.

Department of Pathology, Microbiology, and Immunology

 

 

  Geraldine G. Miller, M.D.

 

 

Professor

Dept of Medicine

Associate Professor

Dept  of Pathology, Microbiology and Immunology

 

 

Contact Information

 

 

Office Location: 
A-3310 MCN

Phone: 615-322-2035

E-mail:  Geraldine.Miller@vanderbilt.edu

 

Campus Mail address:

Dept of Medicine

A-2200 MCN (2582)

 

US Mailing Address:
Vanderbilt University School of Medicine

Department of Medicine

A-2200 MCN
Nashville, TN 37232-2582

 

 

 

Education

 

 

M.D., California, San Diego
B.S., Massachusetts Institute of Technology

 

 

Research Keywords

 

 


 

 

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. .

 

 

Publications

 

 

Luckett, K, Dummer, JS, Miller, G, Hester, S, Thomas, L. Histoplasmosis in Patients With Cell-Mediated Immunodeficiency: Human Immunodeficiency Virus Infection, Organ Transplantation, and Tumor Necrosis Factor-?? Inhibition. Open Forum Infect Dis, 2(1), ofu116, 2015

Noto, MJ, Koethe, JR, Miller, G, Wright, PW. Detectable serum tobramycin levels in patients with renal dysfunction and recent placement of antibiotic-impregnated cement knee or hip spacers. Clin Infect Dis, 58(12), 1783-4, 2014

Menge, TJ, Koethe, JR, Jenkins, CA, Wright, PW, Shinar, AA, Miller, GG, Holt, GE. Acute kidney injury after placement of an antibiotic-impregnated cement spacer during revision total knee arthroplasty. J Arthroplasty, 27(6), 1221-7.e1-2, 2012

Self, WH, Speroff, T, McNaughton, CD, Wright, PW, Miller, G, Johnson, JG, Daniels, TL, Talbot, TR. Blood culture collection through peripheral intravenous catheters increases the risk of specimen contamination among adult emergency department patients. Infect Control Hosp Epidemiol, 33(5), 524-6, 2012

van der Heijden, YF, Miller, G, Wright, PW, Shepherd, BE, Daniels, TL, Talbot, TR. Clinical impact of blood cultures contaminated with coagulase-negative staphylococci at an academic medical center. Infect Control Hosp Epidemiol, 32(6), 623-5, 2011

Algood, HM, Allen, SS, Washington, MK, Peek, RM, Miller, GG, Cover, TL. Regulation of gastric B cell recruitment is dependent on IL-17 receptor A signaling in a model of chronic bacterial infection. J Immunol, 183(9), 5837-46, 2009

Thomas, LD, Milstone, AP, Miller, GG, Loyd, JE, Stephen Dummer, J. Long-term outcomes of cytomegalovirus infection and disease after lung or heart-lung transplantation with a delayed ganciclovir regimen. Clin Transplant, 23(4), 476-83, 2009

Lawson, WE, Crossno, PF, Polosukhin, VV, Roldan, J, Cheng, DS, Lane, KB, Blackwell, TR, Xu, C, Markin, C, Ware, LB, Miller, GG, Loyd, JE, Blackwell, TS. Endoplasmic reticulum stress in alveolar epithelial cells is prominent in IPF: association with altered surfactant protein processing and herpesvirus infection. Am J Physiol Lung Cell Mol Physiol, 294(6), L1119-26, 2008

Lundquist, AL, Chari, RS, Wood, JH, Miller, GG, Schaefer, HM, Raiford, DS, Wright, KJ, Gorden, DL. Serum sickness following rabbit antithymocyte-globulin induction in a liver transplant recipient: case report and literature review. Liver Transpl, 13(5), 647-50, 2007

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

Khulordava, I, Miller, G, Haas, D, Li, H, McKinsey, J, Vanderende, D, Tang, YW. Identification of the bacterial etiology of culture-negative endocarditis by amplification and sequencing of a small ribosomal RNA gene. Diagn Microbiol Infect Dis, 46(1), 9-11, 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

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

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, 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

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, 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

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

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

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

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

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

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

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, 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

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

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

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., 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

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

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

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, 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

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

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

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

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, 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, 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

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

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

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

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

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

Miller, G G, Strittmatter, W J. Identification of human T cells that require zinc for growth.. Scand J Immunol, 36(2), 269-77, 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

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

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

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