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.
- Member, Bioinformatics Graduate Program, Boston University
- Faculty, National Emerging Infectious Disease Lab, Boston University
- Member, Evans Center for Interdisciplinary Biomedical Research, Boston University
- Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Graduate Medical Sciences
- Member, Genome Science Institute, Boston University
- Brandeis University, PhD
- University of Massachusetts Boston, BA
- Published on 3/13/2020
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. PMID: 32231668.
- Published on 1/31/2020
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 Jan 31; 94(4). PMID: 31776278.
- Published on 1/23/2020
Feng F, Ataca ST, Ran M, Wang Y, Breen M, Kepler TB. Gain-Scanning for Protein Microarray Assays. J Proteome Res. 2020 Jan 23. PMID: 31928020.
- Published on 12/2/2019
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.
- Published on 10/2/2019
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. PMID: 31586542.
- Published on 9/17/2019
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.
- Published on 5/16/2019
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. PMID: 31100267.
- Published on 12/11/2018
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.
- Published on 7/25/2018
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.
- Published on 5/31/2018
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.
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