Krista Freeman
Case Western Reserve University, OH·Biomedical Engineering·Early-career
Bacteriophages, or phages, are viruses that infect bacteria. They are drawing renewed interest as treatments for bacterial infections and as vaccine platforms.
- Fields
Biomedical Engineering
Microbiology & Immunology
- Topics
bacteriophages
phage therapy
phage immunogenicity
- Grants
- 1 known grant, through Jul 2027
What they work on
- Map where antibodies bind three therapeutic mycobacteriophages using structural biology, including asymmetric reconstructions of phage-antibody complexes.
- Generate mutant phages that escape antibody binding through structure-guided engineering and directed evolution, and test in a mouse model whether they evade immunity raised against the original phages.
- Develop these phages into a therapeutic bacterial vaccine using phage display and phage DNA vectors that kills bacteria, raises bacteria-binding antibodies, and activates helper and cytotoxic T cells.
- Test whether co-administering phages with rapamycin-loaded nanoparticles reduces phage-specific helper T cells and increases regulatory T cells, training the immune system to tolerate phage.
More about the research
As antimicrobials, phages are well tolerated, attack only their target bacteria and multiply at the infection site. As vaccines, they can be engineered to carry many foreign antigens, the molecules the immune system learns to recognize. But the immune system also reacts to the phage itself. Antibodies can neutralize a therapeutic phage before it kills its target, and strong responses to phage proteins can distract from the protective response a vaccine is meant to produce. Little is known about phage immunology, and this project studies why phages trigger immune responses and how to adjust those responses.
Why it matters
Antibiotic-resistant and emerging bacterial pathogens need new defenses. Phage therapies and phage vaccines are promising, but immune reactions to phages can limit them. Engineering phages that dodge antibodies, tuning vaccine responses, and training tolerance with rapamycin nanoparticles could make phage-based treatments more effective for patients with hard-to-treat bacterial infections.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Kai Xu
Ohio State University, OH·Biophysics
Determine structures of soluble, stabilized G and F glycoprotein ectodomains from emerging henipaviruses, including the bat-borne Cedar virus and Angavokely virus, to capture the full tetrameric G and the fragile prefusion F.
Yoshihiro Kawaoka
University of Wisconsin-Madison, WI·Microbiology & Immunology
Engineer influenza B hemagglutinin mutants whose antigenic properties lie between the virus's two major lineages, using mutagenesis, to create antigens that may elicit antibodies protecting against both lineages.
David Veesler
University of Washington, WA·Microbiology & Immunology
Characterize how broadly serum antibodies from nonhuman primates immunized with nanoparticle vaccines co-displaying multiple receptor-binding-domain and spike antigens bind and neutralize betacoronaviruses.
The school
Case Western Reserve University: 34 labs on PI Pages, $643M a year on research, 213 research doctorates a year.
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