V. Michael Holers, MD
Professor, Medicine-Rheumatology

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Medical School:
  • MD, Washington University in St. Louis School of Medicine (1978)
Internship:
  • Washington University/Barnes-Jewish Hospital/St. Louis Children's Hospital (1979)
Residency:
  • Washington University/Barnes-Jewish Hospital/St. Louis Children's Hospital, Internal Medicine (1981)
Fellowships:
  • Washington University/Barnes-Jewish Hospital/St. Louis Children's Hospital, Rheumatology (1985)
  • University of Colorado, Rheumatology (1983)
Languages: English
Department: Medicine-Rheumatology

Professional Titles

  • Head, Division of Rheumatology
  • Scoville Professor of Rheumatology

Recognition & Awards

  • Alumni Achievement Award, Washington University School of Medicine (2018)
  • Riven Lectureship, Vanderbilt University (2018)
  • Master, American College of Rheumatology (2017)
  • Duncan Gordon Manuscript Award, Journal of Rheumatololgy (2017)
  • SCARI Lectureship, University of Arizona (2017)
  • Top 5% Reviewer, Arthritis and Rheumatology (2017)

Research Interests

Dr. Holers is performing basic and translational research on the roles of complement receptors and membrane regulatory proteins in the immune response, with a special emphasis on B lymphocytes and autoimmune diseases. Complement is a complex system of serum proteins which, upon activation, covalently bind targets (bacteria, viruses, immune complexes) and marks them as foreign. The interaction of complement with B cell receptors also results in substantial enhancement of humoral and cellular immunity. In addition to this role, excessive activation of complement is centrally involved in autoimmunity and the tissue damage that occurs in many inflammatory diseases involving organs such as the kidney. The Holers’ laboratory has developed human and mouse models in which to study these complement related biologic processes and develop inhibitors. With regard to the natural history studies of RA, we now know that autoimmune diseases begin years before clinical signs and symptoms are apparent, when at-risk individuals manifest highly predictive autoantibodies in their serum. This observation suggests that additional therapeutic and/or prevention strategies could be considered for individuals in this at-risk but asymptomatic period. It is also relevant to determine how individuals transition from this autoantibody-positive, at-risk period to clinically active disease, and ongoing studies have been started that are related to understanding these questions.

Publications

  • Seifert, J.A., Bemis, E.A., Ramsden, K., Lowell, C., Polinski, K., Fleischer, C., Demoruelle, M.K., Buckner, J., Gregersen, P.K., Keating, R.M., Mikuls, T.R., O’Dell, J.R., Weisman, M.H., Deane, K.D., Norris, J.M., Steere, A.C., and Holers, V.M. 2023. Association of antibodies to Prevotella copri in anti-CCP-positive individuals at-risk for developing rheumatoid arthritis and in those with early or established rheumatoid arthritis. Arth. Rheum. 75:507-516. PMCID: PMC10065886
  • Holers, V.M., Frank, R.M., Clauw, A., Seifert, J., Zuscik, M., Asokan, S., Striebich, C., Clay, M.R., Moreland, L.W., and Banda, N.K. 2023. Potential causal role of synovial complement system activation in the development of post-traumatic osteoarthritis after anterior cruciate ligament injury or meniscus tear. Front. Immunol. 2023 doi: 10.3389/fimmu.2023.1146563. PMCID: PMC10189880
  • Renner, B., Poppelaars, F., Laskowski, J., Serkova, N.J., Kulik, L., Holers, V.M., and Thurman, J.M. 2023. Noninvasive detection of iC3b/C3d deposits in the kidney using a novel bioluminescent imaging probe. J. Am. Soc. Nephrol. 34:1151-1154. PMCID: PMC10356150
  • Brewer, R.C., Lanz, T.V., Hale, C.R., Sepich-Poore, G.D., Martino, C., Swafford, A.D., Carroll, T.S., Kongpachith, S., Blum, L.K., Elliott, S.E., Blachere, N.E., Parveen, S., Fak, J., Yao, V., Troyanskaya, O., Frank, M.O., Bloom, M.S., Jahanbani, S., Gomez, A.M., Iyer, R., Ramadoss, N.S., Sharpe, O., Chandrasekaran, S., Kelmenson, L.B., Wang, Q., Wong, H., Torres, H.L., Wiesen, M., Graves. D.T., Deane, K.D., Holers, V.M., Knight, R., Darnell, R.B., Robinson, W.H., and Orange, D.E. 2023. Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis. Sci. Transl. Med. doi: 10.1126/scitranslmed.abq8476. Epub 2023 Feb 22. PMCID: PMC10496947
  • Moon, J.S., Younis, S., Ramadoss, N.S., Iyer, R., Sheth, K., Sharpe, O., Rao, N.L., Becart. S., Carman, J.A., James, E.A., Buckner, J.H., Deane, K.D., Holers, V.M., Goodman, S.M., Donlin, L.T., Davis, M.M., and Robinson, W.H. 2023. Cytotoxic CD8 T cells target citrullinated antigens in rheumatoid arthritis. Nat. Commun. doi:10.1038/s41467-022-35264-8. PMCID: PMC9852471
  • Sarkar, S., Elliott, E.C., Henry, H.R., Ludovico, I.D., Melchior, J.T., Frazer-Abel, A., Webb-Robertson, B.J., Davidson, W.S., Holers, V.M., Rewers, M.J., Metz, T.O., and Nakayasu, E.S. 2023. Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response. Update in: Clin. Proteomics. 20:38. PMCID: PMC9980237
  • Webb-Robertson, B.M., Nakayasu, E.S., Dong, F., Waugh, K.C., Flores, J., Bramer, L.M., Schepmoes, A., Gao, Y., Fillmore, T., Onengut-Gumuscu, S., Frazer-Abel, A., Rich, S.S., Holers, V.M., Metz, T.O., and Rewers, M.J. 2023. Decrease in multiple complement protein levels is associated with the development of islet autoimmunity and type 1 diabetes. medRxiv Jul 16:2023.07.13.23292628. doi: 10.1101/2023.07.13.23292628. PMCID: PMC10370226
  • Onengut-Gumuscu, S., Webb-Robertson, B.M., Sarkar, S., Manichaikul, A., Hu, X., Frazer-Abel, A., Holers, V.M., Rewers, M.J., and Rich, S.S. 2023. Genetic variants in the complement system and their potential link in the aetiology of type 1 diabetes. Diabetes Metab. Res. Rev. Aug 30:e3716. doi: 10.1002/dmrr.3716. PMID:37649398
  • Whelan, R., Feemster, A., Laskowski, J., Renner, B., Kulik, L., Poppelaars, F., Lee, C., Holers, V.M., and Thurman, J.M. 2023. Female but not male mice deficient in soluble IgM Are susceptible to chemically induced glomerular injury. J. Immunol. 211:1240-1248. PMCID:PMC10592129
  • Weisenfeld, D., Zhang, F., Donlin, L., Jonsson, A.H., Apruzzese, W., Campbell, D.; Accelerating Medicines Partnership Program: RA/SLE Network; Rao, D.A., Wei, K., Holers, V.M., Gravallese, E., Moreland, L., Goodman, S., Brenner, M., Raychaudhuri, S., Filer, A., Anolik, J., Bykerk, V., and Liao, K.P. 2023. Associations between rheumatoid arthritis clinical factors with synovial cell types and states. Arth. Rheum. doi: 10.1002/art.42726. PMID: 37791989
  • Li, ,Y., Jacques, S., Gaikwad, H., Wang, G., Banda, N.K., Holers, V.M., Scheinman, R.I., Tomlinson, S., Moghimi, S.M., and Simberg, D. 2023. Inhibition of acute complement responses towards bolus-injected nanoparticles using targeted short-circulating regulatory proteins. Nat Nanotechnol. doi:10.1038/s41565-023-01514-z. PMID: 37798566
  • Mueller, A.A., Sasaki, T., Keegan, J.W., Nguyen, J.P., Griffith, A., Horisberger, A.M., Licata, T., Fieg, E., Cao, Y., Elahee, M., Marks, K.E., Simmons, D.P., Briere, L.C., Cobban, L.A., Pallais, J.C., High, F.A., Walker, M.A., Linnoila, J.J., Sparks, J.A., Holers, V.M., Costenbader, K.H., Network Udn UD, Sweetser, D.A., Krier, J.B., Loscalzo, J., Lederer, J.A., and Rao, D.A. 2023. High-dimensional immunophenotyping reveals immune cell aberrations in patients with undiagnosed inflammatory and autoimmune diseases. J. Clin. Invest. doi:10.1172/JCI169619. PMID: 37874643
  • Zhang, F., Jonsson, A.H., Nathan, A., Millard, N., Curtis, M., Xiao, Q., Gutierrez-Arcelus, M., Apruzzese, W., Watts, G.F.M., Weisenfeld, D., Nayar, S., Rangel-Moreno, J., Meednu, N., Marks, K.E., Mantel, I., Kang, J.B., Rumker, L., Mears, J., Slowikowski, K., Weinand, K., Orange, D.E., Geraldino-Pardilla, L., Deane, K.D., Tabechian, D., Ceponis, A., Firestein, G.S., Maybury, M., Sahbudin, I., Ben-Artzi, A., Mandelin, A.M., Nerviani, A., Lewis, M.J., Rivellese, F., Pitzalis, C., Hughes, L.B., Horowitz, D., DiCarlo, E., Gravallese, E.M., Boyce, B.F.; Accelerating Medicines Partnership: RA/SLE Network; Moreland, L.W., Goodman, S.M., Perlman, H., Holers, V.M., Liao, K.P., Filer, A., Bykerk, V.P., Wei, K., Rao, D.A., Donlin, L.T., Anolik, J.H., Brenner, M.B., and Raychaudhuri, S. 2023. Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes. Nature. 623:616-624. PMCID: PMC10651487
  • James, E.A.*, Holers, V.M.*, Iyer, R., Prideaux, E.B., Rao, N.L., Rims, C., Muir, V.S., Posso, S.E., Bloom, M.S., Zia, A., Elliott, S.E., Adamska, J.Z., Ai, R., Brewer, R.C., Seifert, J.A., Moss, L., Barzideh, S., Demoruelle, M.K., Striebich, C.C., Okamoto, Y., Sainbayar, E., Crook, A.A., Peterson, R.A., Vanderlinden, L.A., Wang, W., Boyle, D.L., Robinson, W.H., Buckner, J.H., Firestein, G.S., and Deane, K.D. 2023. Multifaceted immune dysregulation characterizes individuals at-risk for rheumatoid arthritis. Nat. Commun. doi:10.1038/s41467-023-43091-8. *Co-first author. PMCID: PMC10665556
  • Holers, V.M. 2023. Contributions of animal models to mechanistic understandings of antibody-dependent disease and roles of the amplification loop. Immunol. Rev. 313:181-193. PMID: 36111456
  • Kemper, C., Ferreira, V.P., Paz, J.T., Holers, V.M., Lionakis, M.S., and Alexander, J.J. 2023. Complement: The Road Less Traveled. J. Immunol. 210:119-125. PMCID: PMC10038130
  • Holers, V. M. 2023. Complement therapeutics are coming of age in rheumatology. Nat. Rev. Rheumatol. 19:470-485. PMID: 37337038.
  • Holers, V. M. 2023. Are there causal mucosal drivers in the preclinical development of rheumatoid arthritis? Semin. Art. Rheum. doi: 10.1016/j.semarthrit.2023.152324.
  • Fechtner, S., Berens, H., Bemis, E., Johnson, R.L., Guthridge, C.J., Carlson, N.E., Demoruelle, M.K., Harley, J.B., Edison, J.D., Norris, J.A., Robinson, W.H., Deane, K.D., James, J.A., and Holers, V.M. 2022. Antibody responses to Epstein-Barr virus in the preclinical period of rheumatoid arthritis suggest the presence of increased viral reactivation cycles. Arth. Rheum. 74:597-603. PMCID: PMC8957485
  • Okamoto, Y., Devoe, S., Seto, N., Minarchick, V., Wilson, T., Rothfuss, H.M., Mohning, M.P., Arbet, J., Kroehl, M., Visser, A., August, J., Thomas, S.M., Charry, L.L., Fleischer, C., Feser, M.L., Frazer-Abel, A.A., Norris, J.M., Cherrington, B.D., Janssen, W.J., Kaplan, M.J., Deane, K.D., Holers, V.M., and Demoruelle, M.K. 2022. Association of sputum neutrophil extracellular trap subsets with IgA anti-citrullinated protein antibodies in subjects at risk for rheumatoid arthritis. Arth. Rheum. 74:38-48. PMCID: PMC8712364
  • Schriek, P., Ching, A.C., Moily, N.S., Moffat, J., Beattie, L., Steiner, T.M., Hosking, L.M., Thurman, J.M., Holers, V.M., Ishido, S., Lahoud, M.H., Caminschi, I., Heath, W.R., Mintern, J.D., and Villadangos, J.A. 2022. Marginal zone B cells acquire dendritic cell functions by trogocytosis. Science 375(6581):eabf7470. doi: 10.1126/science.abf7470. PMID: 35143312
  • Wong, C.J., Wang, L., Holers, V.M., Frazer-Abel, A., van der Maarel, S.M., Tawil, R., Statland, J.M., and Tapscott, S.J. 2022. Elevated plasma complement components in facioscapulohumeral dystrophy. Hum. Mol. Genet. 31:1821-1829. PMCID: PMC 9169453
  • Sasaki, T., Bracero, S., Keegan, J., Chen, L., Cao, Y., Stevens, E., Qu, Y., Wang, G., Nguyen, J., Sparks, J.A., Holers, V.M., Alves, S.E., Lederer, J.A., Costenbader, K.H., and Rao, D.A. 2022. Longitudinal immune cell profiling in early systemic lupus erythematosus. Arth. Rheum. 74:1808-1821. PMID: 35644031
  • Wagner, B.D., Patnaik, J.L., Palestine, A.G., Frazer-Abel, A.A., Baldermann, R., Holers, V.M., Mathias, M.T., Mandava, N., and Lynch, A.M. 2022. Association of systemic inflammatory factors with progression to advanced age-related macular degeneration. Ophthal. Epidemiol. 29:139-148. PMCID: PMC8497647
  • Smith, J.M., Mandava, N., Tirado-Gonzalez, V., Garcia-Santisteban, R., Geiger, M.D., Patnaik, J.L., Frazer-Abel, A., Lynch, A.M., Mandava, N., Holers, V.M., Wagner, B.D., Sanchez-Santos, I., Meizner, D., Quiroz-Mercado, H., and Palestine, A.G. 2022. Correlation of complement activation in aqueous and vitreous in patients with proliferative diabetic retinopathy. Transl. Vis. Sci. Technol. doi: 10.1167/tvst.11.4.13. PMCID: PMC9034714
  • Marin, A.I., Poppelaars, F., Wagner, B.D., Palestine, A.G., Patnaik, J.L., Holers, V.M., Frazer-Abel, A.A., Mathias, M.T., Manoharan, N., Fonteh, C.N., Mandava, N., Lynch, A.M., and University of Colorado Retina Research Group. 2022. Sex and age-related differences in complement factors among patients with intermediate age-related macular degeneration. Transl. Vis. Sci. Technol. doi: 10.1167/tvst.11.5.22. PMCID: PMC9145081
  • Fahnoe, K.C., Liu, F., Morgan, J.G., Ryan, S.T., Storek, M., Stark, E.G., Taylor, F.R., Holers, V.M., Thurman, J.M., Wawersik, S., Kalled, S.L., and Violette SM. 2022. Development and optimization of bifunctional fusion proteins to locally modulate complement activation in diseased tissue. Front Immunol. doi: 10.3389/fimmu.2022.869725. PMCID: PMC9244803
  • Bergstedt, D.T., Tarter, W.J., Peterson, R.A., Feser, M.L., Parish, M.C., Striebich, C.C., Demoruelle, M.K., Moss, L., Bemis, E.A., Norris, J.M., Holers, V.M., Edison, J.D., Thiele, G.M., Mikuls, T.R., and Deane KD. 2022. Antibodies to citrullinated protein antigens, rheumatoid factor isotypes and the shared epitope and the near-term development of clinically-apparent rheumatoid arthritis. Front Immunol. doi: 10.3389/fimmu.2022.916277. PMCID: PMC9265214
  • Banda, N.K., Deane, K.D., Bemis, E.A., Strickland, C., Seifert, J., Jordan, K., Goldman, K., Morgan, B.P., Moreland, L.W., Lewis, M.J., Pitzalis, C., and Holers V.M. 2022. Analysis of complement gene expression, clinical associations, and biodistribution of complement proteins in the synovium of early rheumatoid arthritis patients reveals unique pathophysiologic features. J. Immunol. 208:2482-2496. PMCID: PMC9133225
  • Vanderlinden, L.A., Bemis, E.A., Seifert, J., Guthridge, J.M., Young, K.A., Demoruelle, M.K., Feser, M., DeJager, W., Macwana, S., Mikuls, T.R., O'Dell, J.R., Weisman, M.H., Buckner, J., Keating, R.M., Gaffney, P.M., Kelly, J.A., Langefeld, C.D., Deane, K.D., James, J.A., Holers, V.M., and Norris, J.M. 2022. Relationship between a vitamin D genetic risk score and autoantibodies among first-degree relatives of probands with rheumatoid arthritis and systemic lupus erythematosus. Front. Immunol. doi: 10.3389/fimmu.2022.881332. PMCID:PMC9205604
  • Tsaltskan, V., Nguyen, K., Eaglin, C., Holers, V.M., Deane, K.D., and Firestein, G.S. 2022. Comparison of web-based advertising and a social media platform as recruitment tools for underserved and hard-to-reach populations in rheumatology clinical research. ACR Open Rheumatol. 4:623-630. PMCID: PMC9274346
  • Chriswell, M.E., Lefferts, A.R., Clay, R.R., Hsu, A.R., Seifert, J., Feser, M.L., Rims, C., Bloom, M.S., Bemis, E.A., Li, S., Maerz, M.D., Frank, D.N., Demoruelle, M.K., Deane, K.D., James, E.A., Buckner, J.H., Robinson, W.H., Holers, V.M., and Kuhn, K.A. 2022. Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum. Science Translational Medicine. doi: 10.1126/scitranslmed.abn5166. Epub 2022 Oct 26 PMID: 36288282
  • Seifert, J.A., Bemis, E.A., Ramsden, K., Lowell, C., Polinski, K., Fleischer, C., Demoruelle, M.K., Buckner, J., Gregersen, P.K., Keating, R.M., Mikuls, T.R., O’Dell, J.R., Weisman, M.H., Deane, K.D., Norris, J.M., Steere, A.C., and Holers, V.M. 2022. Association of antibodies to Prevotella copri in anti-CCP-positive individuals at-risk for developing rheumatoid arthritis and in those with early or established rheumatoid arthritis. Arth. Rheum. doi: 10.1002/art.42370. PMID: 36259174
  • Renner, B., Laskowski, J., Poppelaars, F., Ferreira, V.P., Blaine, J., Antonioli, A.H., Hannan, J.P., Kovacs, J.M., van Kooten, C., You, Z., Pickering, M.C., Holers, V.M., and Thurman, J.M. 2022. Factor H related proteins modulate complement activation on kidney cells. Kidney Intl. 102:1331-1344. PMCID: PMC9691546
  • Holers, V.M., Kuhn, K.A., Demoruelle, M.K., Norris, J.M., Firestein, G.S., James, E.A., Robinson, W.H., Buckner, J.H., and Deane, K.D. 2022. Mechanism-driven strategies for prevention of rheumatoid arthritis. Rheumatol. Autoimmun. 2: 109-119. PMCID: PMC9610829
  • Holers, V.M. 2022. Contributions of animal models to mechanistic understandings of antibody-dependent disease and roles of the amplification loop. Immunol. Rev. doi: 10.1111/imr.13136. PMID: 36111456
  • Olsen, N.J., Okuda, D.T., Holers, V.M., and Karp, D.R. 2022. Editorial: Understanding the concept of pre-clinical autoimmunity. Front. Immunol. doi: 10.3389/fimmu.2022.983310. PMCID: PMC9355672
  • West, S.G., and Holers, V.M. 2022. Clinical academic rheumatology: Still getting more than you pay for. Arth. Care Res. 74:1039-1040. PMID: 36194068
  • Banda, N.K., Tomlinson, S., Scheinman, R.I., Ho, N., Ramirez, J.R., Mehta, G., Wang, G., Vu, V.P., Simberg, D., Kulik, L., and Holers, V.M. 2020. C2 IgM natural antibody enhances inflammation and its use in the recombinant single chain antibody-fused complement inhibitor C2-Crry to target therapeutics to joints attenuates arthritis in mice. Front. Immunol. 11:575154. PMCID: PMC7596757
  • Bemis, E.A., Demoruelle, M.K., Seifert, J.A., Polinski, K.J., Weisman, M.H., Buckner, J.H., Gregersen, P.K., Mikuls, T.R., O’Dell, J.R., Keating, R.M., Deane, K.D., Holers, V.M., and Norris, J.M. 2021. Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting. Ann. Rheum. Dis. 80:154-161 PMCID: PMC7855648
  • Juge, P.-A., Lee, J.S., Lau, J., Kawano-Dourado, L. … Holers, V.M., …and Dieude, P. 2021. Methotrexate and rheumatoid arthritis associated interstitial lung disease. Eur. Respir. J. Feb 11;57(2):2000337. PMCID: PMC8212188
  • Takahashi, Kl, Banda, N.K., Holers, V.M., and Van Cott, E.M. 2021. Complement component factor B has thrombin-like activity. Biochem. Biophys. Res. Comm. 552:17-22. PMCID: PMC8035301
  • Demoruelle, M.K., Wang, H., Davis, R.L., Visser, A., Hoang, J., Norris, J.M., Holers, V.M., Deane, K.D., and Darrah, E. 2021. Anti-peptidyl deiminase-4 antibodies at mucosal sites can activate peptidylarginine deiminase-4 enzyme activity in rheumatoid arthritis. Arth. Res.Ther. 23(1):163. PMCID: PMC8182933
  • Li, C., Patel, K., Tu, Z., Yang, X., Kulik, L., Alawieh, A., Allen, P., Cheng, Q., Wallace, C., Kilkenny, J., Kwon, J., Gibney, B., Cantu, E,. Sharma, A., Pipkin, M., Machuca, T., Emtiazjoo, A., Goddard, M., Holers, V.M., Nadig, S., Christie, J., Tomlinson, S., and Atkinson, C. 2021. A novel injury site-natural antibody targeted complement inhibitor protects against lung transplant injury. Am. J.Transplant. 21:2067-2078. PMCID: PMC8246004
  • Polinski, K.J., Armstrong, M., Manke, J., Seifert, J., Crume, T., Yang, F., Clare-Salzler, M., Holers, V.M., Reisdorph, N., and Norris, J.M. 2021. Collection and storage of human plasma for measurement of oxylipins. Metabolites 11(3):137. PMCID: PMC7996814
  • Polinski, K.J., Bemis, E.A., Yang, F., Crume, T., Demoruelle, M.K., Feser, M., Seifert, J., O'Dell, J.R., Mikuls, T.R., Weisman, M.H., Gregersen, P.K., Keating, R.M., Buckner, J., Reisdorph, N., Deane, K.D., Clare-Salzler, M., Holers. V.M., and Norris, J.M. 2021. Association of lipid mediators with development of future incident inflammatory arthritis in an anti-citrullinated protein antibody-positive population. Arth. Rheum. 73:955-962. PMCID: PMC8169523
  • Mangalea, M.R., Paez-Espino, D., Kieft, K., Chatterjee, A., Chriswell, M.E., Seifert, J.A., Feser, M.L., Demoruelle, M.K., Sakatos, A,. Anantharaman, K., Deane, K.D., Kuhn, K.A., Holers, V.M., and Duerkop, B.A. 2021. Individuals at-risk for rheumatoid arthritis harbor differential intestinal bacteriophages communities with distinct metabolic potential. Cell Host Microbe 29:726-739.e5. PMCID: PMC8186507
  • Okamato, Y., Ghosh, T., Okamoto, T., Schuyler, R.P., Seifert, J., Charry, L.L., Visser, A., Feser, M., Fleischer, C., Pedrick, C., August, J., Moss, L., Bemis, E.A., Norris, J.M., Kuhn, K.A., Demoruelle, M.K., Deane, K.D., Ghosh, D., Holers, V.M.*, and Hsieh, E.W.Y.* 2021. Subjects at-risk for future development of rheumatoid arthritis demonstrate a PAD4- and TLR-dependent enhanced histone H3 citrullination and proinflammatory cytokine production in CD14hi monocytes. J. Autoimmunity. 117:102581. *co-senior authors PMCID: PMC7855988
  • Wagner, B.D., Patnaik, J.L., Palestine, A.G., Frazer-Abel, A.A., Baldermann, R., Holers, V.M., Mathias, M.T., Mandava, N., and Lynch, A.M. 2021. Association of systemic inflammatory factors with progression to advanced age-related macular degeneration. Ophthal. Epid. 1-10, Apr 08. PMCID: PMC8497647
  • Bettner, L.F., Peterson, R.A., Bergstedt, D.T., Kelmenson, L.B., Demoruelle, M.K., Mikuls, T.R., Edison, J.D., Parish, M.C., Feser, M.L., Frazer-Abel, A.A., Moss, L.K., Mahler, M., Holers, V.M., and Deane, K.D. 2021. Combinations of anti-cyclic citrullinated protein antibody, rheumatoid factor, and serum calprotectin positivity are associated with the diagnosis of rheumatoid arthritis within 3 years. ACR Open Rheum. doi: 10.1002/acr2.11309. PMID: 34288565
  • Hughes-Austin, J.M., Ix, J.H., Ward, S.R., Weisman, M.H., O’Dell, J.R., Mikuls, T.R., Buckner, J.H., Gregersen, P.K., Keating, R.M., Demoruelle, M.K., Deane, K.D., Holers, V.M., and Norris, J.M. 2021. Evaluating associations of joint swelling, joint stiffness and joint pain with physical activity in first-degree relatives of patients with rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA), a prospective cohort study. BMJ Open 11(9):e050883. PMCID: PMC8442039
  • Trachtman, H., Laskowski, J., Lee, C., Renner, B., Feemster, A., Parikh, S., Panzer, S.E., Zhong, W., Cravedi, P., Cantarelli, C., Kulik, L., You, Z., Satchell, S., Rovin, B., Liu, F., Kalled, S.L., Holers, V.M., Jalal, D., and Thurman, J.M. 2021. Natural antibody and complement activation characterize patients with idiopathic nephrotic syndrome. Am. Journal of Physiology - Renal Physiology 321:F505-F516. PMCID: PMC8560405
  • Mankia, K., Siddle, H.J., Kerschbaumer, A., Alpizar Rodriguez, D., Catrina, A.I., Canete, J.D., Cope, A.P., Daien, C.I., Deane, K.D., El Gabalawy, H., Finckh, A., Holers, V.M., Koloumas, M., Ometto, F., Raza, K., Zabalan, C., van der Helm-van Mil, A., van Schaardenburg, D., Aletaha, D., and Emery, P. 2021. EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis. Ann. Rheum. Dis. 80:1286-1298. PMCID: PMC8458095
  • Wahid, A.A., Dunphy, R.W., Macpherson, A., Gibson, B.G., Kulik, L., Whale, K., Back, C., Hallam, T.M., Alkhawaja, B., Martin, R.L., Meschede, I., Laabei, M., Lawson, A.D.G., Holers, V.M., Watts, A.G., Crennell, S.J., Harris, C.L., Marchbank, K.J., and van den Elsen, J.M.H. Insights into the structure-function relationships of dimeric C3d fragments. 2021. Front. Immunol. 12:714055. PMCID: PMC8381054
  • Fechtner, S., Berens, H., Bemis, E., Johnson, R.L., Guthridge, C.J., Carlson, N.E., Demoruelle, M.K., Harley, J.B., Edison, J.D., Norris, J.A., Robinson, W.H., Deane, K.D., James, J.A., and Holers, V.M. 2021. Antibody responses to Epstein-Barr virus in the preclinical period of rheumatoid arthritis suggest the presence of increased viral reactivation cycles. Arth. Rheum. doi: 10.1002/art.41994 PMID: 34605217
  • Okamoto, Y., Devoe, S., Seto, N., Minarchick, V., Wilson, T., Rothfuss, H.M., Mohning, M.P., Arbet, J., Kroehl, M., Visser, A., August, J., Thomas, S.M., Charry, L.L., Fleischer, C., Feser, M.L., Frazer-Abel, A.A., Norris, J.M., Cherrington, B.D., Janssen, W.J., Kaplan, M.J., Deane, K.D., Holers, V.M., and Demoruelle, M.K. 2021. Association of sputum neutrophil extracellular trap subsets with IgA anti-citrullinated protein antibodies in subjects at risk for rheumatoid arthritis. Arth. Rheum. doi: 10.1002/art.419. PMID: 34369110
  • Deane, K.D., and Holers, V.M. 2021. Rheumatoid arthritis: Pathogenesis, prediction and prevention – an emerging paradigm shift. Arth. Rheum. 73: 181-193. PMCID: PMC7772259
  • Holers, V.M. 2021. Challenges and opportunities: Using omics to generate testable insights into pathogenic mechanisms in preclinical seropositive rheumatoid arthritis. Arth. Rheum. 73:1-4. PMID: 32776474
  • Nigrovic, P.A., Colbert, R.A., Holers, V.M., Ozen, S., Ruperto, N., Thompson, S.D., Wedderburn, L.R., Yeung, R.S.M., and Martini, A. 2021. Biological classification of childhood arthritis: roadmap to a molecular nomenclature. Nature Reviews Rheumatology 17:257-269. PMID: 33731872
  • 300. Frid, M.G., McKeon, B.A., Thurman, J.M., Maron, B.A., Li, M., Zhang, H., Kumar, S., Sullivan, T., Laskowsky, J., Fini, M.A., Hu, S., Tuder, R.M., Gandjeva, A., Wilkins, M.R., Rhodes, C.J., Ghataorhe, P., Leopold, J.A., Wang, R.S., Holers, V.M., and Stenmark, K.R. 2020. Immunoglobulin-driven complement activation regulates pro-inflammatory remodeling in pulmonary hypertension. Am. J. Respir. Crit. Care Med. 201:224-239. PMCID: PMC6961755301.
  • 301. Polinski, K.J., Bemis, E.A., Feser, M., Seifert, J., Demoruelle, M.K., Striebich, C.C., Brake, S., O'Dell, J.R., Mikuls, T.R., Weisman, M.H., Gregersen, P.K., Keating, R.M., Buckner, J., Nicassio, P., Holers, V.M., Deane, K.D., and Norris, J.M. 2020. Perceived stress and inflammatory arthritis: a prospective investigation in the Studies of the Etiologies of Rheumatoid Arthritis (SERA) cohort. Arth. Care Res. 72:1766-1771. PMCID: PMC7145743
  • 302. Lynch, A.M., Mandava, N., Patnaik, J.L., Frazer-Abel, A.A., Wagner, B.D., Palestine, A.G., Mathias, M.T., Siringo, F.S., Cathcart, J.N., and Holers, V.M. 2020. Systemic activation of the complement system in patients with advanced age-related macular degeneration. Eur. J. Ophthal. 30:1061-1068. PMID: 31203676
  • 303. Kelmenson, L.B., Wagner, B.D., McNair, B.K., Frazer-Abel, A., Demoruelle, M.K., Bergstedt, D.T., Feser, M.L., Moss, L.K., Parish, M.C., Mewshaw, E.A., Mikuls, T.R., Edison, J.D., Holers, V.M., and Deane, K.D. 2020. Timing of elevations of autoantibody isotypes in rheumatoid arthritis prior to disease diagnosis. Arth. Rheum. 72:251-261. PMCID: PMC6994340
  • 304. James, J.A., Guthridge, J.M., Chen, H., Lu, R., Bourn, R.L., Bean, K., Munroe, M.E., Smith, M., Chakravarty, E., Baer, A.N., Noaiseh, G., Parke, A., Boyle, K., Keyes-Elstein, L., Coca, A., Utset, T., Genovese, M.C., Pascual, V., Utz, P.J., Holers, V.M., Deane, K.D., Sivils, K.L., Aberle, T., Wallace, D.J., McNamara, J., Franchimont, N., and St. Clair, E.W. 2020. Unique Sjögren's syndrome patient subsets defined by molecular features. Rheumatology 51:860-868. PMCID: PMC7188221
  • 305. Bemis, E.A., Demoruelle, M.K., Seifert, J.A., Polinski, K.J., Weisman, M.H., Buckner, J.H., Gregersen, P.K., Mikuls, T.R., O’Dell, J.R., Keating, R.M., Deane, K.D., Holers, V.M., and Norris, J.M. 2020. Factors associated with progression to inflammatory arthritis in first-degree relatives of individuals with RA following autoantibody positive screening in a non-clinical setting. Ann. Rheum. Dis. doi: 10.1136/annrheumdis-2020-217066. PMID: 32928740
  • 306. Juge, P.-A., Lee, J.S., Lau, J., Kawano-Dourado, L. … Holers, V.M., …and Dieude, P. 2020. Methotrexate and rheumatoid arthritis associated interstitial lung disease. Eur. Respir. J. doi: 10.1183/13993003.00337-2020. PMID: 32646919
  • 307. Mandava, N., Tirado-Gonzalez, V., Geiger, M.D., Patnaik, J.L, Frazer-Abel, A., Lynch, A.M. Mandava, N., Palestine, A.G., Holers, V.M., Wagner, J.D., Sanchez-Santos, I., Meizner, D., Quiroz-Mercado, H., and Smith, J.M. 2020. Complement activation in the vitreous of patients with proliferative diabetic retinopathy. Invest. Ophthal. Vis. Sci. 61:39. PMCID: PMC7520707
  • 308. Lynch, A.M., Palestine, A.G., Wagner, B.D., Patnaik, J.L., Frazer-Abel, A., Mathia, M.T., Siringo, F.S., Holers, V.M., and Mandava, N. 2020. Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging. BMJ. Open Ophthal. doi.org/10.1136/bmjophth-2019-000361. PMID: 32509962
  • 309. Ayyappan P., Harms, R.Z., Seifert, J.A., Bemis, E.A., Feser, M.L., Deane, K.D., Demoruelle, M.K., Mikuls, T.R., Holers, V.M., and Sarvetnick, N.E. 2020. Heightened levels of antimicrobial response factors in patients with rheumatoid arthritis. Front. Immunol. 11:427. PMCID: PMC7100537
  • 310. Holers, V.M., Borodovsky, A., Scheinman, R.I., Ho, N., Ramirez, J.R., Dobo, J., Gal, P., Lindenberger, J., Hansen, A.G., Desai, E., Pihl, R., Thiel, S., and Banda, N.K. 2020. Key components of the complement lectin pathway are not only required for the development of inflammatory arthritis but also regulate the transcription of factor D. Front. Immunol. 11:201. PMCID: PMC7046807
  • 311. Song, Y.J, Choi, I.A, Meylan, F., Demoruelle, M.K., Farley, T., Richard, A.C., Hawley, E., Botson, J., Hong, Y.J., Lee, E.Y., Mian, S.R., Hamilton, B.C., Thiele, G.M., Mikuls, T.R., Gara, N., Ward, C.D., Lamberth, S., Deane, K.D., Heller, T., Ward, M.M., Lee, D.M., Migone, T.S., Stohl, W., O’Dell, J.R., Norris, J.M., Holers, V.M., Gregersen, P., Song, Y.W., and Siegel, R.M. 2020. Circulating TNF-like protein 1A (TLA1A) is elevated in rheumatoid arthritis and depends on TNF. Arth. Res. Ther. 22:106. PMCID: PMC7204024
  • 82. Huizinga, T.W., Holers, V.M., Anolik, J., Brenner, M.B., Buckley, C.D., Bykerk, V., Connolly, S.E., Deane, K.D., Guo, J., Hodge, M., Hoffmann, S., Nestle, F., Pitzalis, C. Raychaudhuri, S., Yamamoto, K., Li, Z., Klareskog, L. 2020. Disruptive innovation in rheumatology: new networks of global public-private partnerships are needed to take advantage of scientific progress. Ann. Rheum. Dis. 79:553-555. PMID: 32139419
  • 83. Deane, K.D., and Holers, V.M. 2020. Rheumatoid arthritis: Pathogenesis, prediction and prevention – an emerging paradigm shift. Arth. Rheum. DOI: 10.1002/art.41417. PMID: 32602263
  • 84. Holers, V.M. 2020. Challenges and opportunities: Using omics to generate testable insights into pathogenic mechanisms in preclinical seropositive rheumatoid arthritis. Arth. Rheum. DOI: 10.1002/art.41479. PMID: 32776474
  • Willis VC, Banda NK, Cordova KN, Chandra PE, Robinson WH, Cooper DC, Lugo D, Mehta G, Taylor S, Tak PP, Prinjha RK, Lewis HD, Holers VM. Protein arginine deiminase 4 inhibition is sufficient for the amelioration of collagen-induced arthritis. Clin Exp Immunol. 2017 May;188(2):263-274. PubMed PMID: 28128853
  • Gan RW, Demoruelle MK, Deane KD, Weisman MH, Buckner JH, Gregersen PK, Mikuls TR, O'Dell JR, Keating RM, Fingerlin TE, Zerbe GO, Clare-Salzler MJ, Holers VM, Norris JM. Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis. Ann Rheum Dis. 2017 Jan;76(1):147-152. PubMed PMID: 27190099
  • Demoruelle MK, Harrall KK, Ho L, Purmalek MM, Seto NL, Rothfuss HM, Weisman MH, Solomon JJ, Fischer A, Okamoto Y, Kelmenson LB, Parish MC, Feser M, Fleischer C, Anderson C, Mahler M, Norris JM, Kaplan MJ, Cherrington BD, Holers VM, Deane KD. Anti-Citrullinated Protein Antibodies Are Associated With Neutrophil Extracellular Traps in the Sputum in Relatives of Rheumatoid Arthritis Patients. Arthritis Rheumatol. 2017 Jun;69(6):1165-1175. PubMed PMID: 28182854
  • Birru Talabi M, Mackey RH, Kuller LH, Dorman JS, Deane KD, Robinson WH, Walitt BT, Chang Y, Holers VM, Liu S, Moreland LW. Human Leukocyte Antigen Shared Epitope and Inflammation, Cardiovascular Disease, Cancer, and Mortality Among Postmenopausal Women in the Women's Health Initiative Rheumatoid Arthritis Study. Am J Epidemiol. 2017 Jul 15;186(2):245-254. PubMed PMID: 28459968
  • Banda NK, Acharya S, Scheinman RI, Mehta G, Takahashi M, Endo Y, Zhou W, Farrar CA, Sacks SH, Fujita T, Sekine H, Holers VM. Deconstructing the Lectin Pathway in the Pathogenesis of Experimental Inflammatory Arthritis: Essential Role of the Lectin Ficolin B and Mannose-Binding Protein-Associated Serine Protease 2. J Immunol. 2017 Sep 1;199(5):1835-1845. PubMed PMID: 28739878
  • Wang G, Griffin JI, Inturi S, Brenneman B, Banda NK, Holers VM, Moghimi SM, Simberg D. In Vitro and In Vivo Differences in Murine Third Complement Component (C3) Opsonization and Macrophage/Leukocyte Responses to Antibody-Functionalized Iron Oxide Nanoworms. Front Immunol. 2017;8:151. PubMed PMID: 28239384
  • Gan RW, Bemis EA, Demoruelle MK, Striebich CC, Brake S, Feser ML, Moss L, Clare-Salzler M, Holers VM, Deane KD, Norris JM. The association between omega-3 fatty acid biomarkers and inflammatory arthritis in an anti-citrullinated protein antibody positive population. Rheumatology (Oxford). 2017 Dec 1;56(12):2229-2236. PubMed PMID: 29029330
  • Renner B, Tong HH, Laskowski J, Jonscher K, Goetz L, Woolaver R, Hannan J, Li YX, Hourcade D, Pickering MC, Holers VM, Thurman JM. Annexin A2 Enhances Complement Activation by Inhibiting Factor H. J Immunol. 2016 Feb 1;196(3):1355-65. PubMed PMID: 26729803
  • Gan RW, Young KA, Zerbe GO, Demoruelle MK, Weisman MH, Buckner JH, Gregersen PK, Mikuls TR, O'Dell JR, Keating RM, Clare-Salzler MJ, Deane KD, Holers VM, Norris JM. Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study. Rheumatology (Oxford). 2016 Feb;55(2):367-76. PubMed PMID: 26370400
  • Lynch AM, Wagner BD, Deterding RR, Giclas PC, Gibbs RS, Janoff EN, Holers VM, Santoro NF. The relationship of circulating proteins in early pregnancy with preterm birth. Am J Obstet Gynecol. 2016 Apr;214(4):517.e1-8. PubMed PMID: 26576488
  • Rich MC, Keene CN, Neher MD, Johnson K, Yu ZX, Ganivet A, Holers VM, Stahel PF. Site-targeted complement inhibition by a complement receptor 2-conjugated inhibitor (mTT30) ameliorates post-injury neuropathology in mouse brains. Neurosci Lett. 2016 Mar 23;617:188-94. PubMed PMID: 26892188
  • Lynch AM, Wagner BD, Giclas PC, West NA, Gibbs RS, Holers VM. The Relationship of Longitudinal Levels of Complement Bb During Pregnancy with Preeclampsia. Am J Reprod Immunol. 2016 Feb;75(2):104-11. PubMed PMID: 26510395
  • Laskowski J, Renner B, Le Quintrec M, Panzer S, Hannan JP, Ljubanovic D, Ruseva MM, Borza DB, Antonioli AH, Pickering MC, Holers VM, Thurman JM. Distinct roles for the complement regulators factor H and Crry in protection of the kidney from injury. Kidney Int. 2016 Jul;90(1):109-22. PubMed PMID: 27165610
  • Kinslow JD, Blum LK, Deane KD, Demoruelle MK, Okamoto Y, Parish MC, Kongpachith S, Lahey LJ, Norris JM, Robinson WH, Holers VM. Elevated IgA Plasmablast Levels in Subjects at Risk of Developing Rheumatoid Arthritis. Arthritis Rheumatol. 2016 Oct;68(10):2372-83. PubMed PMID: 27273876
  • Wang G, Chen F, Banda NK, Holers VM, Wu L, Moghimi SM, Simberg D. Activation of Human Complement System by Dextran-Coated Iron Oxide Nanoparticles Is Not Affected by Dextran/Fe Ratio, Hydroxyl Modifications, and Crosslinking. Front Immunol. 2016 Oct 10;7:418. PubMed PMID: 27777575
  • Chang HH, Liu GY, Dwivedi N, Sun B, Okamoto Y, Kinslow JD, Deane KD, Demoruelle MK, Norris JM, Thompson PR, Sparks JA, Rao DA, Karlson EW, Hung HC, Holers VM, Ho IC. A molecular signature of preclinical rheumatoid arthritis triggered by dysregulated PTPN22. JCI Insight. 2016 Oct 20;1(17):e90045. PubMed PMID: 27777982
  • Hannan JP, Laskowski J, Thurman JM, Hageman GS, Holers VM. Mapping the Complement Factor H-Related Protein 1 (CFHR1):C3b/C3d Interactions. PLoS One. 2016 Nov 4;11(11):e0166200. PubMed PMID: 27814381
  • Banda NK, Acharya S, Scheinman RI, Mehta G, Coulombe M, Takahashi M, Sekine H, Thiel S, Fujita T, Holers VM. Mannan-Binding Lectin-Associated Serine Protease 1/3 Cleavage of Pro-Factor D into Factor D In Vivo and Attenuation of Collagen Antibody-Induced Arthritis through Their Targeted Inhibition by RNA Interference-Mediated Gene Silencing. J Immunol. 2016 Nov 1;197(9):3680-3694. PubMed PMID: 27707997
  • Liang MH, Couto MC, Duarte CC, Gall V, White P, Naides S, Schumacher HR Jr, Hwang AS, Holers VM, Deane KD, Gupta S, Ho IC, Finckh A, Kopec J, Choi CB, Sayre EC. An Internet-based technique for the identification of persons with symptoms of inflammatory polyarthritis of less than 12 weeks. Clin Rheumatol. 2015 Mar;34(3):465-70. PubMed PMID: 25339123
  • Cruickshank MN, Dods J, Taylor RL, Karimi M, Fenwick EJ, Quail EA, Rea AJ, Holers VM, Abraham LJ, Ulgiati D. Analysis of tandem E-box motifs within human Complement receptor 2 (CR2/CD21) promoter reveals cell specific roles for RP58, E2A, USF and localized chromatin accessibility. Int J Biochem Cell Biol. 2015 Jul;64:107-19. PubMed PMID: 25817480
  • Atkinson C, Qiao F, Yang X, Zhu P, Reaves N, Kulik L, Goddard M, Holers VM, Tomlinson S. Targeting pathogenic postischemic self-recognition by natural IgM to protect against posttransplantation cardiac reperfusion injury. Circulation. 2015 Mar 31;131(13):1171-80. PubMed PMID: 25825397
  • Mehta G, Scheinman RI, Holers VM, Banda NK. A New Approach for the Treatment of Arthritis in Mice with a Novel Conjugate of an Anti-C5aR1 Antibody and C5 Small Interfering RNA. J Immunol. 2015 Jun 1;194(11):5446-54. PubMed PMID: 25917104
  • Mackey RH, Kuller LH, Deane KD, Walitt BT, Chang YF, Holers VM, Robinson WH, Tracy RP, Hlatky MA, Eaton CB, Liu S, Freiberg MS, Talabi MB, Schelbert EB, Moreland LW. Rheumatoid Arthritis, Anti-Cyclic Citrullinated Peptide Positivity, and Cardiovascular Disease Risk in the Women's Health Initiative. Arthritis Rheumatol. 2015 Sep;67(9):2311-22. PubMed PMID: 25988241
  • Panzer SE, Laskowski J, Renner B, Kulik L, Ljubanovic D, Huber KM, Zhong W, Pickering MC, Holers VM, Thurman JM. IgM exacerbates glomerular disease progression in complement-induced glomerulopathy. Kidney Int. 2015 Sep;88(3):528-37. PubMed PMID: 25945405
  • Inturi S, Wang G, Chen F, Banda NK, Holers VM, Wu L, Moghimi SM, Simberg D. Modulatory Role of Surface Coating of Superparamagnetic Iron Oxide Nanoworms in Complement Opsonization and Leukocyte Uptake. ACS Nano. 2015 Nov 24;9(11):10758-68. PubMed PMID: 26488074
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Professional Memberships

  • American Rheumatology Research and Education Foundation, Chair, Scientific Advisory Council
  • American College of Rheumatology, Abstract Selection Subcommittees
  • American College of Rheumatology Research and Education Foundation , Member, Board of Directors

Practice Locations

Hospital Affiliation
  • University of Colorado Hospital

Specialty Information

Specialties
  • Rheumatology, Board Certification
  • Internal Medicine, Board Certification

General Information

Medical Schools:
  • MD, Washington University in St. Louis School of Medicine (1978)
Internships:
  • Washington University/Barnes-Jewish Hospital/St. Louis Children's Hospital (1979)
Residency Programs:
  • Washington University/Barnes-Jewish Hospital/St. Louis Children's Hospital, Internal Medicine (1981)
Fellowships:
  • Washington University/Barnes-Jewish Hospital/St. Louis Children's Hospital, Rheumatology (1985)
  • University of Colorado, Rheumatology (1983)
Languages: English
Department: Medicine-Rheumatology
Contact Us
CU Anschutz
Fitzsimons Building

13001 East 17th Place
Campus Box C290
Aurora, CO 80045

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