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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center


Geraldine G. Miller, M.D.

Professor of Medicine (Infectious Diseases), Emerita
Associate Professor of Microbiology & Immunology

Contact Information:

Vanderbilt University Medical Center
A-3310 Medical Center North
Nashville, TN 37232-2605

  • M.D. - University of California San Diego, 1973
  • Fellowship - National Institutes of Health
  • Internship - University Hospital
  • Post Graduate Training - Beth Israel Deaconess Medical Center
  • Post Graduate Training - National Institute of Allergy and Infectious Diseases of the National Institutes of Health
  • Post Graduate Training - National Institutes of Health Clinical Center
  • Post Graduate Training - University of California San Diego Medical Center
  • Residency - Beth Israel Deaconess Medical Center
Research Specialty

Transplantation and autoimmunity

Research Description

Our research interests are in the regulation of fibroblast growth factor-1 and its receptor FGF receptor 1. Our efforts are focused on improving the outcome of solid organ transplantation by understanding the mechanisms that lead to late graft failure which include dysregulation of FGF and FGF receptor expression.The leading cause of late transplant failure is chronic rejection, manifested in the transplanted heart as severe, accelerated coronary artery disease. Our studies have revealed that fibroblast growth factors and their receptors play an important role in the pathogenesis of these vascular lesions. Cytokines and mediators produced during chronic rejection induce overexpression of FGF in the transplant and additionally cause changes in alternative mRNA splicing of FGF receptors that result in overproduction of active isoforms of the FGF receptor tyrosine kinase. The combination of increased FGF ligand and overexpressed receptor induces exuberant proliferation of smooth muscle cells that line the coronary arteries producing obstructive lesions that lead to ischemia of the cardiac muscle and ultimately to graft failure.

Another site of dysregulated FGF production is in the joints of patients with rheumatoid arthritis. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that results from excessive proliferation of the synovial lining of the joints causing damage to cartilage, erosion of bone, and ultimately joint destruction. The synovial lesions are characterized by extensive infiltration of T cells, neoangiogenesis, and fibroblast proliferation. The latter events are characteristic of effects induced by FGF and indeed FGF and its receptor are dramatically overexpressed in rheumatoid synovial lining compared with normals. Our studies of T cells from RA patients have shown that they include a population responsive to FGF, suggesting that the FGF-rich environment of the rheumatoid joint provides chronic stimulation for such T cells and that they may contribute to the ongoing immune inflammation in the joints.

To understand the effects of FGF dysregulation in these local environments, we have produced transgenic mice that selectively overexpress FGF in T cells. Analysis of the function of these transgenic T cells shows that they have abnormal production of cytokines that may contribute to their persistent activation and the chronic inflammatory responses of rejection and joint inflammation. .