Thomas Kepler, PhD
Professor
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, Division of Graduate Medical Sciences


Member
Boston University
Bioinformatics Graduate Program




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
2P01AI089618-06

Modeling Affinity Maturation at Molecular Resolution
04/15/2015 - 03/31/2020 (PI)
NIH/National Institute of Allergy & Infectious Diseases
5U19AI117892-04

Research Training in Immunology
09/01/2014 - 08/31/2019 (PI)
NIH/National Institute of Allergy & Infectious Diseases
5T32AI007309-29

CHAVI-SRSC J Computational Biology
07/15/2012 - 06/30/2019 (PI)
Duke University NIH NIAID
5UM1AI100645-06

CHAVI
01/01/2012 - 06/30/2019 (PI)
Duke University NIH NIAID
1UM1AI100645-01

Statistical methods for HDX-MS and other protein-dynamic assays
05/01/2018 - 04/30/2019 (PI)
Vanderbilt University Medical Center NIH NIAID
5U19AI117905-04

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
5R61HL137081-02

Immune signatures of differential NHP granuloma states
07/01/2017 - 12/31/2018 (PI)
Harvard School of Public Health Bill & Melinda Gates

Neisserial Porins and Antigen Presenting Cells
09/01/2016 - 08/31/2018 (PI)
Boston Medical Center Corporation NIH NIAID
5R01AI040944-20

Lifespan/Tufts/brown Center for AIDS Research (CFAR): Core A, Core B, Core G and SWG1
07/01/2016 - 06/30/2018 (PI of Sub-Project / SP)
PI: C. Robert Horsburgh Jr, MD
The Miriam Hospital NIH NIAID
3P30AI042853-19S1

Showing 10 of 19 results. Show All Results



Yr Title Project-Sub Proj Pubs
2018 The B cell repertoire as a window into the nature and impact of the lung virome 5R61HL137081-02
2018 Modeling affinity maturation at molecular resolution 5U19AI117892-04 2
2018 Administrative Core 5U19AI117892-04-8835 2
2018 Model Development, Data Analysis, and Simulation for Affinity Maturation 5U19AI117892-04-8837 2
2018 Computational biology scientific research support component 5UM1AI100645-07-6367 100
2017 The B cell repertoire as a window into the nature and impact of the lung virome 1R61HL137081-01
2017 Modeling affinity maturation at molecular resolution 5U19AI117892-03 2
2017 Computational Core 2P01AI089618-06-5809 4
2017 Research Training in Immunology 5T32AI007309-29 46
2017 Administrative Core 5U19AI117892-03-8835 2
Showing 10 of 52 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. 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.
     
  2. 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 Jun 13; 23(6):759-765.e6. PMID: 29861171.
     
  3. 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 May 17; 173(5):1098-1110.e18.View Related Profiles. PMID: 29706541.
     
  4. 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.
     
  5. 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 Nov 23; 8(1):1732.View Related Profiles. PMID: 29170366.
     
  6. 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.
     
  7. 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.
     
  8. 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.
     
  9. Hwang JK, Wang C, Du Z, Meyers RM, Kepler TB, Neuberg D, Kwong PD, Mascola JR, Joyce MG, Bonsignori M, Haynes BF, Yeap LS, Alt FW. Sequence intrinsic somatic mutation mechanisms contribute to affinity maturation of VRC01-class HIV-1 broadly neutralizing antibodies. Proc Natl Acad Sci U S A. 2017 08 08; 114(32):8614-8619. PMID: 28747530.
     
  10. Kepler TB. Unconventional Interrogation Yields HIV's Escape Plan. Cell Host Microbe. 2017 Jun 14; 21(6):659-660. PMID: 28618264.
     
Showing 10 of 168 results. Show More

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

Bar chart showing 167 publications over 30 distinct years, with a maximum of 14 publications in 2017

YearPublications
19881
19892
19906
19915
19923
19934
19954
19961
19972
19985
19995
20003
20018
20025
20033
20044
20056
20064
20074
20089
20095
201011
20118
20124
20139
201412
201510
20167
201714
20183

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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