Biomedical Research Education & Training
Faculty Member

Miller, Geraldine G., M.D.
Professor of Medicine, Emerita
Associate Professor of Pathology, Microbiology and Immunology

Lab Url: N/A

Phone Number: 615-322-2035

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Miller, Geraldine's picture
Academic history
B.S., Massachusetts Institute of Technology
M.D., California, San Diego

Office Address   Mailing Address

A-3310 Medical Center North

A-2200 MCN 2582

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. .

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

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

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

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

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

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

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 PMCID:137426

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

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

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

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

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

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 PMCID:101496

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

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

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

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

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, P??rez-P??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, P??rez-P??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 PMCID:170547

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 PMCID:179612

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

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

Miller, G G, Blair, G K. Determining risk of surgical-site infections.. CMAJ, 152(9), 1381-2, 1995 PMCID:1337899

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

Peek, R M, Miller, G G, Tham, K T, P??rez-P??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 PMCID:227873

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 PMCID:173210

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

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., 155, 3904-3911, 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 PMCID:1534772

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 PMCID:295146

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., 94, 992-1003, 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 , 90, 677-685, 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 PMCID:294905

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 PMCID:1554893

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, 105, 110-22, 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

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, 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 PMCID:2189354

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, 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

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 PMCID:2186558

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

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