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Daniel L. Mueller, M.D.
Professor
Director of Rheumatic and Autoimmune Diseases
Department of Medicine
University of Wisconsin - Madison, 1983, M.D.
muell002@umn.edu
612-625-8477 - office
612-625-8614 - lab
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Research Interests:
T cell immune tolerance
T cell clonal expansion
Control of T cell function by histone modification
Dr. Daniel Mueller is a Professor of Medicine, and Chief 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 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 is also the Director 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 maintenance of
T-cell tolerance within the peripheral immune system.
Current Research being conducted:
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 lead to its functional
inactivation (clonal anergy) and T-cell tolerance. Chronic
antigen recognition in the absence of costimulatory ligands
normally leads to clonal anergy induction, rather than aggressive
immunity. This does not appear to be true, however, for individuals
who are lymphopenic, where antigen recognition invariably
leads to an expansion of the clone, continued functional responsiveness,
and in some cases immunopathology such as autoimmune arthritis.
Recent experimental observations from his laboratory, and
others, have suggested a role for single chain E3 ligases
in this counter-regulation of clonal expansion and induction
of clonal anergy. Other recently published studies in the
laboratory have defined the importance of ongoing antigen
recognition within peripheral tissues to facilitate the accumulation
of effector T-cells capable of inducing tissue damage. Finally,
experiments are underway that investigate the mechanisms by
which histone modifications regulate gene transcription and
promote the development of the clonal anergy state during
the avoidance of autoimmune arthritis.
Selected Recent Publications:
- Mueller DL. 2009. The problem of peripheral self-peptide-MHC
recognition: mechanisms maintaining peripheral tolerance.
Nature Immunol. In press.
- Agarwal P, Raghavan A, Nandiwada SL, Curtsinger JM, Bohjanen
PR, Mueller DL, Mescher MF. 2009. Gene regulation and chromatin
remodeling by IL-12 and type I IFN in programming for CD8
T cell effector function and memory. J.
Immunol. Aug 1;183(3):1695-704.
- Zhang R, Zhang N, Mueller DL.2008. Casitas B-lineage lymphoma
b inhibits antigen recognition and slows cell cycle progression
at late times during CD4+ T cell clonal expansion. J.
Immunol. Oct 15;181(8):5331-9.
- Obhrai JS, Oberbarnscheidt M, Zhang N, Mueller DL, Shlomchik
WD, Lakkis FG, Shlomchik MJ, Kaplan DH. 2008. Langerhans
Cells Are Not Required for Efficient Skin Graft Rejection.
J.
Invest. Dermatol. Mar 13 (Epub).
- Yarke CA, Dalheimer SL, Zhang N, Catron DM, Jenkins MK,
and Mueller DL. 2008. Proliferating CD4+ T cells undergo
immediate growth arrest upon cessation of TCR signaling
in vivo. J.
Immunol. 180:156-162.
- Richards DM, Zhang N, Dalheimer SL, and Mueller DL. 2007.
Allopeptide–specific CD4+ T cells help directly alloreactive
graft–infiltrating CD8+ T cells in the absence of
APC licensing. Am.
J. Transplant. 7:2269-2278.
- Mondino A, and Mueller DL. 2007. mTOR at the crossroads
of T cell proliferation and tolerance. Sem.
Immunol. 9:162-172.
- Mueller DL. 2007. Molecular mechanisms supporting peripheral
T cell tolerance: Potential therapeutic approaches to autoimmunity
and allograft rejection. Sem.
Immunol. 19:139.
- Nandiwada SL, Li W, Zhang R, and Mueller DL. 2006. p300/Cyclic
AMP-responsive element binding (CREB)-binding protein mediates
transcriptional co-activation by the CD28 T cell costimulatory
receptor. J.
Immunol. 177:401-413.
- Bonnevier JL, Yarke CA, and Mueller DL. 2006. Sustained
B7/CD28 interactions and resultant phosphatidylinositol
3-kinase activity maintain G1-->S phase transitions at
an optimal rate. Eur.
J. Immunol. 36:1583-1597.
- Colombetti S, Basso V, Mueller DL, and Mondino A. 2006.
Prolonged TCR/CD28 engagement drives IL-2-independent T
cell clonal expansion through signaling mediated by the
mammalian target of rapamycin. J
Immunol. 176:2730-2738.
- Dalheimer SL. Richards DM and Mueller DL: 2005. Sharing
of Class I MHC molecules between donor and host promotes
the infiltration of allografts by mHAg-reactive CD8+ T cells.
Am.
J. Transplant. 5:832-838.
- Lande JD, Dalheimer SL, Mueller DL, Hertz MI, and King
RA. 2005. Gene expression profiling in murine obliterative
airway disease. Am.
J. Transplant. 5:2170-2184.
- Bonnevier JL, Zhang R, and Mueller DL. 2005. E3 ubiquitin
ligases and their control of T cellautoreactivity. Arth.
Res. Ther. 7:233-242.
Last updated: August 11, 2009 |
