Joshua D. Milner, M.D.Building 10, Room 9N208C-110 Center DriveBethesda, MD 20892Phone: 301-827-3662Fax: email@example.com
Read how NIAID scientists identified a link between Job's Syndrome and a susceptibility to viral infections.
Chief, Allergic Inflammation Unit, LAD
The Allergic Inflammation Unit (AIU) is a basic, translational, and clinical lab focused on understanding the immunology of atopic disease through patients with genetic diseases associated with atopic manifestations, patients with immune deficiency and atopy, and patients with severe atopic dermatitis. Through studies of patients and mouse models, we hope to gain better insights into the mechanisms of immunodysregulation that lead to atopic inflammatory disease.
Josh Milner and an NIAID research team have found that wet wrap therapy combined with education on long-term skin care can dramatically improve the lives of children with severe eczema.
Weak T-cell receptor (TCR)-mediated signaling of yet-undifferentiated naïve T cells can lead to inappropriate Th2 differentiation in mouse models. Insufficient TCR diversity can lead to impaired regulation of T cells by other T cells due to insufficient TCR specificity overlap of effector and regulatory populations or due to the absence of competition between T cells leading to the inappropriate emergence of weakly signaling TCRs specific for a given antigen. Our lab is developing and applying techniques to determine whether certain human disorders of atopy may be caused by defects in TCR diversity or signaling function.
Via the study of selected genetic diseases that have allergic symptoms as an associated manifestation, we hope to derive lessons in the pathophysiology of atopy from the known affected pathways. Examples of diseases studied include the autosomal dominant hyper-immunoglobulin (IgE) syndrome due to mutations in STAT3, Wiskott-Aldrich Syndrome, adenosine deaminase (ADA)-deficiency severe combined immunodeficiency disease (SCID) associated with high IgE and others.
AIU is also centrally focused on defining and understanding new genetic diseases of atopy in order to find novel pathways in the pathogenesis of allergy from these unique diseases. One example is PLCG2-associated antibody deficiency and immune dysregulation (PLAID), which we recently described. Patients with PLAID have cold urticaria, atopy, immune deficiency, and autoimmunity. Research is ongoing into the pathophysiology of PLAID and into the role of the PLCG2 and its pathway in other related disorders.
Joshua Milner graduated with an S.B. in biology from the Massachusetts Institute of Technology (MIT) in 1995 and an M.D. with distinction in immunology from the Albert Einstein College of Medicine in 2000. He was the recipient of the Pediatric Scientist Development Program Fellowship and did his fellowship in allergy and immunology at NIAID. He completed a postdoctoral fellowship with Dr. William Paul, NIAID, examining issues of mouse T-cell receptor repertoires. He was in the NIAID Clinical Research Transition Program immediately prior to being named chief of AIU as a clinical tenure-track investigator in NIAID.
John Barber, B.S. (Post-baccalaureate fellow)
Guanping Sun, Ph.D. (Biologist)
Shrimati Datta, Ph.D. (Postdoctoral fellow)
Andrea Siegel, Ph.D. (Postdoctoral fellow)
Monica Ghei Lawrence, Ph.D. (Clinical fellow)
Michelle O’Brien, R.N. (Nurse study coordinator)
Kelly Stone, M.D., Ph.D. (Staff clinician)
Ombrello MJ, Remmers EF, Sun G, Freeman AF, Datta S, Torabi-Parizi P, Subramanian N, Bunney TD, Baxendale RW, Martins MS, Romberg N, Komarow H, Aksentijevich I, Kim HS, Ho J, Cruse G, Jung MY, Gilfillan AM, Metcalfe DD, Nelson C, O'Brien M, Wisch L, Stone K, Douek DC, Gandhi C, Wanderer AA, Lee H, Nelson SF, Shianna KV, Cirulli ET, Goldstein DB, Long EO, Moir S, Meffre E, Holland SM, Kastner DL, Katan M, Hoffman HM, Milner JD. Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. N Engl J Med. 2012 Jan 26;366(4):330-8.
Siegel AM, Heimall J, Freeman AF, Hsu AP, Brittain E, Brenchley JM, Douek DC, Fahle GH, Cohen JI, Holland SM, Milner JD. A critical role for STAT3 signaling in the development and maintenance of human T cell memory. Immunity. 2011 Nov 23;35(5):806-18.
Datta S, Milner JD. Altered T-cell receptor signaling in the pathogenesis of allergic disease. J Allergy Clin Immunol. 2011 Feb;127(2):351-4.
Milner JD, Fazilleau N, McHeyzer-Williams M, Paul WE. Cutting edge: lack of high affinity competition for peptide in polyclonal CD4+ responses unmasks IL-4 production. J Immunol. 2010 Jun 15;184(12):6569-73.
Milner JD, Brenchley JM, Laurence A, Freeman AF, Hill BJ, Elias KM, Kanno Y, Spalding C, Elloumi HZ, Paulson ML, Davis J, Hsu A, Asher AI, O’Shea J, Holland SM, Paul WE, Douek DC. Impaired T(H)17 differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature. 2008 Apr 10;452(7188):773-6.
Milner JD, Ward JM, Keane-Myers A, Paul WE. Lymphopenic mice reconstituted with limited repertoire T cells develop severe, multiorgan, Th2-associated inflammatory disease. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):576-81.
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Last Updated January 30, 2012