Weinberger and colleagues discovered the HIV latency circuit (Weinberger* et al. Cell 2005), which provided the first experimental evidence that stochastic fluctuations (‘noise’) in gene expression drive biological fate decisions. Noise-driven decisions were then found in systems ranging from bacteria to cancer. The lab's studies overturned dogma in the field by showing that HIV latency was a ‘hardwired’ virus program (Razooky et al. Cell 2015; Rouzine et al. Cell 2015) and discovered stochastic latency programs in other viruses (Chaturvedi et al. PNAS 2020). For these contributions, Weinberger received the NIH Avant-Garde award for HIV research and an NIH Merit Award.
The lab discovered noise-enhancer molecules (Dar et al. Science 2014), now used by numerous other labs—e.g., to modulate circadian rhythms (Li et al. PNAS 2020)—and discovered a cellular noise-control pathway that potentiates embryonic cell-fate transitions (Desai et al. Science 2021). These studies demonstrated that transcriptional noise can be a ‘feature not a bug’ of cellular systems and play a functional, physiological role.
On the therapeutic front, the lab conceptualized and forwarded Therapeutic Interfering Particles (TIPs) (Weinberger et al. J Virol. 2003)—a first-in-class antiviral countermeasure that is single-dose and escape-resistant (see TED talk, below). The lab's initial work led to the DARPA INTERCEPT program (a $40M initiative that funded dozens of virology labs worldwide from 2015–20). In 2020, the lab discovered TIPs for SARS-CoV-2 (Chaturvedi et al. Cell 2021)—the first TIP reported for any virus—and provided long-sought evidence for the therapeutic effect of the TIP mechanism of action. Following FDA reviews, the DoD and NIH funded TIP clinical trials for HIV and SARS-CoV-2.
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