Marguerite Jones Harbert - Gene V. Ball, MD
Professor of Medicine
Director, Division of Clinical Immunology & Rheumatology
Shelby Building, Room 178C
1825 University Boulevard
Telephone: (205) 934-7000
Administrative Associate: Paula Kiley
Shelby Building, Room 178A
1825 University Blvd.
BS, Preprofessional Studies, University of Notre Dame, 1980
MD, Louisiana State Univerisity School of Medicine, 1984
PhD, University of Alabama at Birmingham, 1995
Internship and Residency, Internal Medicine, University of Texas Medical Branch, Galveston 1984-1987
Chief Residency, Internal Medicine, University of Texas Medical Branch, Galveston 1987-1988
Fellowship, Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 1988-1991
|Stephanie S. Ledbetter, MS
|Zenoria L. Causey, MPH
|Yuanqing Z. Edberg
|Selena D. Luckett-Smith, RN
|Laticia Woodruff, RN
|Ashutosh Tamhane, MD, MSPH
Click here to meet some of the staff in Dr. Bridges lab
Research Description and Potential Projects for Trainees
Our research program is focused on identification of genetic and non-genetic influences on rheumatoid arthritis susceptibility, severity, and treatment response, as delineated below.
Genetic and non-genetic influences on RA susceptibility and severity in African-Americans. Through the Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) Registry (NIH N01-AR-6-2278 - SL Bridges, Jr., PI), we are collecting clinical information and biological samples from African-Americans with RA. The current goals of CLEAR Registry are: 1) to complete our ongoing longitudinal evaluation of 400 African-Americans with early rheumatoid arthritis and enrollment of 200 healthy African-American controls matched for age-, sex-, and geographic location; and 2) to compile extensive demographic, socioeconomic, clinical, and radiographic data on 600 additional African-Americans with longstanding RA and 300 additional healthy African-American controls matched for age-, sex-, and geographic location. When complete, the CLEAR Registry will provide comprehensive clinical, socioeconomic, and radiographic data, as well as DNA, RNA, and serum on 1,000 patients and 500 controls for the scientific community.
We have a research project that is part of UAB's NIH-funded Multidisciplinary Clinical Research Center Project (2P60 AR048095 - Robert P. Kimberly, PI). This project, Predictors of Rheumatoid Arthritis Severity in African-Americans (SL Bridges, Jr., PI), has the following goals: 1) To identify differences in baseline gene expression profiles between African-American patients with RA and severe radiographic damage and those with no radiographic damage at 3 years' disease duration; 2) To identify differences in baseline serologic factors between African-American patients with RA and severe radiographic damage and those with no radiographic damage at 3 years' disease duration; and 3) To determine the relative contributions of baseline clinical, genetic, serologic, socioeconomic, environmental factors, and treatment on radiographic severity of RA in African-Americans at 3 years' disease duration.
In collaboration with investigators at the HudsonAlpha Institute of Biotechnology in Huntsville, Alabama, we will search for new genetic loci associated with RA in African-Americans through the project Genome-Wide Association Study in African-Americans with Rheumatoid Arthritis (NIH R01 AR057202-01 - SL Bridges, Jr., PI). The goals of this project are:; 1) to perform a genome-wide association study (GWAS) in 800 African-Americans with anti-CCP antibody positive RA and 800 controls to identify novel genetic associations; 2) to replicate these putative associations for susceptibility to CCP+ RA among African-Americans in independent set of 800 African-American CCP+ RA patients and 800 matched controls (which will be constituted by establishing the African-American Rheumatoid Arthritis Network (AARAN) and 3) To further characterize genetic regions associated with RA in African-Americans and to analyze genome-wide associations with radiographic severity; bone mineral density in early RA and healthy controls; and expression quantitative trait loci (eQTLs) of genes expressed in peripheral blood mononuclear cells, particularly those associated with radiographic severity.
Predictors of Response to Treatment in Rheumatoid Arthritis. As part of UAB's NIH-funded Multidisciplinary Clinical Research Center Project (see above), we have a project in collaboration with Drs. Donna Arnett and Beth Brown in the UAB Department of Epidemiology. This project, Genetic and Molecular Markers of Methotrexate Efficacy and Toxicity in Early RA (DK Arnett, PI), has the following goals: 1) To characterize the association between genetic variation and MTX efficacy, toxicity, and polyglutamate concentrations in early aggressive RA by genotyping haplotype-tagging SNPs or genetic variants reported to be related to methotrexate (MTX) efficacy, toxicity, and/or polyglutamination of MTX in 26 candidate genes in patients in the TEAR Trial (see below) 2) To conduct sophisticated analyses of single variants and haplotypes to assess the association between genetic variation and (a) efficacy (the longitudinal change in the DAS28 score from baseline to 24 weeks; (b) MTX polyglutamate concentrations measured using HPLC (high performance liquid chromatography), and (c) MTX toxicity during the first 24 weeks of the trial; and 3) To evaluate the role of non-genetic factors that mediate the effect of the genetic variants identified in Aim1 to influence efficacy, polyglutamate concentration, and toxicity.
The studies outlined in the project Genetic and Molecular Markers of Methotrexate Efficacy and Toxicity in Early RA are based on the Treatment of Early Aggressive Arthritis (TEAR) Trial led by Dr. Larry Moreland (now at the University of Pittsburgh) and Drs. Jeff Curtis, Stacey Cofield, and George Howard. The primary objective of this proposal is to evaluate the relative efficacy of two clinically important decisions as measured by the average DAS28 and two years after initiation of treatment: 1) To assess if it is better to intensively treat all early RA patients with multiple DMARDs, or reserve this treatment only to those who do not appropriately respond to MTX monotherapy and 2) To assess if the combination therapy of MTX plus etanercept is superior to MTX plus sulfasalazine plus hydroxychloroquine. Biological samples (DNA, RNA, serum/plasma) from patients enrolled in the TEAR Trial were collected as part of NIH R01 AR052658 (Predictors of Treatment Response in Early Aggressive RA - SL Bridges, Jr., PI), which ended in 2009.
Through the NIH Grand Opportunity grant Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository (TETRAD) (NIH 1 RC2 AR058964 - SL Bridges, Jr., PI), we will pursue the following goals: 1) to create a collaborative network of leading academic investigators that will harmonize efforts to collect treatment response data and biologic samples in RA patients starting methotrexate (MTX) or biologic agents; 2) to implement a protocol recently constructed by leading academic rheumatologists, biostatisticians, geneticists, and immunologists to facilitate uniform data and specimen collection from RA patients starting treatment; 3) a. To perform a "proof of concept" study to determine the feasibility of this infrastructure by enrolling a small number of RA patients (10/year/site) beginning therapy;; 3) b. to utilize financial and in-kind contributions from the Arthritis Foundation and corporate partners to perform pilot projects to facilitate additional grant funding on mechanisms of treatment response in RA; and 4) to leverage the successes garnered in Aims 1-3 to stimulate collaborative efforts of federal funding agencies, voluntary health agencies, professional organizations and industry partners to enable creation of a large, sustainable database and repository to better understand the molecular basis of treatment and rapidly accelerate translational research in RA.
Umicevic Mirkov M, Cui J, Vermeulen SH, Stahl EA, Toonen EJ, Makkinje RR, Lee AT, Huizinga TW, Allaart R, Barton A, Mariette X, Miceli CR, Criswell LA, Tak PP, de Vries N, Saevarsdottir S, Padyukov L, Bridges SL, van Schaardenburg DJ, Jansen TL, Dutmer EA, van de Laar MA, Barrera P, Radstake TR, van Riel PL, Scheffer H, Franke B, Brunner HG, Plenge RM, Gregersen PK, Guchelaar HJ, Coenen MJ. 2012. Genome-wide association analysis of anti-TNF drug response in patients with rheumatoid arthritis. Ann Rheum Dis. 2012 Dec 11. [Epub ahead of print] PMID:23233654
Halilova KI, Brown EE, Morgan SL, Bridges SL Jr, Hwang MH, Arnett DK, Danila MI. 2012. Markers of treatment response to methotrexate in rheumatoid arthritis: where do we stand? Int J Rheumatol. 2012:978396. PMID:22844292
Moreland LW, O'Dell JR, Paulus HE, Curtis JR, Bathon JM, St Clair EW, Bridges SL Jr, Zhang J, McVie T, Howard G, van der Heijde D, Cofield SS; TEAR Investigators. 2012. A randomized comparative effectiveness study of oral triple therapy versus etanercept plus methotrexate in early aggressive rheumatoid arthritis: the treatment of early aggressive rheumatoid arthritis trial. Arthritis Rheum. 64(9):2824-35. PMID:22508468
Singh JA, Furst DE, Bharat A, Curtis JR, Kavanaugh AF, Kremer JM, Moreland LW, O'Dell J, Winthrop KL, Beukelman T, Bridges SL Jr, Chatham WW, Paulus HE, Suarez-Almazor M, Bombardier C, Dougados M, Khanna D, King CM, Leong AL, Matteson EL, Schousboe JT, Moynihan E, Kolba KS, Jain A, Volkmann ER, Agrawal H, Bae S, Mudano AS, Patkar NM, Saag KG. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 64(5):625-39. PMID:22473917
Kurreeman FA, Stahl EA, Okada Y, Liao K, Diogo D, Raychaudhuri S, Freudenberg J, Kochi Y, Patsopoulos NA, Gupta N; CLEAR investigators, Sandor C, Bang SY, Lee HS, Padyukov L, Suzuki A, Siminovitch K, Worthington J, Gregersen PK, Hughes LB, Reynolds RJ, Bridges SL Jr, Bae SC, Yamamoto K, Plenge RM. 2012. Use of a multiethnic approach to identify rheumatoid- arthritis-susceptibility loci, 1p36 and 17q12. Am J Hum Genet. 90(3):524-32. PMID:22365150
Reynolds RJ, Cui X, Vaughan LK, Redden DT, Causey Z, Perkins E, Shah T, Hughes LB; CLEAR Investigators, Damle A, Kern M, Gregersen PK, Johnson MR, Bridges SL Jr. 2012. Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis. Rheumatol Int. 2012 Jan 12. [Epub ahead of print] PMID:22238028
Perkins EA, Landis D, Causey ZL, Edberg Y, Reynolds RJ, Hughes LB, Gregersen PK, Kimberly RP, Edberg JC, Bridges SL Jr; Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis Investigators. 2012. Association of single-nucleotide polymorphisms in CCR6, TAGAP, and TNFAIP3 with rheumatoid arthritis in African Americans. Arthritis Rheum. 64(5):1355-8. PMID:22127930
Mikuls TR, Levan T, Gould KA, Yu F, Thiele GM, Bynote KK, Conn D, Jonas BL, Callahan LF, Smith E, Brasington R, Moreland LW, Reynolds R, Gaffo A, Bridges SL Jr. 2012. Impact of interactions of cigarette smoking with NAT2 polymorphisms on rheumatoid arthritis risk in African Americans. Arthritis Rheum. 64(3):655-64. PMID:21989592
Song JJ, Hwang I, Cho KH, Garcia MA, Kim AJ, Wang TH, Lindstrom TM, Lee AT, Nishimura T, Zhao L, Morser J, Nesheim M, Goodman SB, Lee DM, Bridges SL Jr; Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry, Gregersen PK, Leung LL, Robinson WH. 2011. Plasma carboxypeptidase B downregulates inflammatory responses in autoimmune arthritis. J Clin Invest. 121(9):3517-27. PMID:21804193
Plenge RM, Bridges SL Jr, Huizinga TW, Criswell LA, Gregersen PK. 2011. Recommendations for publication of genetic association studies in Arthritis & Rheumatism. Arthritis Rheum. 63(10):2839-47. PMID:21702018
Plenge RM, Bridges SL Jr. 2011. Personalized medicine in rheumatoid arthritis: miles to go before we sleep. Arthritis Rheum. 63(3):590-3. doi: 10.1002/art.30126. PMID: 21360486
Hughes LB, Reynolds RJ, Brown EE, Kelley JM, Thomson B, Conn DL, Jonas BL, Westfall AO, Padilla MA, Callahan LF, Smith EA, Brasington RD, Edberg JC, Kimberly RP, Moreland LW, Plenge RM, Bridges SL Jr. 2010. Most common single-nucleotide polymorphisms associated with rheumatoid arthritis in persons of European ancestry confer risk of rheumatoid arthritis in African Americans. Arthritis Rheum. 62(12):3547-53. doi: 10.1002/art.27732. PMID: 21120996
Mikuls TR, Gould KA, Bynoté KK, Yu F, Levan TD, Thiele GM, Michaud KD, O'Dell JR, Reimold AM, Hooker R, Caplan L, Johnson DS, Kerr G, Richards JS, Cannon GW, Criswell LA, Noble JA, Bridges SL Jr, Hughes L, Gregersen PK. 2010. Anticitrullinated protein antibody (ACPA) in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione s-transferase in a cross-sectional study. Arthritis Res Ther. 12(6):R213. PMID: 21087494
Mikuls TR, Sayles H, Yu F, Levan T, Gould KA, Thiele GM, Conn D, Jonas BL, Callahan LF, Smith E, Brasington R, Moreland LW, Reynolds R, Bridges SL Jr. 2010. Associations of cigarette smoking with rheumatoid arthritis in African Americans. Arthritis Rheum. 2010 Aug 18. [Epub ahead of print]. PMID: 20722010
Fessler BJ, Bridges SL Jr. 2010. ANCA-associated vasculitis. Preface. Rheum Dis Clin North Am 36(3):xiii.PMID: 20688241
Curtis JR, Jain A, Askling J, Bridges SL Jr, Carmona L, Dixon W, Finckh A, Hyrich K, Greenberg JD, Kremer J, Listing J, Michaud K, Mikuls T, Shadick N, Solomon DH, Weinblatt ME, Wolfe F, Zink A. 2010. A comparison of patient characteristics and outcomes in selected European and U.S. rheumatoid arthritis registries. Semin Arthritis Rheum. 40(1):2-14.e1. PMID: 20674669
Danila MI, Hughes LB, Brown EE, Morgan SL, Baggott JE, Arnett DK, Bridges SL Jr. 2010. Measurement of erythrocyte methotrexate polyglutamate levels: ready for clinical use in rheumatoid arthritis? Curr Rheumatol Rep 12(5):342-7. PMID: 20665136
Hughes LB, Reynolds RJ, Brown EE, Kelley JM, Thomson B, Conn DL, Jonas BL, Westfall AO, Padilla MA, Callahan LF, Smith EA, Brasington RD Jr., Edberg JC, Kimberly RP, Moreland LW, Plenge RM, Bridges SL Jr. Most common SNPs associated with rheumatoid arthritis in subjects of European ancestry confer risk of rheumatoid arthritis in African-Americans. Arthritis & Rheumatism, accepted for publication.
Tan W, Wu H, Zhao J, Derber LA, Lee DM, Shadick NA, Conn DL, Smith EA, Gersuk VH, Nepom GT, Moreland LW, Furst DE, Thompson SD, Jonas BL, Michael Holers V, Glass DN, Chen PP, Bridges SL Jr, Weinblatt ME, Paulus HE, Tsao BP. A functional RANKL polymorphism associated with younger age at onset of rheumatoid arthritis. Arthritis Rheum. 62(10):2864-75. PMID: 20533289.
Zhang J, Redden DT, McGwin G Jr, Callahan LF, Smith EA, Alarcón GS, Moreland LW, van der Heijde DM, Brown EE, Arnett DK, Mikuls TR, Bridges SL Jr; for the CLEAR Investigators. Generalized bone loss as a predictor of 3-year radiographic damage in African American patients with recent-onset rheumatoid arthritis. Arthritis Rheum. 62(8): 2219-26. PMID: 20506234.
Bridges SL Jr., Causey ZL, Burgos PI, Huynh QN, Hughes LB, Danila MI, van Everdingen A, Ledbetter S, Conn DL, Tamhane A, Westfall AO, Jonas BL, Callahan LF, Smith EA, Brasington R, Moreland LW, Alarcón GS, van der Heijde DM. 2010. Radiographic Severity of Rheumatoid Arthritis in African-Americans: Results from the CLEAR Registry. Arthritis Care & Research, 62(5):624-31. PubMed PMID: 20461784.
Burgos PI, Causey ZL, Tamhane A, Kelley JM, Brown EE, Hughes LB, Danila MI, van Everdingen A, Conn DL, Jonas BL, Callahan LF, Smith EA, Brasington R, Moreland LW, van der Heijde DM, Alarcon GS, Bridges SL Jr. 2010. Association of IL4R single nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis. Arthritis Res Ther. 12(3):R75. PMID: 20444266.
Cui J, Saevarsdottir S, Thomson B, Padyukov L, van der Helm-van Mil AH, Nititham J, Hughes LB, de Vries N, Raychaudhuri S, Alfredsson L, Askling J, Wedrén S, Ding B, Guiducci C, Wolbink GJ, Crusius JB, van der Horst-Bruinsma IE, Herenius M, Weinblatt ME, Shadick NA, Worthington J, Batliwalla F, Kern M, Morgan AW, Wilson AG, Isaacs JD, Hyrich K, Seldin MF, Moreland LW, Behrens TW, Allaart CF, Criswell LA, Huizinga TW, Tak PP, Bridges SL Jr, Toes RE, Barton A, Klareskog L, Gregersen PK, Karlson EW, Plenge RM; 2010. Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy. Arthritis Rheum. 62(7):1849-61. PMID: 20309874.
Curtis JR, Arora T, Donaldson M, Alarcón GS, Callahan LF, Moreland LW, Bridges SL 2009. Skeletal health among African Americans with recent-onset rheumatoid arthritis. Arthritis Rheum. 61(10):1379-86. PMID: 19790118
Reynolds RJ, Kelley JM, Hughes LB, Yi N, Bridges SL Jr. 2009. Genetic association of htSNPs across the major histocompatibility complex with rheumatoid arthritis in an African-American population. Genes Immun. 11(1):94-7. PMID: 19741715
Gregersen PK, Amos CI, Lee AT, Lu Y, Remmers EF, Kastner DL, Seldin MF, Criswell LA, Plenge RM, Holers VM, Mikuls TR, Sokka T, Moreland LW, Bridges SL Jr, Xie G, Begovich AB, Siminovitch KA. 2009. REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. Nat Genet. 41(7):820-3. PMID: 19503088