Faculty

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Daniel Claiborne, PhD

Wistar Institute Assistant Professor of Microbiology

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Department: Microbiology

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1f Graduate Group Affiliations 8

Cell and Molecular Biology

46 Contact information
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3601 Spruce Street
Philadelphia, PA 19104

30 Office: (215) 898-2203
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Email:
dclaiborne@wistar.org

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18 Publications
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26 Search PubMed for articles c

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13 Education:
21 7 BS 19 (Biochemistry) c
31 Florida State University, 2008.
21 8 PhD 32 (Immunology and Molecular Pathogenesis) c
29 Emory University, 2014.
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Links
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5 3 3 92 Permanent link
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b6 > Perelman School of Medicine > Faculty > Details a

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Description of Research Expertise

23 Research Interests
c6 The Claiborne lab is interested in understanding the mechanistic determinants of T cell dysfunction in chronic infections such as HIV in order to engineer more potent T cell immunotherapies.
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11 Keywords
54 HIV, HIV pathogenesis, CAR T cell therapy, T cell exhaustion, humanized mice
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18 Research Details
236 T cell immunotherapies offer hope for the treatment of malignancies and other chronic diseases. However, natural mechanisms in place to limit immune-mediated pathology ultimately attenuate the T cell response in the setting of chronic antigen exposure, such as is found in chronic viral diseases – including HIV – as well as cancer. A better understanding of the mechanisms underlying T cell exhaustion has the potential to revolutionize T cell immunotherapies, such as chimeric antigen receptor (CAR) T cell therapy, for the treatment of human disease.
313 The Claiborne lab is rooted in understanding the complex interplay between the virus and the host in HIV transmission, pathogenesis, and persistence. A central focus of the lab is the optimization of CAR T cell therapy for a functional HIV cure. Concordant with efforts to engineer potent CAR T cell therapies against HIV, the Claiborne lab seeks to uncover the mechanisms behind the initiation and maintenance of dysfunctional T cell phenotypes, as the pursuit of these questions is critical to developing the next generation of T cell immunotherapies. To answer these complex questions, the lab leverages the powerful in vivo model system of HIV-infected humanized mice coupled with HIV-directed CAR T cells to study the evolution of antigen-specific T cell function over time.
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1a Rotation Projects
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4e Influence of viral characteristics on HIV-specific CAR T cell function
311 Previous work by the lab has demonstrated that the intrinsic viral replicative capacity (vRC) of the transmitted/founder virus can greatly impact the disease course of HIV-infected individuals. Individuals infected with high-vRC variants display exacerbated immunopathology characterized by T cell activation and exhaustion, concomitant with rapid CD4+ T cell loss. This may also represent an unrecognized hurdle for a functional HIV cure, as individuals with high-vRC viruses may be more refractory to CAR T cell therapy or other interventions. The lab endeavors to use a previously generated suite of chimeric viruses exhibiting distinct vRC phenotypes to define the extent to which vRC affects CAR T efficacy in vitro and in vivo and to elucidate the mechanisms responsible.
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16 Lab Personnel
2a Madison Werts (Research Assistant)
27 Tyler Yang (Research Assistant)
2c Reyes Acosta (Graduate Student, CAMB)
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Selected Publications

178 Maldini CR, Claiborne DT, Okawa K, Chen T, Dopkin DL, Shan X, Power KA, Trifonova RT, Krupp K, Phelps M, Vrbanac VD, Tanno S, Bateson T, Leslie GJ, Hoxie JA, Boutwell CL, Riley JL, Allen TM.: Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo. Nat Med 2020.

16e Claiborne DT, Dudek TE, Maldini CR, Power KA, Ghebremichael M, Seung E, Mellors EF, Vrbanac VD, Krupp K, Bisesi A, Tager AM, Knipe DM, Boutwell CL, Allen TM.: Immunization of BLT Humanized Mice Redirects T Cell Responses to Gag and Reduces Acute HIV-1 Viremia. J Virol 93: e00814-19, Sep 2019.

1a1 Garcia-Beltran WF, Claiborne DT, Maldini CR, Phelps M, Vrbanac V, Karpel ME, Krupp KL, Power KA, Boutwell CL, Balazs AB, Tager AM, Altfeld M, Allen TM.: Innate Immune Reconstitution in Humanized Bone Marrow-Liver-Thymus (HuBLT) Mice Governs Adaptive Cellular Immune Function and Responses to HIV-1 Infection. Front Immunol 12: 667393, May 2021.

1f3 Calvet-Mirabent M, Claiborne DT, Deruaz M, Tanno S, Serra C, Delgado-Arévalo C, Sánchez-Cerrillo I, de Los Santos I, Sanz J, García-Fraile L, Sánchez-Madrid F, Alfranca A, Muñoz-Fernández MÁ, Allen TM, Buzón MJ, Balazs A, Vrbanac V, Martín-Gayo E.: Poly I:C and STING agonist-primed DC increase lymphoid tissue polyfunctional HIV-1-specific CD8(+) T cells and limit CD4(+) T-cell loss in BLT mice. Eur J Immunol 2022.

218 Claiborne DT, Prince JL, Scully E, Macharia G, Micci L, Lawson B, Kopycinski J, Deymier MJ, Vanderford TH, Nganou-Makamdop K, Ende Z, Brooks K, Tang J, Yu T, Lakhi S, Kilembe W, Silvestri G, Douek D, Goepfert PA, Price MA, Allen SA, Paiardini M, Altfeld M, Gilmour J, Hunter E.: Replicative fitness of transmitted HIV-1 drives acute immune activation, proviral load in memory CD4+ T cells, and disease progression. Proc Natl Acad Sci U S A 112: E1480-9, Mar 2015.

1aa Prince JL, Claiborne DT, Carlson JM, Schaefer M, Yu T, Lahki S, Prentice HA, Yue L, Vishwanathan SA, Kilembe W, Goepfert P, Price MA, Gilmour J, Mulenga J, Farmer P, Derdeyn CA, Tang J, Heckerman D, Kaslow RA, Allen SA, Hunter E.: Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis. PLoS Pathog 2012.

1ca Claiborne DT, Scully EP, Palmer CD, Prince JL, Macharia GN, Kopycinski J, Michelo CM, Wiener HW, Parker R, Nganou-Makamdop K, Douek D, Altfeld M, Gilmour J, Price MA, Tang J, Kilembe W, Allen SA, Hunter E.: Protective HLA alleles are associated with reduced LPS levels in acute HIV infection with implications for immune activation and pathogenesis. PLoS Pathog 15: e1007981, Aug 2019.

1ae Mónaco DC, Dilernia DA, Fiore-Gartland A, Yu T, Prince JL, Dennis KK, Qin K, Schaefer M, Claiborne DT, Kilembe W, Tang J, Price MA, Farmer P, Gilmour J, Bansal A, Allen S, Goepfert P, Hunter E.: Balance between transmitted HLA preadapted and nonassociated polymorphisms is a major determinant of HIV-1 disease progression. J Exp Med 213: 2049-63, Sep 2016.

1d2 Carlson JM, Schaefer M, Monaco DC, Batorsky R, Claiborne DT, Prince J, Deymier MJ, Ende ZS, Klatt NR, DeZiel CE, Lin TH, Peng J, Seese AM, Shapiro R, Frater J, Ndung'u T, Tang J, Goepfert P, Gilmour J, Price MA, Kilembe W, Heckerman D, Goulder PJ, Allen TM, Allen S, Hunter E.: HIV transmission. Selection bias at the heterosexual HIV-1 transmission bottleneck. Science 345: 1254031, Jul 2014.

112 Ende Z, Deymier MJ, Claiborne DT, Prince JL, Mónaco DC, Kilembe W, Allen SA, Hunter E.: HLA Class I Downregulation by HIV-1 Variants from Subtype C Transmission Pairs. J Virol 92: e01633-17, Mar 2018.

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