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.

Faculty
Boston University
National Emerging Infectious Disease Lab


Member
Boston University
Evans Center for Interdisciplinary Biomedical Research


Member
Boston University
Genome Science Institute


Member
Boston University
Bioinformatics Graduate Program


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




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)
The Miriam Hospital NIH NIAID
5P30AI042853-21

Structure-function analysis of infection- and vaccine-induced B-cell repertoires
08/01/2017 - 07/31/2022 (Subcontract PI)
The Children's Hospital Corporation NIH NIAID
5P01AI089618-08

The B cell repertoire as a window into the nature and impact of the lung virome
05/01/2019 - 04/30/2022 (Multi-PI)
PI: Thomas Kepler, PhD
NIH/National Heart, Lung, and Blood Institute
4R33HL137081-03

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

Structure based design of antibodies and vaccines
05/01/2019 - 04/30/2020 (Subcontract PI)
Vanderbilt University Medical Center NIH NIAID
5U19AI117905-05

Modeling Affinity Maturation at Molecular Resolution
04/15/2015 - 03/31/2020 (PI)
NIH/National Institute of Allergy & Infectious Diseases
5U19AI117892-05

Neisserial Porins and Antigen Presenting Cells
09/01/2016 - 08/31/2019 (Subcontract PI)
Boston Medical Center Corporation NIH NIAID
5R01AI040944-21

Research Training in Immunology
09/01/2014 - 08/31/2019 (PI)
NIH/National Institute of Allergy & Infectious Diseases
5T32AI007309-30

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

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

Showing 10 of 23 results. Show All Results


Title


Yr Title Project-Sub Proj Pubs
2020 The B cell repertoire as a window into the nature and impact of the lung virome 5R33HL137081-04
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 Administrative Core 5U19AI117892-05-8835 17
2019 Model Development, Data Analysis, and Simulation for Affinity Maturation 5U19AI117892-05-8837 17
2019 Computational Core 5P01AI089618-08-5809 24
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 17
2018 Research Training in Immunology 5T32AI007309-30 73
2018 Administrative Core 5U19AI117892-04-8835 17
Showing 10 of 62 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. 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
     
  2. 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
     
  3. Feng F, Ataca ST, Ran M, Wang Y, Breen M, Kepler TB. Gain-Scanning for Protein Microarray Assays. J Proteome Res. 2020 Jul 02; 19(7):2664-2675.View Related Profiles. PMID: 31928020
     
  4. 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
     
  5. Gorman J, Mason RD, Nettey L, Cavett N, Chuang GY, Peng D, Tsybovsky Y, Verardi R, Nguyen R, Ambrozak D, Biris K, LaBranche CC, Ramesh A, Schramm CA, Zhou J, Bailer RT, Kepler TB, Montefiori DC, Shapiro L, Douek DC, Mascola JR, Roederer M, Kwong PD. Isolation and Structure of an Antibody that Fully Neutralizes Isolate SIVmac239 Reveals Functional Similarity of SIV and HIV Glycan Shields. Immunity. 2019 10 15; 51(4):724-734.e4.View Related Profiles. PMID: 31586542
     
  6. 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. 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 09; 15(9):e1008026. PMID: 31527908
     
  7. 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 05 16; 177(5):1124-1135.e16.View Related Profiles. PMID: 31100267; DOI: 10.1016/j.cell.2019.03.048;
     
  8. 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
     
  9. 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
     
  10. 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
     
Showing 10 of 176 results. Show More

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

Bar chart showing 176 publications over 32 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
20203

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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