Thomas Kepler, PhD
Boston University School of Medicine
Dept of Microbiology

PhD, Brandeis University

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.

Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Graduate Medical Sciences

Boston University
Bioinformatics Graduate Program

Providence/Boston Center for AIDS Research (CFAR): Core Support (Cores A, B, E, G, K, SWG)
07/01/2018 - 06/30/2023 (PI of Sub-Project / SP)
PI: C. Robert Horsburgh Jr, MD
The Miriam Hospital NIH NIAID

Structure-function analysis of infection- and vaccine-induced B-cell repertoires
08/01/2017 - 07/31/2022 (PI)
The Children's Hospital Corporation NIH NIAID

Modeling Affinity Maturation at Molecular Resolution
04/15/2015 - 03/31/2020 (PI)
NIH/National Institute of Allergy & Infectious Diseases

Neisserial Porins and Antigen Presenting Cells
09/01/2016 - 08/31/2019 (PI)
Boston Medical Center Corporation NIH NIAID

Research Training in Immunology
09/01/2014 - 08/31/2019 (PI)
NIH/National Institute of Allergy & Infectious Diseases

CHAVI-SRSC J Computational Biology
07/15/2012 - 06/30/2019 (PI)
Duke University NIH NIAID

01/01/2012 - 06/30/2019 (PI)
Duke University NIH NIAID

HIV-1 vaccine-elicited antibodies target envelope glycans
06/01/2018 - 05/31/2019 (PI)
Duke University NIH NIAID

Statistical methods for HDX-MS and other protein-dynamic assays
05/01/2018 - 04/30/2019 (PI)
Vanderbilt University Medical Center NIH NIAID

The B cell repertoire as a window into the nature and impact of the lung virome
05/01/2017 - 04/30/2019 (PI)
NIH/National Heart, Lung, and Blood Institute

Showing 10 of 21 results. Show All Results

Yr Title Project-Sub Proj Pubs
2019 The B cell repertoire as a window into the nature and impact of the lung virome 4R33HL137081-03
2019 Modeling affinity maturation at molecular resolution 5U19AI117892-05 14
2019 Administrative Core 5U19AI117892-05-8835 14
2019 Model Development, Data Analysis, and Simulation for Affinity Maturation 5U19AI117892-05-8837 14
2018 The B cell repertoire as a window into the nature and impact of the lung virome 5R61HL137081-02 3
2018 Modeling affinity maturation at molecular resolution 5U19AI117892-04 14
2018 Research Training in Immunology 5T32AI007309-30 68
2018 Administrative Core 5U19AI117892-04-8835 14
2018 Model Development, Data Analysis, and Simulation for Affinity Maturation 5U19AI117892-04-8837 14
2018 Computational biology scientific research support component 5UM1AI100645-07-6367 261
Showing 10 of 60 results. Show All Results
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Watanabe A, McCarthy KR, Kuraoka M, Schmidt AG, Adachi Y, Onodera T, Tonouchi K, Caradonna TM, Bajic G, Song S, McGee CE, Sempowski GD, Feng F, Urick P, Kepler TB, Takahashi Y, Harrison SC, Kelsoe G. Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism. Cell. 2019 May 16; 177(5):1124-1135.e16.View Related Profiles. PMID: 31100267; DOI: 10.1016/j.cell.2019.03.048;.
  2. Bonsignori M, Scott E, Wiehe K, Easterhoff D, Alam SM, Hwang KK, Cooper M, Xia SM, Zhang R, Montefiori DC, Henderson R, Nie X, Kelsoe G, Moody MA, Chen X, Joyce MG, Kwong PD, Connors M, Mascola JR, McGuire AT, Stamatatos L, Medina-Ramírez M, Sanders RW, Saunders KO, Kepler TB, Haynes BF. Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier. Immunity. 2018 12 18; 49(6):1162-1174.e8. PMID: 30552024.
  3. Ferdman J, Palladino G, Liao HX, Moody MA, Kepler TB, Del Giudice G, Dormitzer PR, Harrison SC, Settembre EC, Suphaphiphat P. Intra-seasonal antibody repertoire analysis of a subject immunized with an MF59®-adjuvanted pandemic 2009 H1N1 vaccine. Vaccine. 2018 08 23; 36(35):5325-5332. PMID: 30055967.
  4. Wiehe K, Bradley T, Meyerhoff RR, Hart C, Williams WB, Easterhoff D, Faison WJ, Kepler TB, Saunders KO, Alam SM, Bonsignori M, Haynes BF. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe. 2018 06 13; 23(6):759-765.e6. PMID: 29861171.
  5. Pavlovich SS, Lovett SP, Koroleva G, Guito JC, Arnold CE, Nagle ER, Kulcsar K, Lee A, Thibaud-Nissen F, Hume AJ, Mühlberger E, Uebelhoer LS, Towner JS, Rabadan R, Sanchez-Lockhart M, Kepler TB, Palacios G. The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity. Cell. 2018 05 17; 173(5):1098-1110.e18.View Related Profiles. PMID: 29706541.
  6. McCarthy KR, Watanabe A, Kuraoka M, Do KT, McGee CE, Sempowski GD, Kepler TB, Schmidt AG, Kelsoe G, Harrison SC. Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires. Immunity. 2018 01 16; 48(1):174-184.e9. PMID: 29343437.
  7. Williams WB, Zhang J, Jiang C, Nicely NI, Fera D, Luo K, Moody MA, Liao HX, Alam SM, Kepler TB, Ramesh A, Wiehe K, Holland JA, Bradley T, Vandergrift N, Saunders KO, Parks R, Foulger A, Xia SM, Bonsignori M, Montefiori DC, Louder M, Eaton A, Santra S, Scearce R, Sutherland L, Newman A, Bouton-Verville H, Bowman C, Bomze H, Gao F, Marshall DJ, Whitesides JF, Nie X, Kelsoe G, Reed SG, Fox CB, Clary K, Koutsoukos M, Franco D, Mascola JR, Harrison SC, Haynes BF, Verkoczy L. Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations. Nat Commun. 2017 11 23; 8(1):1732.View Related Profiles. PMID: 29170366.
  8. Breden F, Luning Prak ET, Peters B, Rubelt F, Schramm CA, Busse CE, Vander Heiden JA, Christley S, Bukhari SAC, Thorogood A, Matsen Iv FA, Wine Y, Laserson U, Klatzmann D, Douek DC, Lefranc MP, Collins AM, Bubela T, Kleinstein SH, Watson CT, Cowell LG, Scott JK, Kepler TB. Reproducibility and Reuse of Adaptive Immune Receptor Repertoire Data. Front Immunol. 2017; 8:1418. PMID: 29163494.
  9. Ramesh A, Darko S, Hua A, Overman G, Ransier A, Francica JR, Trama A, Tomaras GD, Haynes BF, Douek DC, Kepler TB. Structure and Diversity of the Rhesus Macaque Immunoglobulin Loci through Multiple De Novo Genome Assemblies. Front Immunol. 2017; 8:1407.View Related Profiles. PMID: 29163486.
  10. Han Q, Williams WB, Saunders KO, Seaton KE, Wiehe KJ, Vandergrift N, Von Holle TA, Trama AM, Parks RJ, Luo K, Gurley TC, Kepler TB, Marshall DJ, Montefiori DC, Sutherland LL, Alam MS, Whitesides JF, Bowman CM, Permar SR, Graham BS, Mascola JR, Seed PC, Van Rompay KKA, Tomaras GD, Moody MA, Haynes BF. HIV DNA-Adenovirus Multiclade Envelope Vaccine Induces gp41 Antibody Immunodominance in Rhesus Macaques. J Virol. 2017 Nov 01; 91(21). PMID: 28794027.
Showing 10 of 170 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 170 publications over 31 distinct years, with a maximum of 14 publications in 2017


Available to Mentor as: (Review Mentor Role Definitions):
  • Advisor
  • Research / Scholarly Mentor
Contact for Mentoring:

72 E. Concord St Instructional (L)
Boston MA 02118
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