Profile

Thor A. Wagner, MD

Thor A. Wagner, MD

Infectious Disease

On staff since July 2008

Academic Title: Assistant Professor

Research Center: Center for Global Infectious Disease Research

"My research is inspired by patients that I meet and directed at the problems that they face. There are exciting opportunities to adapt current biotechnology to help our patients' needs, and it's great motivation to know that the research we do has the potential to directly benefit our patients."

  • Thor Wagner, MD: Assistant Professor of Pediatric Infectious Diseases. Dr. Wagner's research is focused on pediatric HIV infection, which accounts for 15% of all HIV deaths.

    My primary interest is understanding chronic HIV infection during antiretroviral therapy. Specifically, why doesn't antiretroviral therapy eradicate HIV infection? Is there ongoing viral replication? Is there proliferation of cells with viable proviral HIV? Can we identify the remaining infected cells? Is immune tolerance to HIV a barrier to curing HIV? Answers to these questions should help design new treatment strategies more likely to cure HIV.
    My other research interest is improving infectious disease diagnostics in low resource settings. Specifically, I am working to develop a point-of-care diagnostic test for infant HIV. Currently there is no simple test to diagnose infants with HIV, and 50% of HIV-infected children die before they can be diagnosed. To accomplish this we are utilizing state-of-the-art monoclonal antibody screening technology to optimize the sensitivity of immunoassays to detect HIV antigens.

    • Unraveling How HIV Survives

      Seattle Children’s researchers show that one way HIV survives antiretroviral treatment is by disrupting genes that control cell proliferation. ... cont.

  • Award Name Award Description Awarded By Award Date
    Young Scientist Scholarship XVIII HIV International Drug Resistance Workshop 2009
    NIH Loan Repayment Program for Pediatric Research 2009 - 2011
    Postdoctoral Fellowship in Tropical Infectious Disease Burroughs Wellcome Fund, American Society of Tropical Medicine and Hygiene 2008 - 2010
    Young Investigator Award 15th Conf. on Retroviruses and Opportunistic Infections 2008
    Department of Pediatrics Fellows' Research Day Award Seattle Children's Research Institute 2007
    • Hale M, Mesojednik T, Romano Ibarra GS, Sahni J, Bernard A, Sommer K, Scharenberg AM, Rawlings DJ, Wagner TA
      Engineering HIV-Resistant, Anti-HIV Chimeric Antigen Receptor T Cells.
      28143740 Molecular therapy : the journal of the American Society of Gene Therapy , 2017 Mar. 1 : 25(3)570-579 PMCID: PMC5363191
    • Wagner TA, Huang HC, Salyer CE, Richardson KM, Weinberg A, Nachman S, Frenkel LM
      H1N1 influenza vaccination in HIV-infected women on effective antiretroviral treatment did not induce measurable antigen-driven proliferation of the HIV-1 proviral reservoir.
      28193244 AIDS research and therapy , 2017 Feb. 13 : 14(1)7 PMCID: PMC5307755
    • Wagner TA
      Combining Cell and Gene Therapy in an Effort to Eradicate HIV.
      27905840 AIDS patient care and STDs , 2016 Dec. : 30(12)534-538 PMCID: PMC5144862
    • Smith J and Wagner T
      Chapter 90: Immunization in Children Undergoing Dialysis. Nissenson and Fine’s Handbook of Dialysis Therapy, 5th edition, Elsevier
    • Sather BD, Romano Ibarra GS, Sommer K, Curinga G, Hale M, Khan IF, Singh S, Song Y, Gwiazda K, Sahni J, Jarjour J, Astrakhan A, Wagner TA, Scharenberg AM, Rawlings DJ
      Efficient modification of CCR5 in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template.
      26424571 Science translational medicine , 2015 Sept. 30 : 7(307)307ra156 PMCID: PMC4790757
    • Waghmare A, Wagner T, Andrews R, Smith S, Kuypers J, Boeckh M, Moss R, Englund JA
      Successful Treatment of Parainfluenza Virus Respiratory Tract Infection With DAS181 in 4 Immunocompromised Children.
      26185620 Journal of the Pediatric Infectious Diseases Society , 2015 June : 4(2)114-8 PMCID: PMC4501511
    • Application No.: PCT/US2015/024876
      PATENT: CCR5 DISRUPTION OF CELLS EXPRESSING ANTI-HIV CHIMERIC ANTIGEN RECEPTOR (CAR) DERIVED FROM BROADLY NEUTRALIZING ANTIBODIES
    • Wagner TA | McLaughlin S | Garg K | Cheung CY | Larsen BB | Styrchak S | Huang HC | Edlefsen PT | Mullins JI | Frenkel LM
      HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection.
      Science (New York, N.Y.) , 2014 Aug. 1 : 345(6196)570-3 PMCID: PMC4230336
    • Wagner TA, McLaughlin S, Garg K, Cheung CY, Larsen BB, Styrchak S, Huang HC, Edlefsen PT, Mullins JI, Frenkel LM
      HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection.
      25011556 Science (New York, N.Y.) , 2014 Aug. 1 : 345(6196)570-3 PMCID: PMC4230336
    • Wagner TA, McKernan JL, Tobin NH, Tapia KA, Mullins JI, Frenkel LM
      An increasing proportion of monotypic HIV-1 DNA sequences during antiretroviral treatment suggests proliferation of HIV-infected cells.
      23175380 Journal of virology , 2013 Feb. : 87(3)1770-8 PMCID: PMC3554159
    • Wagner TA, Lin CH, Tobin NH, Côté HC, Sloan DD, Jerome KR, Frenkel LM
      Quantification of mitochondrial toxicity in HIV-infected individuals by quantitative PCR compared to flow cytometry.
      23044657 Cytometry. Part B, Clinical Cytometry , 2013 Jan. : 84(1)55-8 PMCID: PMC3966180
    • Beck IA, Jang M, McKernan-Mullin J, Bull M, Wagner T, Huang S, Song LY, Nachman S, Krogstad P, Eshleman SH, Wiznia A, Frenkel LM
      Monitoring of HIV type 1 DNA load and drug resistance in peripheral blood mononuclear cells during suppressive antiretroviral therapy does not predict virologic failure.
      22081867 AIDS research and human retroviruses , 2012 Aug. : 28(8)780-8 PMCID: PMC3399556
    • Wagner TA, Frenkel LM
      Yet Another Reason to Treat HIV Infection.
      22308271 Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2012 Apr, : 54(7)1010-2
    • Roberts T | Gravett CA | Velu PP | Theodoratou E | Wagner TA | Zhang JS | Campbell H | Rubens CE | Gravett MG | Rudan I
      Epidemiology and aetiology of maternal parasitic infections in low- and middle-income countries.
      Journal of global health , 2011 Dec. : 1(2)189-200 PMCID: PMC3484768
    • Velu PP | Gravett CA | Roberts TK | Wagner TA | Zhang JS | Rubens CE | Gravett MG | Campbell H | Rudan I
      Epidemiology and aetiology of maternal bacterial and viral infections in low- and middle-income countries.
      Journal of global health , 2011 Dec. : 1(2)171-88 PMCID: PMC3484781
    • Wagner T, Gravett C, Healy S, Soma V, Patterson J, Gravett M, Rubens C
      Emerging Biomarkers for the Diagnosis of Severe Neonatal Infections Applicable to Low Resource Settings
      23198120 J Glob Health , 2011 : 1(2)210-223 PMCID: PMC3484779
    • Wagner T, Gravett C, Gravett M, Rubens, C
      A global health opportunity: the potential of multiplexed diagnostics in low resource settings
      J Glob Health , 2011 : 1(2)136-139
    • Wagner TA, Frenkel LM
      Antiretroviral treatment for HIV-infected infants exposed to nevirapine.
      21156944 JAMA : the journal of the American Medical Association , 2010 Dec. : 304(23)2589; author reply 2589-90
    • Quan PL | Wagner TA | Briese T | Torgerson TR | Hornig M | Tashmukhamedova A | Firth C | Palacios G | Baisre-De-Leon A | Paddock CD | Hutchison SK | Egholm M | Zaki SR | Goldman JE | Ochs HD | Lipkin WI
      Astrovirus encephalitis in boy with X-linked agammaglobulinemia.
      Emerging infectious diseases , 2010 June : 16(6)918-25 PMCID: PMC4102142
    • Wagner TA, Kress CM, Beck I, Techapornroong M, Wittayapraparat P, Tansuphasawasdikul S, Jourdain G, Ngo-Giang-Huong N, Lallemant M, Frenkel LM
      Detection of HIV-1 drug resistance in women following administration of a single dose of nevirapine: comparison of plasma RNA to cellular DNA by consensus sequencing and by oligonucleotide ligation assay.
      20181911 Journal of clinical microbiology , 2010 May : 48(5)1555-61 PMCID: PMC2863880
    • Jourdain G, Wagner TA, Ngo-Giang-Huong N, Sirirungsi W, Klinbuayaem V, Fregonese F, Nantasen I, Techapornroong M, Halue G, Nilmanat A, Wittayapraparat P, Chalermpolprapa V, Pathipvanich P, Yuthavisuthi P, Frenkel LM, Lallemant M, Program for HIV Prevention and Treatment (PHPT) Study Group
      Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure.
      20377404 Clinical infectious diseases : an official publication of the Infectious Diseases Society of America , 2010 May : 50(10)1397-404 PMCID: PMC2856716
    • Lin CH, Sloan DD, Dang CH, Wagner T, Cabrera AJ, Tobin NH, Frenkel LM, Jerome KR
      Assessment of mitochondrial toxicity by analysis of mitochondrial protein expression in mononuclear cells.
      18823003 Cytometry. Part B, Clinical cytometry , 2009 May : 76(3)181-90
    • Wagner TA, Tobin NH, McKernan JL, Xu M, Melvin AJ, Mohan KM, Learn GH, Mullins JI, Frenkel LM
      Increased mutations in Env and Pol suggest greater HIV-1 replication in sputum-derived viruses compared with blood-derived viruses.
      19349849 AIDS (London, England) , 2009 May : 23(8)923-8 PMCID: PMC2677633
    • Wagner TA, Frenkel LM
      Potential limitation of CCR5 antagonists: drug resistance more often linked to CXCR4-utilizing than to CCR5-utilizing HIV-1.
      18981780 AIDS (London, England) , 2008 Nov. : 22(17)2393-5 PMCID: PMC2585823
    • Wagner T, Burns JL
      Anti-inflammatory properties of macrolides.
      17195710 The Pediatric infectious disease journal , 2007 Jan. : 26(1)75-6
    • Wagner TA, Frenkel LM
      Clinical Significance of HIV-1 Drug Resistance Mutations
      Lab Med , 2006 : 37554-561
    • Wagner T, Soong G, Sokol S, Saiman L, Prince A
      Effects of azithromycin on clinical isolates of Pseudomonas aeruginosa from cystic fibrosis patients.
      16100186 Chest , 2005 Aug. : 128(2)912-9

  • Presentations Title Event Location Date
    "Chronic HIV Infection: what can we learn from cancer." CHIMPs Rounds (Childrens Hospital Infection/Immunology and Microbiology Program). British Columbia Childrens Hospital Vancouver, BC 2017
    "Chronic HIV Infection: what can we learn from cancer." Seminar, Third Coast Center for AIDS Research, at Northwestern University Chicago, IL 2017
    "Combining gene and cell therapy in an effort to eradicate HIV: Building a Bulletproof CAR." American Foundation for AIDS Research (amfAR) Think Tank; Gene therapy strategies to eradicate HIV" Portland, OR 2016
    "Engineering HIV-resistant anti-HIV CAR T cells." Conference on Cell and Gene Therapy for HIV Cure Seattle, WA 2016
    "Potential of CAR T Cells for Treating Infectious Diseases." CAR-TCR Summit 2016 Boston, MA 2016
    1. "Treating HIV Like Cancer: Engineering CAR T-cells to Eradicate the Cellular Reservoir of HIV." UW CFAR New Faces Seminar Seattle, WA 2015
    "MegaTAL-based methods of CCR5 disruption to protect anti-HIV CAR+ lymphocytes from HIV Infection." Conference on Cell and Gene Therapy for HIV Cure Seattle, WA 2015
    "Proliferation of cells with HIV integration into cancer-associated genes contributes to the persistence of HIV in antiretroviral treated individuals." Lab Directors Meeting. 2014 IMPAACT Network Annual Meeting Washington, DC 2014
    "Multiple identical proviral sequences with identical integration sites demonstrate proliferation of HIV infected cells during suppressive antiretroviral treatment." HIV Reservoirs and Viral Eradication Transformative Science Group (Cure TSG) of the AIDS Clinical Trials Group Teleconference 2013
  • Grant Title Grantor Amount Award Date
    "Adoptive transfer of genetically protected and genetically modified defined populations of CAR T cells as a modality to achieve HIV-1 Cure" Gilead (PI: Corey) Jan. 1, 2017 - Dec. 31, 2019
    LOC-IMPAACT Leadership Group NIH/NIAID, UM1 AI068632 (PI: Nachman) Sept. 1, 2016 - Nov. 30, 2017
    "Cell and Gene Therapy for HIV Cure" NIH/NIAID/NIDA/NIMH/NINDS, UM1 AI126623 (MPI: Jermone, Kiem) July 1, 2016 - June 30, 2021
    Engineering T-cells with optimized anti-HIV chimeric antigen receptors and CCR5 disruption as a strategy to target HIV-infected cells NIH, R01 AI118500 $250,000 annual direct costs July 1, 2015 - June 30, 2020
    Optimizing potency of anti-HIV chimeric antigen receptors (CAR), CFAR Supplement NIH Oct. 1, 2014 - May 31, 2016
    Mechanisms of Formation and Persistence of Active HIV Reservoirs - R01 AI111806 (PI: Mullins) NIH $. $10,720 subcontract annual direct costs March 15, 2014 - Feb. 28, 2019
    Persistent HIV-1 Replication in the Respiratory Tract Despite Antiretroviral Treatment NIH/NIAID, K23 AI077357 Sept. 1, 2008 - Nov. 30, 2013

Overview

Board Certification(s)

Pediatrics
Pediatric Infectious Diseases

Medical/Professional School

Temple University School of Medicine, Philadelphia

Residency

Pediatrics, Children's Hospital of New York, CHN-517, New York

Fellowship

Infectious Disease, Seattle Children's Hospital, Seattle

Clinical Interests

General pediatric infectious diseases, pediatric HIV Mechanism of persistent HIV infection despite effective treatment, improving HIV diagnostics for the low resource settings

Research Description

My research is focused on pediatric HIV infection, which accounts for 15percent of all HIV deaths.

My primary interest is understanding chronic HIV infection during antiretroviral therapy. Specifically, why doesn't antiretroviral therapy eradicate HIV infection? Is there ongoing viral replication? Is there proliferation of cells with viable proviral HIV? Can we identify the remaining infected cells? Is immune tolerance to HIV a barrier to curing HIV? Answers to these questions should help design new treatment strategies more likely to cure HIV.

My other research interest is improving infectious disease diagnostics in low resource settings. Specifically, I am working to develop a point-of-care diagnostic test for infant HIV. Currently there is no simple test to diagnose infants with HIV, and 50percent of HIV-infected children die before they can be diagnosed. To accomplish this we are utilizing state-of-the-art monoclonal antibody screening technology to optimize the sensitivity of immunoassays to detect HIV antigens.

Research Focus Area

Infectious Disease