Jeremy Luban
University of Massachusetts Chan Medical School, MA·Microbiology & Immunology
Antiretroviral drugs can push HIV-1 down to undetectable levels in the blood, yet they do not cure the infection. The reason is that the virus inserts a DNA copy of itself, called a provirus, into the chromosomes of long-lived memory CD4+ T cells, the immune cells HIV infects.
- Fields
Microbiology & Immunology
Genetics
Biochemistry
- Topics
HIV latency
provirus
HUSH complex
- Grants
- 1 known grant, through May 2029
What they work on
- Identify host factors required for HUSH-mediated silencing of the HIV-1 provirus using unbiased genome-wide loss-of-function screens, then test mechanistic hypotheses for how each factor contributes.
- Map the cellular proteins located near HUSH-silenced proviruses using C-BERST, a dCas9-APEX2 fusion directed to the provirus by guide RNAs.
- Test whether candidate silencing factors sustain latency in people, by disrupting the genes in stimulated CD4+ T cells from people living with HIV-1 on antiretroviral therapy and quantifying cell-associated HIV-1 RNA.
- Define the cis-acting determinants of HUSH sensitivity by engineering promoters and transcripts of HUSH-targeted proviruses and transgenes, and ask whether HUSH exerts selective pressure on HIV-1 sequences cloned from infected people.
- Measure how HUSH shapes the chromatin landscape of primary CD4+ T cells using RNA-Seq, ATAC-Seq and CUT&Tag, including its effects on endogenous retroviruses embedded in the human genome.
- Knock out HUSH components in human CD34+ hematopoietic stem cells and use them to reconstitute a model immune system, assessing CD4+ T cell development and the effect on HIV-1 replication and latency establishment.
More about the research
Most of those proviruses sit silent: they make no RNA, so neither drugs nor the immune system can find the cells harboring them. Understanding what keeps proviruses switched off, and what could switch them on, is central to any strategy for clearing the virus from the body.
Why it matters
Current HIV-1 drugs prevent AIDS but cannot eliminate the silent proviruses hidden in memory CD4+ T cells. By defining how the HUSH complex keeps these proviruses quiet and what happens to T cells when HUSH is removed, this work could inform cure strategies that force latent virus to reveal itself so that drugs or the immune system can clear it, while flagging the risks such an intervention might carry for immune cell development.
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.
James Whitney
Boston College, MA·Microbiology & Immunology
Determine how early the persistent viral reservoir is established after SIV infection and how initiating antiretroviral therapy early limits seeding and expansion of cellular reservoirs.
The school
University of Massachusetts Chan Medical School: 29 labs on PI Pages, $350M a year on research, 55 research doctorates a year.
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