Geraldine G. Miller, M.D.
Professor of Medicine (Infectious Diseases)
Associate Professor of Microbiology & Immunology
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
Transplantation and autoimmunity
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. .
- Miller, GG, Boivin, G, Dummer, JS, McConnell, T, Becher, MW, Kassim, A, Tang, YW Cytomegalovirus ventriculoencephalitis in a peripheral blood stem cell transplant recipient. Clin Infect Dis, 42(4), e26-9, 2006.
- Miller, GG, Destarac, L, Zeevi, A, Girnita, A, McCurry, K, Iacono, A, Murray, JJ, Crowe, D, Johnson, JE, Ninan, M, Milstone, AP Acute humoral rejection of human lung allografts and elevation of C4d in bronchoalveolar lavage fluid. Am J Transplant, 4(8), 1323-30, 2004.
- Crowe, James E, Sannella, Edith C, Pfeiffer, Steffen, Zorn, George L, Azimzadeh, Agnes, Newman, Roland, Miller, Geraldine G, Pierson, Richard N CD154 regulates primate humoral immunity to influenza.. Am J Transplant, 3(6), 680-8, 2003.
- Byrd, Victor M, Kilkenny, Dawn M, Dikov, Michael M, Reich, Martha B, Rocheleau, Jonathan V, Armistead, Wade J, Thomas, James W, Miller, Geraldine G Fibroblast growth factor receptor-1 interacts with the T-cell receptor signalling pathway. Immunol Cell Biol, 81(6), 440-50, 2003.
- Kilkenny, Dawn M, Rocheleau, Jonathan V, Price, James, Reich, Martha B, Miller, Geraldine G c-Src regulation of fibroblast growth factor-induced proliferation in murine embryonic fibroblasts.. J Biol Chem, 278(19), 17448-54, 2003.
- Takeuchi, Hiroaki, Israel, Dawn A, Miller, Geraldine G, Donahue, John P, Krishna, Uma, Gaus, Kristin, Peek, Richard M Characterization of expression of a functionally conserved Helicobacter pylori methyltransferase-encoding gene within inflamed mucosa and during in vitro growth.. J Infect Dis, 186(8), 1186-9, 2002.
- Zhao, David Xiao-Ming, Hu, Yenya, Miller, Geraldine G, Luster, Andrew D, Mitchell, Richard N, Libby, Peter Differential expression of the IFN-gamma-inducible CXCR3-binding chemokines, IFN-inducible protein 10, monokine induced by IFN, and IFN-inducible T cell alpha chemoattractant in human cardiac allografts: association with cardiac allograft vasculopathy and acute rejection.. J Immunol, 169(3), 1556-60, 2002.
- Xu, Qing, Morgan, R D, Roberts, R J, Xu, S Y, van Doorn, L J, Donahue, J P, Miller, G G, Blaser, Martin J Functional analysis of iceA1, a CATG-recognizing restriction endonuclease gene in Helicobacter pylori.. Nucleic Acids Res, 30(17), 3839-47, 2002.
- Donahue, John P, Israel, Dawn A, Torres, Victor J, Necheva, Antoaneta S, Miller, Geraldine G Inactivation of a Helicobacter pylori DNA methyltransferase alters dnaK operon expression following host-cell adherence.. FEMS Microbiol Lett, 208(2), 295-301, 2002.
- Pierson, Richard N, Loyd, James E, Goodwin, Andrea, Majors, Dan, Dummer, J Stephen, Mohacsi, Paul, Wheeler, Alistair, Bovin, Nicolai, Miller, Geraldine G, Olson, Sandy, Johnson, Joyce, Rieben, Robert, Azimzadeh, Agnes Successful management of an ABO-mismatched lung allograft using antigen-specific immunoadsorption, complement inhibition, and immunomodulatory therapy.. Transplantation, 74(1), 79-84, 2002.
- Zhao, X M, Hu, Y, Miller, G G, Mitchell, R N, Libby, P Association of thrombospondin-1 and cardiac allograft vasculopathy in human cardiac allografts.. Circulation, 103(4), 525-31, 2001.
- Pierson, R N, Crowe, J E, Pfeiffer, S, Atkinson, J, Azimzadeh, A, Miller, G G CD40-ligand in primate cardiac allograft and viral immunity.. Immunol Res, 23(2-3), 253-62, 2001.
- Thomas, J W, Thieu, T H, Byrd, V M, Miller, G G Acidic fibroblast growth factor in synovial cells.. Arthritis Rheum, 43(10), 2152-9, 2000.
- Donahue, J P, Peek, R M, Van Doorn, L J, Thompson, S A, Xu, Q, Blaser, M J, Miller, G G Analysis of iceA1 transcription in Helicobacter pylori.. Helicobacter, 5(1), 1-12, 2000.
- Figueiredo, C, Quint, W G, Sanna, R, Sablon, E, Donahue, J P, Xu, Q, Miller, G G, Peek, R M, Blaser, M J, van Doorn, L J Genetic organization and heterogeneity of the iceA locus of Helicobacter pylori.. Gene, 246(1-2), 59-68, 2000.
- Donahue, J P, Israel, D A, Peek, R M, Blaser, M J, Miller, G G Overcoming the restriction barrier to plasmid transformation of Helicobacter pylori.. Mol Microbiol, 37(5), 1066-74, 2000.
- Peek, R M, van Doorn, L J, Donahue, J P, Tham, K T, Figueiredo, C, Blaser, M J, Miller, G G Quantitative detection of Helicobacter pylori gene expression in vivo and relationship to gastric pathology.. Infect Immun, 68(10), 5488-95, 2000.
- Byrd, V M, Ballard, D W, Miller, G G, Thomas, J W Fibroblast growth factor-1 (FGF-1) enhances IL-2 production and nuclear translocation of NF-kappaB in FGF receptor-bearing Jurkat T cells.. J Immunol, 162(10), 5853-9, 1999.
- Miller, G G, Davis, S F, Atkinson, J B, Chomsky, D B, Pedroso, P, Reddy, V S, Drinkwater, D C, Zhao, X M, Pierson, R N Longitudinal analysis of fibroblast growth factor expression after transplantation and association with severity of cardiac allograft vasculopathy.. Circulation, 100(24), 2396-9, 1999.
- Pierson, R N, Chang, A C, Blum, M G, Blair, K S, Scott, M A, Atkinson, J B, Collins, B J, Zhang, J P, Thomas, D W, Burkly, L C, Miller, G G Prolongation of primate cardiac allograft survival by treatment with ANTI-CD40 ligand (CD154) antibody.. Transplantation, 68(11), 1800-5, 1999.
- Chang, A C, Blum, M G, Blair, K S, Scott, M A, Brock, J E, Thomas, D W, Burkly, L C, Miller, G G, Pierson, R N Prolonged anti-CD40 ligand therapy improves primate cardiac allograft survival.. Transplant Proc, 31(1-2), 95, 1999.
- Dikov, M M, Reich, M B, Dworkin, L, Thomas, J W, Miller, G G A functional fibroblast growth factor-1 immunoglobulin fusion protein.. J Biol Chem, 273(25), 15811-7, 1998.
- Peek, R M, Thompson, S A, Donahue, J P, Tham, K T, Atherton, J C, Blaser, M J, Miller, G G Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome.. Proc Assoc Am Physicians, 110(6), 531-44, 1998.
- Peek, R M, Moss, S F, Tham, K T, PÃ©rez-PÃ©rez, G I, Wang, S, Miller, G G, Atherton, J C, Holt, P R, Blaser, M J Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation from apoptosis.. J Natl Cancer Inst, 89(12), 863-8, 1997.
- Sharma, S A, Miller, G G, Peek, R A, PÃ©rez-PÃ©rez, G, Blaser, M J T-cell, antibody, and cytokine responses to homologs of the 60-kilodalton heat shock protein in Helicobacter pylori infection.. Clin Diagn Lab Immunol, 4(4), 440-6, 1997.
- Xu, Q, Peek, R M, Miller, G G, Blaser, M J The Helicobacter pylori genome is modified at CATG by the product of hpyIM.. J Bacteriol, 179(21), 6807-15, 1997.
- Chapman, A, Stewart, S J, Nepom, G T, Green, W F, Crowe, D, Thomas, J W, Miller, G G CD11b+CD28-CD4+ human T cells: activation requirements and association with HLA-DR alleles.. J Immunol, 157(11), 4771-80, 1996.
- Byrd, V, Zhao, X M, McKeehan, W L, Miller, G G, Thomas, J W Expression and functional expansion of fibroblast growth factor receptor T cells in rheumatoid synovium and peripheral blood of patients with rheumatoid arthritis.. Arthritis Rheum, 39(6), 914-22, 1996.
- Zhao, X M, Citrin, B S, Miller, G G, Frist, W H, Merrill, W H, Fischell, T A, Atkinson, J B, Yeoh, T K Association of acidic fibroblast growth factor and untreated low grade rejection with cardiac allograft vasculopathy.. Transplantation, 59(7), 1005-10, 1995.
- Zhao, X M, Frist, W H, Yeoh, T K, Miller, G G Confirmation of alternatively spliced platelet-derived growth factor-A chain and correlation with expression of PDGF receptor-alpha in human cardiac allografts.. Transplantation, 59(4), 605-11, 1995.
- Zhao, X-M., Byrd, V.M., McKeehan, W.L., Reich, M.B., Miller, G.G., and Thomas, J.W "Costimulation of CD4+ T cells by fibroblast growth factor-1." J. Immunol., 1553904-3911, 1995.
- Zhao, X M, Byrd, V M, McKeehan, W L, Reich, M B, Miller, G G, Thomas, J W Costimulation of human CD4+ T cells by fibroblast growth factor-1 (acidic fibroblast growth factor).. J Immunol, 155(8), 3904-11, 1995.
- Peek, R M, Miller, G G, Tham, K T, PÃ©rez-PÃ©rez, G I, Cover, T L, Atherton, J C, Dunn, G D, Blaser, M J Detection of Helicobacter pylori gene expression in human gastric mucosa.. J Clin Microbiol, 33(1), 28-32, 1995.
- Miller, G G, Blair, G K Determining risk of surgical-site infections.. CMAJ, 152(9), 1381-2, 1995.
- Peek, R M, Miller, G G, Tham, K T, Perez-Perez, G I, Zhao, X, Atherton, J C, Blaser, M J Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains.. Lab Invest, 73(6), 760-70, 1995.
- Sharma, S A, Tummuru, M K, Miller, G G, Blaser, M J Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro.. Infect Immun, 63(5), 1681-87, 1995.
- Byrd, V M, Zhao, X M, Miller, G G, Thomas, J W Detection of T cells responsive to a vascular growth factor in rheumatoid arthritis.. Immunol Res, 13(2-3), 139-44, 1994.
- Sharma, S A, Miller, G G, Perez-Perez, G I, Gupta, R S, Blaser, M J Humoral and cellular immune recognition of Helicobacter pylori proteins are not concordant.. Clin Exp Immunol, 97(1), 126-32, 1994.
- Zhao, X-M, Yeoh, T-K, Frist, W.H., and Miller, G.G "Induction of acidic fibroblast growth factor (FGF) and full length platelet-derived growth factor (PDGF) expression in human cardiac allografts." Circulation , 90677-685, 1994.
- Zhao, X M, Yeoh, T K, Frist, W H, Porterfield, D L, Miller, G G Induction of acidic fibroblast growth factor and full-length platelet-derived growth factor expression in human cardiac allografts. Analysis by PCR, in situ hybridization, and immunohistochemistry.. Circulation, 90(2), 677-85, 1994.
- Zhao, X-M, Yeoh, T-K, Frist, W.H., and Miller, G.G "Modification of alternative mRNA splicing in human cardiac allografts during rejection." J. Clin. Invest., 94992-1003, 1994.
- Zhao, X M, Frist, W H, Yeoh, T K, Miller, G G Modification of alternative messenger RNA splicing of fibroblast growth factor receptors in human cardiac allografts during rejection.. J Clin Invest, 94(3), 992-1003, 1994.
- Mollick, J A, Miller, G G, Musser, J M, Cook, R G, Grossman, D, Rich, R R A novel superantigen isolated from pathogenic strains of Streptococcus pyogenes with aminoterminal homology to staphylococcal enterotoxins B and C.. J Clin Invest, 92(2), 710-9, 1993.
- Zhao, X M, Frist, W H, Yeoh, T K, Miller, G G Expression of cytokine genes in human cardiac allografts: correlation of IL-6 and transforming growth factor-beta (TGF-beta) with histological rejection.. Clin Exp Immunol, 93(3), 448-51, 1993.
- Zhao, X M, Yeoh, T K, Hiebert, M, Frist, W H, Miller, G G The expression of acidic fibroblast growth factor (heparin-binding growth factor-1) and cytokine genes in human cardiac allografts and T cells.. Transplantation, 56(5), 1177-82, 1993.
- Miller, G G, Strittmatter, W J Identification of human T cells that require zinc for growth.. Scand J Immunol, 36(2), 269-77, 1992.
- Mollick, J A, Miller, G G, Musser, J M, Cook, R G, Rich, R R Isolation and characterization of a novel streptococcal superantigen.. Trans Assoc Am Physicians, 105110-22, 1992.
- Ulrich, R G, Thomas, J W, Miller, G G, Atassi, M Z DR beta peptides block the antigen-specific response but not the alloresponse of a dual-reactive T-cell clone.. Immunol Lett, 24(1), 43-7, 1990.
- Miller, G G, Hoy, J F, Thomas, J W Insulin B chain functions as an effective competitor of antigen presentation via peptide homologies present in the thymus.. J Exp Med, 169(6), 2251-6, 1989.
- Hoy, J F, Murphy, J W, Miller, G G T cell response to soluble cryptococcal antigens after recovery from cryptococcal infection.. J Infect Dis, 159(1), 116-9, 1989.
- Miller, G G, Hoy, J F, Nell, L J, Thomas, J W Antigen processing and the human T cell receptor repertoire for insulin.. J Immunol, 141(10), 3293-8, 1988.
- Hoy, J F, Lewis, D E, Miller, G G Functional versus phenotypic analysis of T cells in subjects seropositive for the human immunodeficiency virus: a prospective study of in vitro responses to Cryptococcus neoformans.. J Infect Dis, 158(5), 1071-8, 1988.
- Miller, G G, Pollack, M S, Nell, L J, Thomas, J W Insulin-specific human T cells. Epitope specificity, major histocompatibility complex restriction, and alloreactivity to a diabetes-associated haplotype.. J Immunol, 139(11), 3622-9, 1987.
- Devaux, C A, Nadler, P I, Miller, G G, Sachs, D H Genetic control of immune response to staphylococcal nuclease. XII: Analysis of nuclease antigenic determinants using anti-nuclease monoclonal antibodies.. Mol Cell Biochem, 68(1), 31-40, 1985.
- Miller, G G, Nadler, P I, Hodes, R J, Sachs, D H Modification of T cell antinuclease idiotype expression by in vivo administration of anti-idiotype.. J Exp Med, 155(1), 190-200, 1982.
- Nadler, P I, Miller, G G, Sachs, D H, Hodes, R J The expression and functional involvement of nuclease- specific idiotype on nuclease-primed helper T cells.. Eur J Immunol, 12(2), 113-20, 1982.