Taisuke Izumi
American University, DC·Microbiology & Immunology
Modern antiviral drug combinations can push HIV down to undetectable levels in the blood, yet more than half of people living with the virus still develop problems with memory, attention and thinking, grouped under the term HIV-associated neurocognitive disorders (HAND). Part of the reason is that the virus hides in long-lived cells inside the brain and spinal cord, especially microglia — the brain's resident immune cells.
- Fields
Microbiology & Immunology
Neuroscience
Pharmacology
- Topics
HIV latency
latent reservoir
HIV-associated neurocognitive disorders
- Grants
- 1 known grant, through Jul 2029
What they work on
- Test in cell culture whether combining PARP inhibitors with HDAC inhibitors reverses HIV latency more effectively in microglia, using human C20 and HMC3-CD4, rat CHME-5 and mouse BV2 microglial lines plus primary monocyte-derived microglia-like cells.
- Determine whether blocking tankyrase, a PARP-family protein that restrains Hippo signaling, is the mechanism by which PARP inhibitors unlock the full latency-reversing capacity of HDAC inhibitors.
- Measure whether the drug combination also acts as a shield, lowering reactive oxygen species and inflammatory cytokines in microglial models while natural killer cells clear reactivated infected cells.
- Quantify brain and blood reservoir size, microglial activation and neuroinflammation after short-course PARP plus HDAC inhibitor treatment in EcoHIV-infected mice, using qRT-PCR, flow cytometry and fluorescence microscopy.
- Link reservoir reduction to functional benefit by pairing molecular and biochemical assays with behavioral tests of learning and memory in treated EcoHIV mice.
More about the research
These hidden copies are hard to remove, and the chronic inflammation and oxidative stress they drive damage the connections between neurons. Work in this lab asks whether two classes of already-approved drugs can be combined to flush the virus out of these brain reservoirs while simultaneously shielding brain cells from the damage that flushing causes.
Why it matters
People living with HIV now have near-normal lifespans but remain at high risk of lasting memory and thinking problems, and no therapy clears virus hiding in the brain. By repurposing two classes of already-approved cancer drugs, this work could point toward a treatment that both shrinks hidden viral reservoirs in the brain and periphery and protects neurons from inflammation and oxidative damage, potentially preserving long-term cognitive health.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Angela Raquel Wahl
University of Alabama at Birmingham, AL·Microbiology & Immunology
Analyze how the HIV reservoir forms in the gastrointestinal tract of BLT humanized mice on antiretroviral therapy, measuring HIV DNA and transcripts in gut CD4+ T cells compared with blood.
Wenhui Hu
Virginia Commonwealth University, VA·Microbiology & Immunology
Show that brain-penetrating AAV can deliver cargo to astrocytes and neurons that then relay it to untouched microglia, using PEG10- and syncytin-A-based endogenous retrovirus-like particles carrying Cre messenger RNA in LoxP-STOP-LoxP tdTomato reporter mice that turn red when edited.
Subhash Chand
University of Nebraska Medical Center, NE·Pharmacology
Test whether cannabidiol (CBD) reduces NLRP3 inflammasome activation, a key inflammation switch, in human monocyte-derived microglia exposed to HIV and methamphetamine, measuring gene expression from RNA and protein.
The school
American University: 2 labs on PI Pages, $78M a year on research, 84 research doctorates a year.
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