Thomas Kepler, PhD
Emeritus Professor
Boston University Chobanian & Avedisian School of Medicine
Virology, Immunology & Microbiology

PhD, Brandeis University
BA, University of Massachusetts Boston



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.

Faculty
Boston University
National Emerging Infectious Disease Lab




Research Training in Immunology
08/24/2020 - 07/31/2025 (PI of Sub-Project / SP)
PI: Suryaram Gummuluru, PhD
NIH/National Institute of Allergy & Infectious Diseases
5T32AI007309-34

Structure-function analysis of infection- and vaccine-induced B-cell repertoires
08/01/2017 - 07/31/2023 (Subcontract PI)
The Children's Hospital Corporation NIH NIAID
5P01AI089618-10

Providence/Boston Center for AIDS Research (CFAR): Core Support (Cores A, B, E, G, K, SWG)
07/01/2018 - 06/30/2023 (Co-Investigator of Sub-Project / SP)
The Miriam Hospital NIH NIAID
5P30AI042853-24

HIV-1 vaccine-elicited antibodies target envelope glycans
06/01/2016 - 05/31/2023 (Subcontract PI)
Duke University NIH NIAID
5R01AI20801-03

The B cell repertoire as a window into the nature and impact of the lung virome
05/01/2019 - 04/30/2023 (Multi-PI)
PI: Thomas Kepler, PhD
NIH/National Heart, Lung, and Blood Institute
5R33HL137081-05

Immune Mechanisms of Protection against Mycobacterium Tuberculosis Center (IMPAc-TB)
09/30/2019 - 06/30/2022 (Subcontract PI)
President and Fellows of Harvard College dba Harvard T.H. Chan School of Public Health NIH NIAID


Modeling Affinity Maturation at Molecular Resolution
04/15/2015 - 03/31/2022 (PI)
NIH/National Institute of Allergy & Infectious Diseases
5U19AI117892-05

Neisserial Porins and Antigen Presenting Cells
09/01/2016 - 08/31/2021 (Subcontract PI)
Boston Medical Center Corporation NIH NIAID
5R01AI040944-22

Structure Based Design of Antibodies and Vaccines
05/01/2019 - 04/30/2021 (Subcontract PI)
Vanderbilt University Medical Center NIH NIAID
5U19AI117905-05

HIV-1 vaccine-elicited antibodies target envelope glycans
06/01/2018 - 05/31/2020 (Subcontract PI)
Duke University NIH NIAID
5R01AI120801-05

Showing 10 of 25 results. Show All Results


Title


Yr Title Project-Sub Proj Pubs
2022 Research Training in Immunology 5T32AI007309-33
2021 The B cell repertoire as a window into the nature and impact of the lung virome 5R33HL137081-05
2021 Computational Core 5P01AI089618-10-5809 24
2021 Research Training in Immunology 5T32AI007309-32 73
2020 The B cell repertoire as a window into the nature and impact of the lung virome 5R33HL137081-04
2020 Computational Core 5P01AI089618-09-5809 24
2020 Research Training in Immunology 2T32AI007309-31A1 73
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 17
2019 Computational Core 5P01AI089618-08-5809 24
Showing 10 of 68 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.

iCite Analysis       Copy PMIDs To Clipboard

  1. 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.View Related Profiles. PMID: 38269092; PMCID: PMC10805652; DOI: 10.1016/j.isci.2023.108749;
     
  2. 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.View Related Profiles. PMID: 37314411; PMCID: PMC10352589; DOI: 10.4049/jimmunol.2200340;
     
  3. Kepler T, Flanagan S, Hoegerl C. Urgency in the Treatment of Sudden Sensorineural Hearing Loss. Cureus. 2023 Jun; 15(6):e40409. PMID: 37456426; PMCID: PMC10348034; DOI: 10.7759/cureus.40409;
     
  4. 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; PMCID: PMC9883670; DOI: 10.1016/j.celrep.2022.111628;
     
  5. 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; PMCID: PMC9130890; DOI: 10.1002/advs.202200063;
     
  6. Roark RS, Li H, Williams WB, Chug H, Mason RD, Gorman J, Wang S, Lee FH, Rando J, Bonsignori M, Hwang KK, Saunders KO, Wiehe K, Moody MA, Hraber PT, Wagh K, Giorgi EE, Russell RM, Bibollet-Ruche F, Liu W, Connell J, Smith AG, DeVoto J, Murphy AI, Smith J, Ding W, Zhao C, Chohan N, Okumura M, Rosario C, Ding Y, Lindemuth E, Bauer AM, Bar KJ, Ambrozak D, Chao CW, Chuang GY, Geng H, Lin BC, Louder MK, Nguyen R, Zhang B, Lewis MG, Raymond DD, Doria-Rose NA, Schramm CA, Douek DC, Roederer M, Kepler TB, Kelsoe G, Mascola JR, Kwong PD, Korber BT, Harrison SC, Haynes BF, Hahn BH, Shaw GM. Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth. Science. 2021 01 08; 371(6525). PMID: 33214287; PMCID: PMC8040783; DOI: 10.1126/science.abd2638;
     
  7. Pavlovich SS, Darling T, Hume AJ, Davey RA, Feng F, Mühlberger E, Kepler TB. Egyptian Rousette IFN-? Subtypes Elicit Distinct Antiviral Effects and Transcriptional Responses in Conspecific Cells. Front Immunol. 2020; 11:435.View Related Profiles. PMID: 32231668; PMCID: PMC7083018; DOI: 10.3389/fimmu.2020.00435;
     
  8. Easterhoff D, Pollara J, Luo K, Tolbert WD, Young B, Mielke D, Jha S, O'Connell RJ, Vasan S, Kim J, Michael NL, Excler JL, Robb ML, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Nitayaphan S, Sinangil F, Tartaglia J, Phogat S, Kepler TB, Alam SM, Wiehe K, Saunders KO, Montefiori DC, Tomaras GD, Moody MA, Pazgier M, Haynes BF, Ferrari G. Boosting with AIDSVAX B/E Enhances Env Constant Region 1 and 2 Antibody-Dependent Cellular Cytotoxicity Breadth and Potency. J Virol. 2020 01 31; 94(4). PMID: 31776278; PMCID: PMC6997759; DOI: 10.1128/JVI.01120-19;
     
  9. Feng F, Ataca ST, Ran M, Wang Y, Breen M, Kepler TB. Gain-Scanning for Protein Microarray Assays. J Proteome Res. 2020 07 02; 19(7):2664-2675.View Related Profiles. PMID: 31928020; PMCID: PMC7783788; DOI: 10.1021/acs.jproteome.9b00892;
     
  10. LaBranche CC, Henderson R, Hsu A, Behrens S, Chen X, Zhou T, Wiehe K, Saunders KO, Alam SM, Bonsignori M, Borgnia MJ, Sattentau QJ, Eaton A, Greene K, Gao H, Liao HX, Williams WB, Peacock J, Tang H, Perez LG, Edwards RJ, Kepler TB, Korber BT, Kwong PD, Mascola JR, Acharya P, Haynes BF, Montefiori DC. Correction: Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies. PLoS Pathog. 2019 Dec; 15(12):e1008200. PMID: 31790514; PMCID: PMC6886749; DOI: 10.1371/journal.ppat.1008200;
     
Showing 10 of 182 results. Show More

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

Bar chart showing 182 publications over 34 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
20185
20194
20204
20222
20233

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

650 Albany St
Boston MA 02118
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