Medical College of Wisconsin
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John M. Routes MD

Chief, Professor

Institution: Medical College of Wisconsin
Department: Pediatrics
Division: Allergy

Member of the Cancer Center

Leadership Positions

  • Section Head, Allergy and Clinical Immunology
  • President, Clinical Immunology Society
  • Publications

  • Sarcoidosis and common variable immunodeficiency: similarities and differences. (Verbsky JW, Routes JM) Semin Respir Crit Care Med 2014 Jun;35(3):330-5 PMID 25007085
  • Characterization of Crohn disease in X-linked inhibitor of apoptosis-deficient male patients and female symptomatic carriers. (Aguilar C, Lenoir C, Lambert N, Bègue B, Brousse N, Canioni D, Berrebi D, Roy M, Gérart S, Chapel H, Schwerd T, Siproudhis L, Schäppi M, Al-Ahmari A, Mori M, Yamaide A, Galicier L, Neven B, Routes J, Uhlig HH, Koletzko S, Patel S, Kanegane H, Picard C, Fischer A, Bensussan NC, Ruemmele F, Hugot JP, Latour S) J Allergy Clin Immunol 2014 Nov;134(5):1131-41.e9 PMID 24942515
  • A172: Metaphyseal Chondrodysplasia, Ectodermal Dysplasia, Short Stature, Hypergammaglobulinemia, and Spontaneous Inflammation Without Infections in an Extended Family Due to Mutation in NFKB1A. (Oberle EJ, Verbsky JW, Routes J, Hintermeyer M, Worthey E, Dasu T, Bengtson C, Buzzell A) Arthritis Rheumatol 2014 Mar;66 Suppl 11:S224-5 PMID 24677928
  • ICON: the early diagnosis of congenital immunodeficiencies. (Routes J, Abinun M, Al-Herz W, Bustamante J, Condino-Neto A, De La Morena MT, Etzioni A, Gambineri E, Haddad E, Kobrynski L, Le Deist F, Nonoyama S, Oliveira JB, Perez E, Picard C, Rezaei N, Sleasman J, Sullivan KE, Torgerson T) J Clin Immunol 2014 May;34(4):398-424 PMID 24619621
  • Possible role of arginase-1 in concomitant tumor immunity. (Korrer MJ, Routes JM) PLoS One 2014;9(3):e91370 PMID 24614600
  • Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. (Medical Advisory Committee of the Immune Deficiency Foundation, Shearer WT, Fleisher TA, Buckley RH, Ballas Z, Ballow M, Blaese RM, Bonilla FA, Conley ME, Cunningham-Rundles C, Filipovich AH, Fuleihan R, Gelfand EW, Hernandez-Trujillo V, Holland SM, Hong R, Lederman HM, Malech HL, Miles S, Notarangelo LD, Ochs HD, Orange JS, Puck JM, Routes JM, Stiehm ER, Sullivan K, Torgerson T, Winkelstein J) J Allergy Clin Immunol 2014 Apr;133(4):961-6 PMID 24582311
  • Primary Immune Deficiency Treatment Consortium (PIDTC) report. (Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Pai SY, Ballard B, Bauer SC, Bleesing JJ, Boyle M, Brower A, Buckley RH, van der Burg M, Burroughs LM, Candotti F, Cant AJ, Chatila T, Cunningham-Rundles C, Dinauer MC, Dvorak CC, Filipovich AH, Fleisher TA, Bobby Gaspar H, Gungor T, Haddad E, Hovermale E, Huang F, Hurley A, Hurley M, Iyengar S, Kang EM, Logan BR, Long-Boyle JR, Malech HL, McGhee SA, Modell F, Modell V, Ochs HD, O'Reilly RJ, Parkman R, Rawlings DJ, Routes JM, Shearer WT, Small TN, Smith H, Sullivan KE, Szabolcs P, Thrasher A, Torgerson TR, Veys P, Weinberg K, Zuniga-Pflucker JC, workshop participants) J Allergy Clin Immunol 2014 Feb;133(2):335-47 PMID 24139498
  • Screening for severe combined immunodeficiency in neonates. (Kelly BT, Tam JS, Verbsky JW, Routes JM) Clin Epidemiol 2013;5:363-9 PMID 24068875
  • Common variable immunodeficiency. (Tam JS, Routes JM) Am J Rhinol Allergy 2013 Jul-Aug;27(4):260-5 PMID 23883805
  • Inflammatory signals direct expression of human IL12RB1 into multiple distinct isoforms. (Ford NR, Miller HE, Reeme AE, Waukau J, Bengtson C, Routes JM, Robinson RT) J Immunol 2012 Nov 1;189(9):4684-94 PMID 23024274
  • Use of combination chemotherapy for treatment of granulomatous and lymphocytic interstitial lung disease (GLILD) in patients with common variable immunodeficiency (CVID). (Chase NM, Verbsky JW, Hintermeyer MK, Waukau JK, Tomita-Mitchell A, Casper JT, Singh S, Shahir KS, Tisol WB, Nugent ML, Rao RN, Mackinnon AC, Goodman LR, Simpson PM, Routes JM) J Clin Immunol 2013 Jan;33(1):30-9 PMID 22930256
  • Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency. (Wasserman RL, Melamed I, Stein MR, Gupta S, Puck J, Engl W, Leibl H, McCoy B, Empson VG, Gelmont D, Schiff RI, IGSC, 10% with rHuPH20 Study Group) J Allergy Clin Immunol 2012 Oct;130(4):951-7.e11 PMID 22846381
  • The Wisconsin approach to newborn screening for severe combined immunodeficiency. (Verbsky J, Thakar M, Routes J) J Allergy Clin Immunol 2012 Mar;129(3):622-7 PMID 22244594
  • Newborn screening for SCID: three years of experience. (Chase NM, Verbsky JW, Routes JM) Ann N Y Acad Sci 2011 Nov;1238:99-105 PMID 22129057
  • Newborn screening for severe combined immunodeficiency; the Wisconsin experience (2008-2011). (Verbsky JW, Baker MW, Grossman WJ, Hintermeyer M, Dasu T, Bonacci B, Reddy S, Margolis D, Casper J, Gries M, Desantes K, Hoffman GL, Brokopp CD, Seroogy CM, Routes JM) J Clin Immunol 2012 Feb;32(1):82-8 PMID 22068910
  • Screening newborns for primary T-cell immunodeficiencies: consensus and controversy. (Accetta Pedersen DJ, Verbsky J, Routes JM) Expert Rev Clin Immunol 2011 Nov;7(6):761-8 PMID 22014017
  • Expert commentary: practical issues in newborn screening for severe combined immune deficiency (SCID). (Puck JM, Routes J, Filipovich AH, Sullivan K) J Clin Immunol 2012 Feb;32(1):36-8 PMID 22012274
  • Cause of death in neonates with inconclusive or abnormal T-cell receptor excision circle assays on newborn screening. (Accetta DJ, Brokopp CD, Baker MW, Verbsky J, Routes JM) J Clin Immunol 2011 Dec;31(6):962-7 PMID 21956495
  • Global study of primary immunodeficiency diseases (PI)--diagnosis, treatment, and economic impact: an updated report from the Jeffrey Modell Foundation. (Modell V, Gee B, Lewis DB, Orange JS, Roifman CM, Routes JM, Sorensen RU, Notarangelo LD, Modell F) Immunol Res 2011 Oct;51(1):61-70 PMID 21935653
  • Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. (Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB, Decker B, Serpe JM, Dasu T, Tschannen MR, Veith RL, Basehore MJ, Broeckel U, Tomita-Mitchell A, Arca MJ, Casper JT, Margolis DA, Bick DP, Hessner MJ, Routes JM, Verbsky JW, Jacob HJ, Dimmock DP) Genet Med 2011 Mar;13(3):255-62 PMID 21173700
  • Human phagocyte defect caused by a Rac2 mutation detected by means of neonatal screening for T-cell lymphopenia. (Accetta D, Syverson G, Bonacci B, Reddy S, Bengtson C, Surfus J, Harbeck R, Huttenlocher A, Grossman W, Routes J, Verbsky J) J Allergy Clin Immunol 2011 Feb;127(2):535-538.e1-2 PMID 21167572
  • Newborn screening for T-cell deficiency. (Chase NM, Verbsky JW, Routes JM) Curr Opin Allergy Clin Immunol 2010 Dec;10(6):521-5 PMID 20864885
  • Multiplexed quantitative real-time PCR to detect 22q11.2 deletion in patients with congenital heart disease. (Tomita-Mitchell A, Mahnke DK, Larson JM, Ghanta S, Feng Y, Simpson PM, Broeckel U, Duffy K, Tweddell JS, Grossman WJ, Routes JM, Mitchell ME) Physiol Genomics 2010 Sep;42A(1):52-60 PMID 20551144
  • Implementing routine testing for severe combined immunodeficiency within Wisconsin's newborn screening program. (Baker MW, Laessig RH, Katcher ML, Routes JM, Grossman WJ, Verbsky J, Kurtycz DF, Brokopp CD) Public Health Rep 2010 May-Jun;125 Suppl 2:88-95 PMID 20518449
  • Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. (Griffith LM, Cowan MJ, Notarangelo LD, Puck JM, Buckley RH, Candotti F, Conley ME, Fleisher TA, Gaspar HB, Kohn DB, Ochs HD, O'Reilly RJ, Rizzo JD, Roifman CM, Small TN, Shearer WT, Workshop Participants) J Allergy Clin Immunol 2009 Dec;124(6):1152-60.e12 PMID 20004776
  • Statewide newborn screening for severe T-cell lymphopenia. (Routes JM, Grossman WJ, Verbsky J, Laessig RH, Hoffman GL, Brokopp CD, Baker MW) JAMA 2009 Dec 9;302(22):2465-70 PMID 19996402
  • Development of a routine newborn screening protocol for severe combined immunodeficiency. (Baker MW, Grossman WJ, Laessig RH, Hoffman GL, Brokopp CD, Kurtycz DF, Cogley MF, Litsheim TJ, Katcher ML, Routes JM) J Allergy Clin Immunol 2009 Sep;124(3):522-7 PMID 19482345
  • E1A oncogene enhancement of caspase-2-mediated mitochondrial injury sensitizes cells to macrophage nitric oxide-induced apoptosis. (Radke JR, Siddiqui ZK, Miura TA, Routes JM, Cook JL) J Immunol 2008 Jun 15;180(12):8272-9 PMID 18523293
  • Immunodeficiency overview. (Morimoto Y, Routes JM) Prim Care 2008 Mar;35(1):159-73, viii PMID 18206723
  • Measurement of natural-killer cell lytic activity of adenovirus-infected or adenovirus-transformed cells. (Routes JM) Methods Mol Med 2007;131:213-9 PMID 17656785
  • Pulmonary infection with Mycobacterium neoaurum identified by 16S ribosomal DNA sequence. (Morimoto Y, Chan ED, Heifets L, Routes JM) J Infect 2007 Apr;54(4):e227-31 PMID 17306883
  • The interaction of adenovirus E1A with p300 family members modulates cellular gene expression to reduce tumorigenicity. (Miura TA, Cook JL, Potter TA, Ryan S, Routes JM) J Cell Biochem 2007 Mar 1;100(4):929-40 PMID 17063489
  • Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection. (Routes JM, Ryan S, Morris K, Takaki R, Cerwenka A, Lanier LL) J Exp Med 2005 Dec 5;202(11):1477-82 PMID 16314433
  • Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. (Wheat WH, Cool CD, Morimoto Y, Rai PR, Kirkpatrick CH, Lindenbaum BA, Bates CA, Ellison MC, Serls AE, Brown KK, Routes JM) J Exp Med 2005 Aug 15;202(4):479-84 PMID 16103407
  • Granulomatous disease in common variable immunodeficiency. (Morimoto Y, Routes JM) Curr Allergy Asthma Rep 2005 Sep;5(5):370-5 PMID 16091208
  • Practice parameter for the diagnosis and management of primary immunodeficiency. (Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, Kobrynski LJ, Levinson AI, Mazer B, Nelson RP Jr, Orange JS, Routes JM, Shearer WT, Sorensen RU, American Academy of Allergy, Asthma and Immunology, American College of Allergy, Asthma and Immunology, Joint Council of Allergy, Asthma and Immunology) Ann Allergy Asthma Immunol 2005 May;94(5 Suppl 1):S1-63 PMID 15945566
  • Uncommon conundrum in common variable immunodeficiency. (Cunningham-Rundles C, Routes JM, Hostoffer R, Sullivan KE) Clin Immunol 2005 Sep;116(3):208-10 PMID 15905130
  • Adenovirus E1A gene-induced tumor cell rejection through cellular sensitization to immune and nonimmune apoptotic injuries. (Cook JL, Routes JM) Front Biosci 2005;10:1396-414 PMID 15769634
  • Pre-event smallpox vaccination and postevent exposure and disease: a report of the Joint Task Force on Smallpox Vaccination for Allergists. (Ein D, Gruchalla R, Baker JR, Bellanti JA, Engler RA, Jones JF, Martin BL, Routes JM, Task Force on Smallpox Vaccination for Allergists) Ann Allergy Asthma Immunol 2005 Jan;94(1):4-7 PMID 15702806
  • Macrophages kill human papillomavirus type 16 E6-expressing tumor cells by tumor necrosis factor alpha- and nitric oxide-dependent mechanisms. (Routes JM, Morris K, Ellison MC, Ryan S) J Virol 2005 Jan;79(1):116-23 PMID 15596807
  • Dose dependence and time course of the immunologic response to administration of standardized cat allergen extract. (Nanda A, O'connor M, Anand M, Dreskin SC, Zhang L, Hines B, Lane D, Wheat W, Routes JM, Sawyer R, Rosenwasser LJ, Nelson HS) J Allergy Clin Immunol 2004 Dec;114(6):1339-44 PMID 15577832
  • Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. (Bates CA, Ellison MC, Lynch DA, Cool CD, Brown KK, Routes JM) J Allergy Clin Immunol 2004 Aug;114(2):415-21 PMID 15316526
  • Expression of an E1A/E7 chimeric protein sensitizes tumor cells to killing by activated macrophages but not NK cells. (Miura TA, Li H, Morris K, Ryan S, Hembre K, Cook JL, Routes JM) J Virol 2004 May;78(9):4646-54 PMID 15078947
  • Expression of human herpesvirus 8 in primary pulmonary hypertension. (Cool CD, Rai PR, Yeager ME, Hernandez-Saavedra D, Serls AE, Bull TM, Geraci MW, Brown KK, Routes JM, Tuder RM, Voelkel NF) N Engl J Med 2003 Sep 18;349(12):1113-22 PMID 13679525
  • E1A oncogene-induced sensitization of human tumor cells to innate immune defenses and chemotherapy-induced apoptosis in vitro and in vivo. (Cook JL, Miura TA, Iklé DN, Lewis AM Jr, Routes JM) Cancer Res 2003 Jun 15;63(12):3435-43 PMID 12810682
  • Adenovirus E1A, not human papillomavirus E7, sensitizes tumor cells to lysis by macrophages through nitric oxide- and TNF-alpha-dependent mechanisms despite up-regulation of 70-kDa heat shock protein. (Miura TA, Morris K, Ryan S, Cook JL, Routes JM) J Immunol 2003 Apr 15;170(8):4119-26 PMID 12682242
  • Role of the innate immune response in determining the tumorigenicity of neoplastic cells. (Cook JL, Routes JM) Dev Biol (Basel) 2001;106:99-107; discussion 107-8, 143-60 PMID 11761273
  • MHC class I molecules on adenovirus E1A-expressing tumor cells inhibit NK cell killing but not NK cell-mediated tumor rejection. (Routes JM, Ryan JC, Ryan S, Nakamura M) Int Immunol 2001 Oct;13(10):1301-7 PMID 11581175
  • CREB (cAMP response element binding protein) and C/EBPalpha (CCAAT/enhancer binding protein) are required for the superstimulation of phosphoenolpyruvate carboxykinase gene transcription by adenoviral E1a and cAMP. (Routes JM, Colton LA, Ryan S, Klemm DJ) Biochem J 2000 Dec 1;352 Pt 2:335-42 PMID 11085926
  • Dissimilar immunogenicities of human papillomavirus E7 and adenovirus E1A proteins influence primary tumor development. (Routes JM, Ryan S, Li H, Steinke J, Cook JL) Virology 2000 Nov 10;277(1):48-57 PMID 11062035
  • Adenovirus E1A oncogene expression in tumor cells enhances killing by TNF-related apoptosis-inducing ligand (TRAIL). (Routes JM, Ryan S, Clase A, Miura T, Kuhl A, Potter TA, Cook JL) J Immunol 2000 Oct 15;165(8):4522-7 PMID 11035092
  • Lack of correlation between Chlamydia pneumoniae antibody titers and adult-onset asthma. (Routes JM, Nelson HS, Noda JA, Simon FT) J Allergy Clin Immunol 2000 Feb;105(2 Pt 1):391-2 PMID 10669864
  • E1A oncogene induction of cellular susceptibility to killing by cytolytic lymphocytes through target cell sensitization to apoptotic injury. (Cook JL, Routes BA, Walker TA, Colvin KL, Routes JM) Exp Cell Res 1999 Sep 15;251(2):414-23 PMID 10471326
  • Noninfectious immunologic disorders in adults. (Bensch G, Routes JM) Chest Surg Clin N Am 1999 Feb;9(1):113-24, ix PMID 10079983
  • Hypersensitivity pneumonitis in a patient with hypogammaglobulinemia. (Schkade PA, Routes JM) J Allergy Clin Immunol 1996 Sep;98(3):710-2 PMID 8828552
  • Adenovirus E1A proteins regulate phosphoenolpyruvate carboxykinase gene transcription through multiple mechanisms. (Klemm DJ, Colton LA, Ryan S, Routes JM) J Biol Chem 1996 Apr 5;271(14):8082-8 PMID 8626493
  • Inhibition of IFN-stimulated gene expression and IFN induction of cytolytic resistance to natural killer cell lysis correlate with E1A-p300 binding. (Routes JM, Li H, Bayley ST, Ryan S, Klemm DJ) J Immunol 1996 Feb 1;156(3):1055-61 PMID 8557979
  • Oncogenicity of human papillomavirus- or adenovirus-transformed cells correlates with resistance to lysis by natural killer cells. (Routes JM, Ryan S) J Virol 1995 Dec;69(12):7639-47 PMID 7494272
  • E1A gene expression induces susceptibility to killing by NK cells following immortalization but not adenovirus infection of human cells. (Routes JM, Cook JL) Virology 1995 Jul 10;210(2):421-8 PMID 7618277
  • Oral desensitization to rifampin and ethambutol in mycobacterial disease. (Matz J, Borish LC, Routes JM, Rosenwasser LJ) Am J Respir Crit Care Med 1994 Mar;149(3 Pt 1):815-7 PMID 8118654
  • Activities of superoxide dismutases and NADPH oxidase in neutrophils obtained from asthmatic and normal donors. (Joseph BZ, Routes JM, Borish L) Inflammation 1993 Jun;17(3):361-70 PMID 8392494
  • Endogenous expression of E1A in human cells enhances the effect of adenovirus E3 on class I major histocompatibility complex antigen expression. (Routes JM, Metz BA, Cook JL) J Virol 1993 Jun;67(6):3176-81 PMID 8497046
  • Adenovirus E1A inhibits IFN-induced resistance to cytolysis by natural killer cells. (Routes JM) J Immunol 1993 May 15;150(10):4315-22 PMID 7683316
  • Diffuse pulmonary infiltrates in hypogammaglobulinemia. (Matz J, Routes JM, Borish LC) Ann Allergy 1992 Dec;69(6):485-90 PMID 1471779
  • IFN increases class I MHC antigen expression on adenovirus-infected human cells without inducing resistance to natural killer cell killing. (Routes JM) J Immunol 1992 Oct 1;149(7):2372-7 PMID 1382100
  • Anti-adenovirus type 5 cytotoxic T lymphocytes: immunodominant epitopes are encoded by the E1A gene. (Routes JM, Bellgrau D, McGrory WJ, Bautista DS, Graham FL, Cook JL) J Virol 1991 Mar;65(3):1450-7 PMID 1704928
  • Resistance of human cells to the adenovirus E3 effect on class I MHC antigen expression. Implications for antiviral immunity. (Routes JM, Cook JL) J Immunol 1990 Apr 1;144(7):2763-70 PMID 2156934
  • Adenovirus persistence in man. Defective E1A gene product targeting of infected cells for elimination by natural killer cells. (Routes JM, Cook JL) J Immunol 1989 Jun 1;142(11):4022-6 PMID 2541204
  • Corticosteroids in inflammatory bowel disease. A review. (Routes J, Claman HN) J Clin Gastroenterol 1987 Oct;9(5):529-35 PMID 3316373
  • Studies on nicotinic acetylcholine receptors in mammalian brain. Preliminary characterization of membrane-bound alpha-bungarotoxin receptors in rat cerebral cortex. (McQuarrie C, Salvaterra PM, De Blas A, Routes J, Mahler HR) J Biol Chem 1976 Oct 25;251(20):6335-9 PMID 977573
  • Grants and Awards

  • Anti-tumorigenic Activity of Adenovirus E1A (#9204767 08/14/2007 - 07/31/2013) Sponsor: NIH Cancer Institute
  • Epidemiology & Inpatient Management of Patients Hospitalized for Acute Asthma: 37th Multicenter Airway Research Collaboration (MARC-37) Study (#9306775 08/14/2014 - 10/13/2014) Sponsor: Massachusetts General Hospital
  • A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Brodalumab in Subjects With Inadequately Controlled Asthma and High Bronchodilator Reversibility (#9306246 06/03/2013 - 06/02/2015) Sponsor: Amgen Inc.
  • A Clinical Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) for the Evaluation of Efficacy, Safety, Tolerability, and Pharmacokinetics in Subjects with Primary Immunodeficiency Diseases (#9306104 05/17/2013 - 05/16/2016) Sponsor: Parexel International, LLC
  • GLILD in CVID (#9208689 07/10/2014 - 06/30/2015) Sponsor: NIH Allergy and Infectious Diseases
  • Autoantibody Production and Regulatory T Cells (#9207663 08/01/2012 - 01/31/2015) Sponsor: NIH Allergy and Infectious Diseases