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

  • 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
SOM Resources
CU Resources
Contact Us
(303) 724-0100
Building 500 N2229

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