Thomas B. Kepler, PhD

Emeritus Professor, Boston University Chobanian & Avedisian School of Medicine

Biography

The Kepler laboratory develops computational tools and applies them in the context of systems-level experimentation to address outstanding questions in immunology and vaccine development. Much of their work is centered on antibodies and the cells (B cells) that produce them.

Antibodies are genetically extraordinary: their genes are encoded only as fragments in the genome. The B cell’s genome must be cut, rearranged and re-ligated in several places to make the genes required for antibody production. Furthermore, after a B cell has encountered a molecule that binds its antibody (whether on a pathogen, an infected cell, a cancerous tumor, or, in the case of autoimmune disease, normal tissue) the B cell directs mutations into its rearranged antibody genes, and is then subject to competitive selection for improved ability to bind the eliciting molecule. In this Darwinian process, known as affinity maturation, the antibody response is rapidly improved and prepared as the memory response that confers long-term immunity and serves as the basis for vaccination.

The Kepler group works with multiple collaborating laboratories to generate and integrate data from many different assays, each of which provides one perspective on the workings of affinity maturation. By using computational means to coordinate the integration of these diverse data, a comprehensive picture of the process at a systems level emerges.

Professor Kepler, in partnership with colleagues at Duke and Harvard Universities, has developed a new approach to vaccination that uses computational methods to select combinations of immunogens to use in vaccines that drive affinity maturation in specific directions. These methods are being used to develop vaccines against HIV, influenza, and anthrax.

Publications

  • Published 12/14/2023

    Feng F, Yuen R, Wang Y, Hua A, Kepler TB, Wetzler LM. Characterizing adjuvants' effects at murine immunoglobulin repertoire level. iScience. 2024 Jan 19; 27(1):108749. PMID: 38269092.

    Read at: PubMed

  • Published 8/1/2023

    Aihara F, Wang Y, Belkina AC, Fearns R, Mizgerd JP, Feng F, Kepler TB. Diversity of B Cell Populations and Ig Repertoire in Human Lungs. J Immunol. 2023 Aug 01; 211(3):486-496. PMID: 37314411.

    Read at: PubMed

  • Published 6/14/2023

    Kepler T, Flanagan S, Hoegerl C. Urgency in the Treatment of Sudden Sensorineural Hearing Loss. Cureus. 2023 Jun; 15(6):e40409. PMID: 37456426.

    Read at: PubMed

  • Published 11/8/2022

    Caradonna TM, Ronsard L, Yousif AS, Windsor IW, Hecht R, Bracamonte-Moreno T, Roffler AA, Maron MJ, Maurer DP, Feldman J, Marchiori E, Barnes RM, Rohrer D, Lonberg N, Oguin TH, Sempowski GD, Kepler TB, Kuraoka M, Lingwood D, Schmidt AG. An epitope-enriched immunogen expands responses to a conserved viral site. Cell Rep. 2022 Nov 08; 41(6):111628. PMID: 36351401.

    Read at: PubMed

  • Published 3/23/2022

    Gao N, Gai Y, Meng L, Wang C, Wang W, Li X, Gu T, Louder MK, Doria-Rose NA, Wiehe K, Nazzari AF, Olia AS, Gorman J, Rawi R, Wu W, Smith C, Khant H, de Val N, Yu B, Luo J, Niu H, Tsybovsky Y, Liao H, Kepler TB, Kwong PD, Mascola JR, Qin C, Zhou T, Yu X, Gao F. Development of Neutralization Breadth against Diverse HIV-1 by Increasing Ab-Ag Interface on V2. Adv Sci (Weinh). 2022 May; 9(15):e2200063. PMID: 35319830.

    Read at: PubMed

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Other Positions

  • Faculty, National Emerging Infectious Disease Lab
    Boston University

Websites

Education

  • Brandeis University, PhD
  • University of Massachusetts Boston, BA

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