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Diane Bolton, Ph.D.

Chief, Animal Models and Pathogenesis

Dr. Diane Bolton received her Ph.D. from the NIH-Johns Hopkins University cooperative graduate program in 2006. She completed her postdoctoral fellowship on mucosal vaccination against pathogens such as HIV and tuberculosis, with a focus on T cell immunity, with Dr. Mario Roederer at NIH’s Vaccine Research Center in Bethesda, MD.

Research

Dr. Bolton’s interests focus on immune responses to vaccination and mechanisms of viral persistence during HIV/SIV infection. Her team explores the adaptive immune responses to prophylactic and therapeutic vaccine regimens to elucidate cellular and humoral correlates of protection.  Emphasis is placed on pre-clinical nonhuman primate animal models as well as clinical trials.

Persistence of HIV-1 reservoirs represents the primary barrier to curing HIV-1 infection. Cure strategies aiming to eliminate infected cell reservoirs are hampered by a poor understanding of host cells harboring virus in vivo, including biomarkers that definitively distinguish them.  The Bolton Lab probes clinical and pre-clinical specimens for infected cells by state-of-the-art molecular analyses to address questions regarding: 1) infected cell burden across anatomical compartments and infection stages; and 2) novel host factors involved in viral replication and persistence. These studies inform preventative vaccines and therapeutic curative interventions.  


Selected Publications

  1. Om K, Paquin-Proulx D, Montero M, Peachman K, Shen X, Wieczorek L, Beck Z, Weiner JA, Kim D, Li Y, Mdluli T, Shubin Z, Bryant C, Sharma V, Tokarev A, Dawson P, White Y, Appelbe O, Klatt NR, Tovanabutra S, Estes JD, Matyas GR, Ferrari G, Alving CR, Tomaras GD, Ackerman ME, Michael NL, Robb ML, Polonis V, Rolland M, Eller MA, Rao M, Bolton DL. Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge. PLoS Pathog. 2020 Sep;16(9):e1008764. doi: 10.1371/journal.ppat.1008764. eCollection 2020 Sep. PubMed PMID: 32881968.
  2. Sharma V, Bryant C, Montero M, Creegan M, Slike B, Krebs SJ, Ratto-Kim S, Valcour V, Sithinamsuwan P, Chalermchai T, Eller MA, Bolton DL. Monocyte and CD4+ T-cell antiviral and innate responses associated with HIV-1 inflammation and cognitive impairment. AIDS. 2020 Jul 15;34(9):1289-1301. doi: 10.1097/QAD.0000000000002537. PubMed PMID: 32598115.
  3. Tokarev A, McKinnon LR, Pagliuzza A, Sivro A, Omole TE, Kroon E, Chomchey N, Phanuphak N, Schuetz A, Robb ML, Eller MA, Ananworanich J, Chomont N, Bolton DL. Preferential infection of α4β7+ memory CD4+ T cells during early acute HIV-1 infection. Clin Infect Dis. 2020 Apr 29;. doi: 10.1093/cid/ciaa497. [Epub ahead of print] PubMed PMID: 32348459.
  4. Chattopadhyay PK, Roederer M, Bolton DL. A deadly dance: the choreography of host-pathogen interactions, as revealed by single-cell technologies. Nat Commun. 2018 Nov 6;9(1):4638. doi: 10.1038/s41467-018-06214-0. Review. PubMed PMID: 30401874; PubMed Central PMCID: PMC6219517.
  5. Tokarev A, Creegan M, Eller MA, Roederer M, Bolton DL. Single-cell Quantitation of mRNA and Surface Protein Expression in Simian Immunodeficiency Virus-infected CD4+ T Cells Isolated from Rhesus macaques. J Vis Exp. 2018 Sep 25;(139). doi: 10.3791/57776. PubMed PMID: 30320741; PubMed Central PMCID: PMC6235275.
  6. Bolton DL, McGinnis K, Finak G, Chattopadhyay P, Gottardo R, Roederer M. Combined single-cell quantitation of host and SIV genes and proteins ex vivo reveals host-pathogen interactions in individual cells. PLoS Pathog. 2017 Jun;13(6):e1006445. doi: 10.1371/journal.ppat.1006445. eCollection 2017 Jun. PubMed PMID: 28654687; PubMed Central PMCID: PMC5507340.
  7. Bolton DL, Song K, Tomaras GD, Rao S, Roederer M. Unique cellular and humoral immunogenicity profiles generated by aerosol, intranasal, or parenteral vaccination in rhesus macaques. Vaccine. 2017 Jan 23;35(4):639-646. doi: 10.1016/j.vaccine.2016.12.008. Epub 2016 Dec 29. PubMed PMID: 28041780; PubMed Central PMCID: PMC5241230.
  8. Bolton DL, Pegu A, Wang K, McGinnis K, Nason M, Foulds K, Letukas V, Schmidt SD, Chen X, Todd JP, Lifson JD, Rao S, Michael NL, Robb ML, Mascola JR, Koup RA. Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs. J Virol. 2016 Feb 1;90(3):1321-32. doi: 10.1128/JVI.02454-15. Print 2016 Feb 1. PubMed PMID: 26581981; PubMed Central PMCID: PMC4719604.
  9. Bolton DL, Santra S, Swett-Tapia C, Custers J, Song K, Balachandran H, Mach L, Naim H, Kozlowski PA, Lifton M, Goudsmit J, Letvin N, Roederer M, Radošević K. Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates. Vaccine. 2012 Sep 7;30(41):5991-8. doi: 10.1016/j.vaccine.2012.06.029. Epub 2012 Jun 22. PubMed PMID: 22732429; PubMed Central PMCID: PMC3425710.
  10. Bolton DL, Song K, Wilson RL, Kozlowski PA, Tomaras GD, Keele BF, Lovingood RV, Rao S, Roederer M. Comparison of systemic and mucosal vaccination: impact on intravenous and rectal SIV challenge. Mucosal Immunol. 2012 Jan;5(1):41-52. doi: 10.1038/mi.2011.45. Epub 2011 Oct 26. PubMed PMID: 22031182; PubMed Central PMCID: PMC3732474.

Full bibliography link.