University of Wisconsin
School of Medicine and Public Health

Shelef Lab

Miriam Shelef, MD, PhD | Rheumatoid arthritis research

Miriam Shelef, MD, PhD, is an immunologist and a rheumatologist with a research program focused on solving the mysteries of how and why systemic autoimmunity develops and persists in order to guide the discovery of better clinical tests and improved treatments. To this end, there are currently two major research directions in the lab. First, her research group aims to define the role of citrullination and the citrullinating peptidylarginine deiminase enzymes in immunity, inflammation, and arthritis. Second, her research team uses traditional methodology and cutting-edge high density array technology with innovative statistical methods to discover new autoantibody targets as well as novel features of antibody and autoantibody reactivity in rheumatoid arthritis, systemic lupus erythematosus, and other autoimmune diseases. Her research is and has been supported by the Rheumatology Research Foundation, the NIH NIAMS, the Wisconsin Partnership Program, the Doris Duke Charitable Foundation, the Congressionally Directed Medical Research Programs, and the University of Wisconsin.

Selected Publications

  • Sun B, Chang HH, Salinger A, Tomita B, Bawadekar M, Holmes CL, Shelef MA, Weerapana E, Thompson PR, Ho IC. Reciprocal regulation of Th2 and Th17 cells by PAD2-mediated citrullination. JCI Insight. 2019 Nov 14;4(22). pii: 129687.
  • Zheng Z, Mergaert AM, Fahmy L, Bawadekar M, Holmes CL, Ong I, Bridges AJ, Newton MA, Shelef MA. Disordered Antigens and Epitope Overlap Between Anti-Citrullinated Protein Antibodies and Rheumatoid Factor in Rheumatoid Arthritis. Arthritis Rheumatol. 2019. In Press.
  • Mergaert AM, Bawadekar M, Nguyen TQ, Massaranti L, Holmes CL, Rebernick R, Schrodi SJ, and Shelef MA. Reduced anti-histone antibodies and increased risk of rheumatoid arthritis associated with a single nucleotide polymorphism in PADI4 in North Americans. International Journal of Molecular Sciences. 2019 Jun; 20(12): 3093.
  • Holmes CL, Peyton CG, Bier AM, Donlon TZ, Osman F, BartelsCM, Shelef MA. Reduced IgG titers against pertussis in rheumatoid arthritis: evidence for a citrulline-biased immune response and medication effects. PLoS One. 2019. May 28;14(5):e0217221.
  • Holmes CL, Shim D, Kernien J, Johnson CJ, Nett JE, Shelef MA. Insight into neutrophil extracellular traps through systematic evaluation of citrullination and peptidylarginine deiminases. Journal of Immunology Research. 2019. Mar 12;2019:2160192.
  • Shelef MA. New Relationships for Old Autoantibodies in Rheumatoid Arthritis. Arthritis Rheumatol. 2019 Sep;71(9):1396-1399.
  • Rebernick R, Fahmy L, Glover C, Bawadekar M, Shim D, Holmes CL, Rademacher N, Potluri H, Bartels CM, Shelef MA. DNA Area and NETosis Analysis (DANA): A High-Throughput Method to Quantify NETosis in Fluorescent Microscope Images. Biological Procedures Online. 2018 Apr 1;20:7.
  • Sun B, Dwivedi N, Bechtel TJ, Paulsen JL, Muth A, Bawadekar M, Li G, Thompson PR, Shelef MA, Schiffer CA, Weerapana E, Ho IC. Citrullination of NF-kB p65 promotes its nuclear localization and TLR-induced expression of IL-1b and TNFa. Science Immunology. 2017; 2(12): eeal3062
  • Bawadekar M, Shim D, Johnson CJ, Warner TF, Rebernick R, Damgaard D, Nielsen CH, Pruijn GJM, Nett JE, Shelef, MA. Peptidylarginine Deiminase 2 is Required for Tumor Necrosis Factor Alpha-Induced Citrullination and Arthritis, but Not Neutrophil Extracellular Trap Formation. Journal of Autoimmunity. 2017. Feb 7. [Epub ahead of print] (PMC in Process)
  • Bawadekar M, Gendron-Fitzpatrick A, Rebernick R, Shim D, Warner TF, Nicholas AP, Lundblad LK, Thompson PR, Shelef MA. Tumor necrosis factor alpha, citrullination, and peptidylarginine deiminase 4 in lung and joint inflammation. Arthritis Res Ther. 2016 Jul 22;18(1):173. (PMC4957385)
  • Moussavi-Harami SF, Mladinich KM, Sackmann EK, Shelef MA, Starnes TW, Guckenberger DJ, Huttenlocher A, Beebe DJ. Microfluidic Device for Simultaneous Analysis of Neutrophil Extracellular Traps and Production of Reactive Oxygen Species. Integrative Biology. 2016 Feb 15;8(2):243-252.
  • Shelef MA, Bennin DA, Yasmin N, Warner TF, Ludwig T, Beggs HE, Huttenlocher A. Focal adhesion kinase is required for synovial fibroblast invasion, but not murine inflammatory arthritis. Arthritis Res Ther. 2014 Oct 4;16(5):464. (PMC4203874)
  • Shelef MA, Sokolove J, Robinson WH, Huttenlocher A. Reply (to Insights Into the Significance of Peptidylarginine Deiminase 4 and Antibodies Against Citrullinated Antigens in the Absence of "True ACPAs" in an Experimental Model of Arthritis: Comment on the Article by Shelef et al.) Arthritis Rheumatol. 2014 Sep;66(9):2644-5. (PMC Exempt. Not peer-reviewed.)
  • Shelef MA, Sokolove J, Lahey LJ, Wagner CA, Sackmann EK, Warner TF, Wang Y, Beebe DJ, Robinson WH, Huttenlocher A. Peptidylarginine Deiminase 4 Contributes to Tumor Necrosis Factor alpha-Induced Inflammatory Arthritis. Arthritis and Rheumatology. 2014 Jun;66(6):1482-91. (PMC4148484)
  • Shelef MA, Tauzin S, Huttenlocher A. Neutrophil migration; moving from zebrafish models to human autoimmunity. Immunol Rev. 2013 Nov;256(1):269-81. (PMC4117680)
  • Shelef MA, Bennin DA, Mosher DF, Huttenlocher A, Citrullination of Fibronectin Modulates Synovial Fibroblast Behavior. Arthritis Res Ther. 2012 Nov 5;14(6):R240. (PMC3674601)
  • Sackmann EK, Berthier E, Young EW, Shelef MA, Wernimont SA, Huttenlocher A, Beebe DJ. Microfluidic kit-on-a-lid: a versatile platform for neutrophil chemotaxis assays. Blood. 2012 Oct 4;120(14):e45-53. (PMC3466974)
  • Omori SA, Cato MH, Anzelon-Mills A, Puri KD, Shapiro-Shelef M, Calame K, and Rickert RC. Regulation of class-switch recombination and plasma cell differentiation by phosphatidylinositol 3-kinase signaling. Immunity. 2006 Oct;25(4):545-57
  • Martins GA*, Cimmino L*, Shapiro-Shelef M*, Szabolcs M, Herron A, Magnusdottir E, Calame K. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. Nat Immunol. 2006 May;7(5):457-65. (*co-first authors)
  • Shapiro-Shelef M, Lin K-I, Savitsky D, Liao J, and Calame K, Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow. J Exp Med. 2005 Dec 5;202(11):1471-6.
  • Johnson K, Shapiro-Shelef M, Tunyaplin C, Calame K. Regulatory events in early and late B-cell differentiation. Mol Immunol. 2005 May;42(7):749-61.
  • Shapiro-Shelef M, Calame K. Regulation of plasma-cell development. Nat Rev Immunol. 2005 Mar;5(3):230-42.
  • Vincent SD, Dunn NR, Sciammas R, Shapiro-Shelef M, Davis MM, Calame K, Bikoff EK, Robertson EJ. The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse. Development. 2005 Mar;132(6):1315-25.
  • Shaffer AL, Shapiro-Shelef M, Iwakoshi NN, Lee AH, Qian SB, Zhao H, Yu X, Yang L, Tan BK, Rosenwald A, Hurt EM, Petroulakis E, Sonenberg N, Yewdell JW, Calame K, Glimcher LH, Staudt LM. XBP1, downstream of Blimp-1, expands the secretory apparatus and other organelles, and increases protein synthesis in plasma cell differentiation. Immunity. 2004 Jul;21(1):81-93.
  • Shapiro-Shelef M and Calame K. Plasma cell differentiation and multiple myeloma. Curr Opin Immunol. 2004 Apr;16(2):226-34.
  • Shapiro-Shelef M, Lin KI, McHeyzer-Williams LJ, Liao J, McHeyzer-Williams MG, Calame K. Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells. Immunity. 2003 Oct;19(4):607-20.
  • Tunyaplin C, Shapiro MA, Calame KL. Characterization of the B lymphocyte-induced maturation protein-1 (Blimp-1) gene, mRNA isoforms and basal promoter. Nucleic Acids Res. 2000 Dec 15;28(24):4846-55.
  • Hahn ME, Karchner SI, Shapiro MA, Perera SA. The Aryl Hydrocarbon Receptor in Early Vertebrates. Mar Environ Res. 1998. 46(1-5);41-44.
  • Hahn ME, Karchner SI, Shapiro MA, Perera SA. Molecular evolution of two vertebrate aryl hydrocarbon (dioxin) receptors (AHR1 and AHR2) and the PAS family. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13743-8.
  • Evans SM, Jenkins WT, Shapiro M, Koch CJ. Evaluation of the concept of "hypoxic fraction" as a descriptor of tumor oxygenation status. Adv Exp Med Biol.1997;411:215-25.
  • Shapiro MA, Rawa J, Silverton SF. Osteoclast Pit Volumes as a Measure of Calcified Substrate Resorption. J Dent Res. 1995;74:119.
  • Shapiro M, Howard D, Silverton SF. Osteoclast Pit Volumes Standardized by Atom Force Microscopy are Decreased by Ethoxzolamide. Cells and Materials. 1994;4(4):371-78.