelets and red blood cells in the microcirculation
   

 
Background
 
The FOBRL was founded by Dr. Kenneth M. Brinkhous in 1960. It is located on 5 acres of land 4 miles from the main UNC campus. In addition to the animal care facility, the FOBRL has approximately 2000 square feet of laboratory space. A staff that includes a Director, Associate Director, research professionals, postdoctoral fellows, students, and professional animal care personnel runs the FOBRL. The FOBRL is the only facility in the world with the long standing genetically-characterized dog and hog population required for studies of clotting factors VIII and IX as well as von Willebrand factor. The facility is AAALAC and USDA approved and meets all federal and state regulations.
 
 
FOBRL Research Programs
 

Hemostasis:

The focus of our hemostasis research is on understanding the pathophysiology of hemophilia A hemophilia B, and von Willebrand disease, and developing improved treatments for these diseases. The FOBRL is endowed with unique assets of priceless animal models of these human diseases, experienced investigators and a well-trained support staff that has a long experience in maintaining and conducting independent and collaborative investigations with these bleeder dogs. This work includes collaborative gene therapy and protein replacement studies. A Resource Grant from the NIH/NHLBI provides the mechanism of support for the maintenance of the colony and production of these animals. Animals entered into investigational studies are supported by those studies. Inquiries about collaborative investigations should contact Dr. Timothy C. Nichols (see contact information at the end of this section).

A second area of focus of our hemostasis research is directed towards production and characterization of rehydratable lyophilized platelets and platelet substitutes for use in transfusion medicine. The same technology is being used to develop and characterization rehydratable lyophilized red blood cells. The goal of this work is to provide long-term stored blood products in the dried state. This work is lead by Dr. Thomas Fischer.
 
Atherosclerosis and Thrombosis:
The focus of our vascular biology research is on the role of von Willebrand factor in thrombosis and atherosclerosis. This work utilizes porcine models of von Willebrand disease and atherosclerosis. Our laboratory is currently working on the molecular biology of porcine von Willebrand factor, the role of shear in the control of vWF production, the influence of atherosclerosis on vWF content in the vessel wall. A new direction in our vascular biology research is on the role of activation of the transcription factor NF-kappaB in the atherosclerotic plaque. This research addresses the recent epidemiological association of oral inflammation and atherogenesis and is being done by Drs. Timothy C. Nichols, Al Baldwin in the Lineberger Comprehensive Cancer Center and the Center for Inflammatory Diseases, and Dwight Bellinger in the Division of Laboratory Animal Medicine. A second new area of research is a focus on diabetic cardiovascular disease performed by Drs. Timothy C. Nichols, Dwight Bellinger, and Dr. David Clemmons, Chief, Endocrinology, Department of Medicine, UNC. The overall objective is to develop a useful, relevant, available porcine model of insulin resistance and atherosclerosis that can be used to identify mechanisms that lead to accelerated atherosclerosis in insulin-resistant humans and to develop and test potential new treatment strategies.
 
Training:
The FOBRL has major teaching and training responsibilities that include undergraduate and graduate school students. An NIH training grant, the American Heart Association Summer Program, and a Minority Training Program have provided support for these educational efforts. Research Residencies in Pathology are available for physicians considering a career in academic medicine.
 
Administration:
The FOBRL is administered through the Department of Pathology and Laboratory Medicine.
 
 
Contact
 
For further information or enrollment, please contact:
 
Dr. Timothy C. Nichols (Director)
Professor of Medicine and of Pathology and Laboratory Medicine
FOBRL, CB# 3114, UNC-CH
Chapel Hill, NC 27599
Phone: 919-966-3274
tnichols@med.unc.edu
 
Dr. Thomas H. Fischer (Scientific Director)
Associate Professor of Pathology and Laboratory Medicine
FOBRL, CB# 3114, UNC-CH
Chapel Hill, NC 27599
Phone: 919-966-3274
tfischer@med.unc.edu
 
 
 
Department of Pathology