Thor A Wagner, MD
"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."
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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.-
Related Resources
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Award Name Award Description Awarded By Award Date NIH Loan Repayment Program for Pediatric Research 2009 - 2011 Young Scientist Scholarship XVIII HIV International Drug Resistance Workshop 2009 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 -
Manuscripts in Refereed Journals
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Reeves DB, Duke ER, Wagner TA, Palmer SE, Spivak AM, Schiffer JTA majority of HIV persistence during antiretroviral therapy is due to infected cell proliferation.
30446650 Nature communications, 2018 Nov 16 : 9(1)4811 PMCID:PMC6240116 -
Chahroudi A, Wagner TA, Persaud DCNS Persistence of HIV-1 in Children: the Untapped Reservoir.
30159813 Current HIV/AIDS reports, 2018 Oct. : 15(5)382-387 -
Hale M, Mesojednik T, Romano Ibarra GS, Sahni J, Bernard A, Sommer K, Scharenberg AM, Rawlings DJ, Wagner TAEngineering 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 LMH1N1 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 -
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 DJEfficient modification of CCR5 in primary human hematopoietic cells using a megaTAL nuclease and AAV donor template.
26424571 Science translational medicine, 2015 Sep 30 : 7(307)307ra156 PMCID:PMC4790757 -
Waghmare A, Wagner T, Andrews R, Smith S, Kuypers J, Boeckh M, Moss R, Englund JASuccessful 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 -
Wagner TA, McLaughlin S, Garg K, Cheung CY, Larsen BB, Styrchak S, Huang HC, Edlefsen PT, Mullins JI, Frenkel LMHIV 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 | McLaughlin S | Garg K | Cheung CY | Larsen BB | Styrchak S | Huang HC | Edlefsen PT | Mullins JI | Frenkel LMHIV 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, McKernan JL, Tobin NH, Tapia KA, Mullins JI, Frenkel LMAn 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 LMQuantification 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 LMMonitoring 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 -
Velu PP | Gravett CA | Roberts TK | Wagner TA | Zhang JS | Rubens CE | Gravett MG | Campbell H | Rudan IEpidemiology 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 -
Roberts T | Gravett CA | Velu PP | Theodoratou E | Wagner TA | Zhang JS | Campbell H | Rubens CE | Gravett MG | Rudan IEpidemiology and aetiology of maternal parasitic infections in low- and middle-income countries.
Journal of global health, 2011 Dec. : 1(2)189-200 PMCID:PMC3484768 -
Wagner T, Gravett C, Healy S, Soma V, Patterson J, Gravett M, Rubens CEmerging Biomarkers for the Diagnosis of Severe Neonatal Infections Applicable to Low Resource Settings
23198120 J Glob Health, 2011 : 1(2)210-223 PMCID:PMC3484779 -
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 WIAstrovirus encephalitis in boy with X-linked agammaglobulinemia.
Emerging infectious diseases, 2010 June : 16(6)918-25 PMCID:PMC4102142 -
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 GroupAssociation 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 -
Wagner TA, Kress CM, Beck I, Techapornroong M, Wittayapraparat P, Tansuphasawasdikul S, Jourdain G, Ngo-Giang-Huong N, Lallemant M, Frenkel LMDetection 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 -
Wagner TA, Tobin NH, McKernan JL, Xu M, Melvin AJ, Mohan KM, Learn GH, Mullins JI, Frenkel LMIncreased 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 -
Lin CH, Sloan DD, Dang CH, Wagner T, Cabrera AJ, Tobin NH, Frenkel LM, Jerome KRAssessment 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, Frenkel LMPotential 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, Soong G, Sokol S, Saiman L, Prince AEffects of azithromycin on clinical isolates of Pseudomonas aeruginosa from cystic fibrosis patients.
16100186 Chest, 2005 Aug. : 128(2)912-9
Book Chapters
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Smith J and Wagner TChapter 90: Immunization in Children Undergoing Dialysis. Nissenson and Fine’s Handbook of Dialysis Therapy, 5th edition, Elsevier
2016 Nov 9
Published Books, Videos, Software, etc.
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Application No.: PCT/US2015/024876PATENT: CCR5 DISRUPTION OF CELLS EXPRESSING ANTI-HIV CHIMERIC ANTIGEN RECEPTOR (CAR) DERIVED FROM BROADLY NEUTRALIZING ANTIBODIES
2015 Apr 8
Other Publications
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Wagner TAQuarter Century of Anti-HIV CAR T Cells.
29500712 Current HIV/AIDS reports, 2018 April : 15(2)147-154 PMCID:PMC5884727 -
Wagner TACombining Cell and Gene Therapy in an Effort to Eradicate HIV.
27905840 AIDS patient care and STDs, 2016 Dec. : 30(12)534-538 PMCID:PMC5144862 -
Wagner TA, Frenkel LMYet Another Reason to Treat HIV Infection. Editorial commentary
22308271 Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2012 April : 54(7)1010-2 -
Wagner T, Gravett C, Gravett M, Rubens, CA global health opportunity: the potential of multiplexed diagnostics in low resource settings. Viewpoint
J Glob Health, 2011 : 1(2)136-139 -
Wagner TA, Frenkel LMAntiretroviral treatment for HIV-infected infants exposed to nevirapine. Author reply
21156944 JAMA : the journal of the American Medical Association, 2010 Dec. : 304(23)2589; author reply 2589-90 -
Wagner T, Burns JLAnti-inflammatory properties of macrolides. Review
17195710 The Pediatric infectious disease journal, 2007 Jan. : 26(1)75-6 -
Wagner TA, Frenkel LMClinical Significance of HIV-1 Drug Resistance Mutations. Review
Lab Med, 2006 : 37554-561
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Presentations Title Event Location Date "Potential of CAR T Cells for Treating Infectious Diseases" (Lecture) CAR-TCR Summit, 9/2016 Boston, MA "HIV-Resistant CAR T cells in SHIV-Infected non-human primates" (Lecture) Strategies for an HIV Cure, 10/2018 Bethesda, MD "Dual HIVCAR+ non-human primate T cells with CRISPR-mediated CCR5 disruption" (Poster) Strategies for an HIV Cure, 10/2018 Bethesda, MD "∆CCR5 anti-HIV CAR T cells engraft and persist in SHIV-infected pig-tailed macaques" (Poster) CROI, 3/2018 Boston, MA "Chronic HIV Infection: what can we learn from cancer" (Lecture) Third Coast Center for AIDS Research, Northwestern University, 5/2017 Chicago, IL "An Update on Epstein-Barr Virus Infection and the Management of Lymphoproliferactive Disease” (Lecture) Pediatric Heart Transplant Summit, 9/2017 Seattle, WA "Reservoir ecology shows HIV persists on long-term ART due to cellular proliferation" (Lecture) The Conference on Cell & Gene Therapy for HIV Cure, 8/2017 Seattle, WA "Targeted killing of HIV infected cells using CCR5-disrupted anti-HIV-CAR T cells" (Lecture) American Society of Gene and Cell Therapy Annual Meeting, 5/2016 Washington, DC "Combining gene and cell therapy in an effort to eradicate HIV: Building a Bulletproof CAR" (Lecture) American Foundation for AIDS Research (amfAR) Think Tank, 6/2016 Portland, OR "MegaTAL-based methods of CCR5 disruption to protect anti-HIV CAR+ lymphocytes from HIV Infection" (Lecture) Conference on Cell and Gene Therapy for HIV Cure, 8/2015 Seattle, WA "MegaTAL Disruption of CCR5 to Protect Anti-HIV CAR+ Lymphocytes from HIV Infection" (Poster) American Society of Gene and Cell Therapy Annual Meeting, 5/2015 New Orleans, LA "Engineering HIV-resistant anti-HIV CAR T cells" (Lecture) Conference on Cell and Gene Therapy for HIV Cure, 8/2016 Seattle, WA "Proliferation of cells with HIV integration into cancer-associated genes contributes to the persistence of HIV in antiretroviral treated individuals" (Lecture) Lab Directors Meeting, 2014 IMPAACT Network Annual Meeting, 6/2014 Washington, DC "Anti-HIV CAR+ Lymphocytes Protected from HIV-Infection by CCR5 Disruption as a Strategy to Cure HIV" (Poster) International AIDS Society Towards an HIV Cure Symposium, 7/2015 Vancouver, Canada "Efficient Targeted Gene Modification in Primary Human Hematopoietic Cells Using Co-Delivery of Nuclease mRNA and AAV Donors" (Lecture) American Society of Gene and Cell Therapy Annual Meeting, 5/2015 New Orleans, LA "Engineering HIV-resistant anti-HIV CAR T cells" (Poster) Conference of Retroviruses and Opportunistic Infections, 2/2017 Seattle, WA "H1N1 Influenza Vaccination Does Not Appear to Alter HIV-1 DNA Reservoirs" (Poster) Pediatric Academic Societies, 4/2015 San Diego, CA "Treating HIV Like Cancer: Engineering CAR T-cells to Eradicate the Cellular Reservoir of HIV" (Lecture) UW CFAR New Faces Seminar, 5/2015 Seattle, WA "HIV/SHIV-Specific, CCR5-Edited CAR T-Cells Engraft and Persist in Acutely Infected Nonhuman Primates" (Poster) 35th Annual Symposium on Nonhuman Primate Models for AIDS, 8/2017 Madison, WI "Chronic HIV Infection: what can we learn from cancer" (Lecture) CHIMPs Rounds, British Columbia Children's Hospital, 3/2017 Vancouver, BC "Multiple identical proviral sequences with identical integration sites demonstrate proliferation of HIV infected cells during suppressive antiretroviral treatment" (Lecture) CURE TSG of the AIDS Clinical Trials Group, 7/2013 Teleconference -
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) Sep 1, 2016 - Nov 30, 2017 "Cell and Gene Therapy for HIV Cure" NIH/NIAID/NIDA/NIMH/NINDS, UM1 AI126623 (MPI: Jermone, Kiem) Jul 1, 2016 - Jun 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 Jul 1, 2015 - Jun 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 Mar 15, 2014 - Feb 28, 2019 Persistent HIV-1 Replication in the Respiratory Tract Despite Antiretroviral Treatment NIH/NIAID, K23 AI077357 Sep 1, 2008 - Nov 30, 2013
Overview
- Board Certification(s)
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Pediatric Infectious Diseases
Pediatrics
- Medical/Professional School
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Temple University School of Medicine, Philadelphia, PA
- Residency
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Children's Hospital of New York, New York, NY
- Fellowship
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Seattle Children's Hospital, Seattle, WA
- Clinical Interests
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General pediatric infectious diseases, pediatric HIV
Mechanism of persistent HIV infection despite effective treatment, improving HIV diagnostics for the low resource settings - Research Description
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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
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Infectious Disease