Masahiro Yamashita
Columbia University, NY·Microbiology & Immunology
HIV is a moving target. Within a single infected person the virus exists as a swarm of slightly different variants, and those variants differ in how well antibodies can block them.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Genetics
- Topics
broadly neutralizing antibodies
bNAbs
envelope glycoprotein
- Grants
- 2 known grants, through May 2028
What they work on
- Develop a high-throughput neutralization assay in which each HIV envelope (Env) variant in a lentiviral system carries a unique DNA barcode, allowing simultaneous tracking of hundreds of variants against ten broadly neutralizing antibodies targeting five gp120 sites.
- Replace single-genome amplification with Nanopore long-read sequencing of bulk Env templates and train machine learning models on neutralization data to predict antibody susceptibility from sequence.
- Test whether a virion capture assay can enrich functional Env proteins and whether DNA analysis can recover minority variants from the latent HIV reservoir, using specimens from ACTG and HVTN biorepositories.
- Build comprehensive resistance profiles for HIV-1 capsid inhibitors by high-throughput mutational analysis, and test whether combining inhibitor classes increases antiviral activity or restricts escape pathways.
- Determine how HIV-1 exploits host factors through the charged central pore of each capsid protein ring, comparing host factor requirements across lentiviruses and applying deep mutational scanning to the pore.
- Test whether the capsid shields viral DNA from innate DNA sensors during cell-to-cell transmission, using HIV-1 variants with different uncoating speeds plus new assays for viral latency and competition in co-culture.
More about the research
Two projects address this variability from different angles: one builds laboratory and computational tests to tell quickly whether a patient's virus can be neutralized by antibody therapies, the other asks how far the virus's protein shell can mutate and what that means for a new class of drugs.
Why it matters
Knowing in advance whether someone's virus can be neutralized would change how antibody trials enroll participants and how resistance is detected, improving the evaluation and eventual clinical use of broadly neutralizing antibodies for HIV treatment and prevention. The capsid work maps how readily the virus escapes capsid-targeting drugs, knowledge that could guide design of more durable antivirals and smarter drug combinations.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Hillel Haim
University of Iowa, IA·Microbiology & Immunology
Build a deep mutational scanning system using replication-defective HIV-1 to measure, safely and at high throughput, how every amino acid substitution at each site of the capsid protein affects viral fitness and resistance to the capsid inhibitor lenacapavir.
Jeannette Tenthorey
University of California-San Francisco, CA·Microbiology & Immunology·Early-career
Build stable, high-complexity HIV-1 libraries containing all possible single missense mutations across the capsid, using new tools that overcome long-standing barriers to producing saturating mutant viral libraries.
Ashley Nelson
Weill Medical College of Cornell University, NY·Microbiology & Immunology
Compare giving germline-targeting HIV envelope immunogens one after another versus all at once for waking up precursor B cells of two broadly neutralizing antibody classes: those binding the CD4 binding site and those binding the V2 apex of the viral spike.
The school
Columbia University: 89 labs on PI Pages, $1.4B a year on research, 625 research doctorates a year.
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