Daniel L Mueller, MD

Professor of Medicine, Division of Rheumatic and Autoimmune Diseases

Daniel L Mueller

Contact Info

muell002@umn.edu

Office Phone 612-625-8477

Lab Phone 612-625-8614

Mailing Address:
420 Delaware ST SE
MMC 108
Minneapolis, MN 55455

Administrative Assistant Name
Susan Prause

Administrative Phone
612-624-6843

Administrative Email
sprause@umn.edu

Medical School, University of Wisconsin-Madison School of Medicine, Madison, WI

Residency, Ohio State University Hospital, Columbus, OH

Fellowship, University of Texas Southwestern Medical Center, Dallas, TX

Summary

Dr. Daniel Mueller is a Professor of Medicine, and the Director of Rheumatic and Autoimmune Diseases at the University of Minnesota Medical School. He undertook his medical studies at the University of Wisconsin-Madison School of Medicine, and later obtained his Internal Medicine training at the Ohio State University Hospital. In 1986, he received training in basic molecular immunology in the Laboratory of Immunology at the National Institute for Allergy and Infectious Disease, NIH, under Drs. Ronald Schwartz and William Paul. It is there that he initiated his research into fundamental mechanisms involved in the development and maintenance of immune self-tolerance. In 1990, Dr. Mueller entered the Rheumatology Fellowship Training Program in the Rheumatic Diseases Division/Department of Internal Medicine at the University of Texas Southwestern Medical Center, under Dr. Peter Lipsky.

Since the completion of his medical and research training, he has been on the University of Minnesota Medical School faculty. He currently holds the John F. Finn Arthritis Foundation Land Grant Chair. He is also a member of the Autoimmunity Program, within the University's Center for Immunology. The major focus of his academic program is the investigation of the biological and biochemical mechanisms that underlie the induction and maintenance of T- and B-cell tolerance within the peripheral immune system. His goal is the design of curative antigen-specific treatment strategies for autoimmune disease.

Awards & Recognition

  • Fellow American College of Rheumatology (1993)
  • Member of the American Society for Clinical Investigation (2002)

Research

Research Summary/Interests

  • Biological and biochemical nature of immune self-tolerance
  • T cell immune tolerance
  • T cell clonal expansion
  • Breakdown of B cell tolerance during autoimmune disease development
  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosus

Current Research Efforts: 

Autoimmunity develops as the consequence of a loss of tolerance to self-antigens. Investigations carried out by Dr. Daniel Mueller are leading to a better understanding of the biological and biochemical nature of immune self-tolerance. Of particular interest are those factors that determine whether prolonged and continuous antigen stimulation of a T cell will lead to an increase in the clone size and the development of protective (or pathological) effector function, or alternatively lead to functional inactivation (anergy) and T regulatory cell (Treg) differentiation. To approach this problem, Mueller's research team is currently using an assortment of genomics and bioinformatics techniques (scRNA-Seq, ATAC-Seq) to characterize gene regulatory patterns in CD4 T cells that are associated with anergy induction and Foxp3+ Treg generation. Candidate gene regulators are being interrogated within neonatal mice--a time at which peripheral tolerance induction is essential for the avoidance of autoimmunity.

Loss of T cell tolerance also allows for the expansion and differentiation of autoreactive B cells, and the development of B-dependent autoimmune disease. Currently, these biological principles are being investigated in models of CD4 T cell-mediated immunopathology using both monoclonal TCR-transgenic T cells as well as self-antigen specific polyclonal responder cells. Additionally, translational experiments continue to detail the repertoire of human autoreactive B cells in normal subjects as well as in patients with Rheumatoid Arthritis. Currently, experiments are exploring the role of Ig gene somatic hypermutation in the generation of arthritogenic B cells by biochemically characterizing the antigen specificity of families of autoreactive B cell antigen receptors all derived from the same B cell progenitor.

Publications

  • Sahlström P, Hansson M, Steen J, Amara K, Titcombe PJ, Forsström B, Stålesen R, Israelsson L, Piccoli L, Lundberg K, Klareskog L, Mueller DL, Catrina AI, Skriner K, Malmström V, Grönwall C. Different Hierarchies of Anti-Modified Protein Autoantibody Reactivities in Rheumatoid Arthritis. Arthritis Rheumatol. 2020 Oct;72(10):1643-1657. doi: 10.1002/art.41385. Epub 2020 Sep 10. PMID: 32501655.
  • ElTanbouly MA, Zhao Y, Nowak E, Li J, Schaafsma E, Le Mercier I, Ceeraz S, Lines JL, Peng C, Carriere C, Huang X, Day M, Koehn B, Lee SW, Silva Morales M, Hogquist KA, Jameson SC, Mueller D, Rothstein J, Blazar BR, Cheng C, Noelle RJ. VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance. Science. 2020 Jan 17;367(6475):eaay0524. doi: 10.1126/science.aay0524. PMID: 31949051; PMCID: PMC7391053.
  • Schmiel SE, Kalekar LA, Zhang N, Blankespoor TW, Robinson LJ, Mueller DL. Adenosine 2a Receptor Signal Blockade of Murine Autoimmune Arthritis via Inhibition of Pathogenic Germinal Center-Follicular Helper T Cells. Arthritis Rheumatol. 2019 May;71(5):773-783. doi: 10.1002/art.40796. Epub 2019 Mar 25. PMID: 30516351; PMCID: PMC6483839.
  • Steen J, Forsström B, Sahlström P, Odowd V, Israelsson L, Krishnamurthy A,
    Badreh S, Mathsson Alm L, Compson J, Ramsköld D, Ndlovu W, Rapecki S, Hansson M, Titcombe PJ, Bang H, Mueller DL, Catrina AI, Grönwall C, Skriner K, Nilsson P, Lightwood D, Klareskog L, Malmström V. Recognition of Amino Acid Motifs, Rather Than Specific Proteins, by Human Plasma Cell-Derived Monoclonal Antibodies to Posttranslationally Modified Proteins in Rheumatoid Arthritis. Arthritis Rheumatol. 2019 Feb;71(2):196-209. doi: 10.1002/art.40699. PMID: 30152202; PMCID: PMC6563427.
  • Lloyd KA, Wigerblad G, Sahlström P, Garimella MG, Chemin K, Steen J, Titcombe PJ, Marklein B, Zhou D, Stålesen R, Ossipova E, Lundqvist C, Ekwall O, Rönnelid J, Mueller DL, Karlsson MCI, Kaplan MJ, Skriner K, Klareskog L, Wermeling F, Malmström V, Grönwall C. Differential ACPA Binding to Nuclear Antigens Reveals a PAD-Independent Pathway and a Distinct Subset of Acetylation Cross-Reactive Autoantibodies in Rheumatoid Arthritis. Front Immunol. 2019 Jan 4;9:3033. doi: 10.3389/fimmu.2018.03033. PMID: 30662440; PMCID: PMC6328449.

Clinical

Clinics

Rheumatology Clinic;University of Minnesota Medical Center