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




The B Cell Repertoire as a Window into the Nature and Impact of the Lung Virome
05/01/2017 - 04/30/2018 (PI)
NIH/National Heart, Lung, and Blood Institute
1R61HL137081-01

Modeling Affinity Maturation at Molecular Resolution
04/15/2015 - 03/31/2018 (PI)
NIH/National Institute of Allergy & Infectious Diseases
5U19AI117892-03

Neisserial Porins and Antigen Presenting Cells
09/01/2016 - 08/31/2017 (PI)
Boston Medical Center Corporation NIH NIAID
2R01AI040944-19A1

Research Training in Immunology
09/01/2014 - 08/31/2017 (PI)
NIH/National Institute of Allergy & Infectious Diseases
5T32AI007309-28

CHAVI-SRSC J Computational Biology
07/15/2012 - 06/30/2017 (PI)
Duke University NIH NIAID
5UM1AI100645-05

Structure-function Analysis of Infection and Vaccine-induced B-cell Repertoires (Core D)
01/01/2012 - 06/30/2017 (PI)
The Children's Hospital Corporation NIH NIAID
5P01AI089618-05

T and B Cell Mechanisms of HIV Control: Implications for Vaccine Design
09/01/2016 - 05/31/2017 (PI)
Massachusetts General Hospital Bill & Melinda Gates

HIV-1 vaccine-elicited antibodies target envelope glycans
06/01/2016 - 05/31/2017 (PI)
Duke University NIH NIAID
5R01AI20801-02

Statistical analysis of anti-tau and anti-influenza antibodies
09/01/2016 - 12/31/2016 (PI)
Janssen Vaccines & Prevention B.V.

B Cell Lineage Envelope Immunogen Design from RV144 Antibodies, Phase 2
11/01/2014 - 10/31/2016 (PI)
Duke University Bill & Melinda Gates

Showing 10 of 15 results. Show All Results



Yr Title Project-Sub Proj Pubs
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 Administrative Core 5U19AI117892-03-8835 2
2017 Model Development, Data Analysis, and Simulation for Affinity Maturation 5U19AI117892-03-8837 2
2016 Modeling affinity maturation at molecular resolution 5U19AI117892-02 2
2016 Research Training in Immunology 5T32AI007309-28 46
2016 Administrative Core 5U19AI117892-02-8835 2
2016 Model Development, Data Analysis, and Simulation for Affinity Maturation 5U19AI117892-02-8837 2
2016 Computational biology scientific research support component 4UM1AI100645-05-6367 100
2015 Modeling affinity maturation at molecular resolution 1U19AI117892-01 2
Showing 10 of 45 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. Kepler TB. Unconventional Interrogation Yields HIV''s Escape Plan. Cell Host Microbe. 2017 Jun 14; 21(6):659-660. PMID: 28618264.
  2. Bradley T, Pollara J, Santra S, Vandergrift N, Pittala S, Bailey-Kellogg C, Shen X, Parks R, Goodman D, Eaton A, Balachandran H, Mach LV, Saunders KO, Weiner JA, Scearce R, Sutherland LL, Phogat S, Tartaglia J, Reed SG, Hu SL, Theis JF, Pinter A, Montefiori DC, Kepler TB, Peachman KK, Rao M, Michael NL, Suscovich TJ, Alter G, Ackerman ME, Moody MA, Liao HX, Tomaras G, Ferrari G, Korber BT, Haynes BF. Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge. Nat Commun. 2017 Jun 08; 8:15711. PMID: 28593989.
  3. Cale EM, Gorman J, Radakovich NA, Crooks ET, Osawa K, Tong T, Li J, Nagarajan R, Ozorowski G, Ambrozak DR, Asokan M, Bailer RT, Bennici AK, Chen X, Doria-Rose NA, Druz A, Feng Y, Joyce MG, Louder MK, O''Dell S, Oliver C, Pancera M, Connors M, Hope TJ, Kepler TB, Wyatt RT, Ward AB, Georgiev IS, Kwong PD, Mascola JR, Binley JM. Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop. Immunity. 2017 May 16; 46(5):777-791.e10. PMID: 28514685.
  4. Bonsignori M, Kreider EF, Fera D, Meyerhoff RR, Bradley T, Wiehe K, Alam SM, Aussedat B, Walkowicz WE, Hwang KK, Saunders KO, Zhang R, Gladden MA, Monroe A, Kumar A, Xia SM, Cooper M, Louder MK, McKee K, Bailer RT, Pier BW, Jette CA, Kelsoe G, Williams WB, Morris L, Kappes J, Wagh K, Kamanga G, Cohen MS, Hraber PT, Montefiori DC, Trama A, Liao HX, Kepler TB, Moody MA, Gao F, Danishefsky SJ, Mascola JR, Shaw GM, Hahn BH, Harrison SC, Korber BT, Haynes BF. Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Sci Transl Med. 2017 Mar 15; 9(381). PMID: 28298420; DOI: 10.1126/scitranslmed.aai7514;.
  5. Alam SM, Aussedat B, Vohra Y, Ryan Meyerhoff R, Cale EM, Walkowicz WE, Radakovich NA, Anasti K, Armand L, Parks R, Sutherland L, Scearce R, Joyce MG, Pancera M, Druz A, Georgiev IS, Von Holle T, Eaton A, Fox C, Reed SG, Louder M, Bailer RT, Morris L, Abdool-Karim SS, Cohen M, Liao HX, Montefiori DC, Park PK, Fernández-Tejada A, Wiehe K, Santra S, Kepler TB, Saunders KO, Sodroski J, Kwong PD, Mascola JR, Bonsignori M, Moody MA, Danishefsky S, Haynes BF. Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide. Sci Transl Med. 2017 Mar 15; 9(381). PMID: 28298421; DOI: 10.1126/scitranslmed.aai7521;.
  6. Saunders KO, Nicely NI, Wiehe K, Bonsignori M, Meyerhoff RR, Parks R, Walkowicz WE, Aussedat B, Wu NR, Cai F, Vohra Y, Park PK, Eaton A, Go EP, Sutherland LL, Scearce RM, Barouch DH, Zhang R, Von Holle T, Overman RG, Anasti K, Sanders RW, Moody MA, Kepler TB, Korber B, Desaire H, Santra S, Letvin NL, Nabel GJ, Montefiori DC, Tomaras GD, Liao HX, Alam SM, Danishefsky SJ, Haynes BF. Vaccine Elicitation of High Mannose-Dependent Neutralizing Antibodies against the V3-Glycan Broadly Neutralizing Epitope in Nonhuman Primates. Cell Rep. 2017 Feb 28; 18(9):2175-2188. PMID: 28249163; DOI: 10.1016/j.celrep.2017.02.003;.
  7. Easterhoff D, Moody MA, Fera D, Cheng H, Ackerman M, Wiehe K, Saunders KO, Pollara J, Vandergrift N, Parks R, Kim J, Michael NL, O''Connell RJ, Excler JL, Robb ML, Vasan S, Rerks-Ngarm S, Kaewkungwal J, Pitisuttithum P, Nitayaphan S, Sinangil F, Tartaglia J, Phogat S, Kepler TB, Alam SM, Liao HX, Ferrari G, Seaman MS, Montefiori DC, Tomaras GD, Harrison SC, Haynes BF. Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial. PLoS Pathog. 2017 Feb; 13(2):e1006182. PMID: 28235027; DOI: 10.1371/journal.ppat.1006182;.
  8. Kepler TB, Wiehe K. Genetic and structural analyses of affinity maturation in the humoral response to HIV-1. Immunol Rev. 2017 Jan; 275(1):129-144. PMID: 28133793; DOI: 10.1111/imr.12513;.
  9. Bradley T, Yang G, Ilkayeva O, Holl TM, Zhang R, Zhang J, Santra S, Fox CB, Reed SG, Parks R, Bowman CM, Bouton-Verville H, Sutherland LL, Scearce RM, Vandergrift N, Kepler TB, Moody MA, Liao HX, Alam SM, McLendon R, Everitt JI, Newgard CB, Verkoczy L, Kelsoe G, Haynes BF. HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism. J Immunol. 2016 Dec 15; 197(12):4663-4673. PMID: 27849170.
  10. Raymond DD, Stewart SM, Lee J, Ferdman J, Bajic G, Do KT, Ernandes MJ, Suphaphiphat P, Settembre EC, Dormitzer PR, Del Giudice G, Finco O, Kang TH, Ippolito GC, Georgiou G, Kepler TB, Haynes BF, Moody MA, Liao HX, Schmidt AG, Harrison SC. Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain. Nat Med. 2016 Dec; 22(12):1465-1469. PMID: 27820604; DOI: 10.1038/nm.4223;.
Showing 10 of 155 results. Show More

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

Bar chart showing 155 publications over 29 distinct years, with a maximum of 11 publications in 2010

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
20149
201510
20167
20178
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

affinity maturation
antibody
B cell
bats
computational biology
mathematical modeling
systems biology
vaccine
wildlife immunology

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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