van Oosten-Hawle Lab
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Our Research
Aging is a fundamental biological process. But its pace can be shaped by how organisms respond to stress. A striking example is hormesis: the phenomenon in which mild, transient stress activates protective stress response mechanisms that improve cellular function and can extend lifespan. Research in the van Oosten-Hawle Lab aims to understand how these stress response mechanisms influence the aging process and human age-associated disease. We focus on how these stress response pathways are coordinated between tissues in a multicellular organism to activate protein quality-control programs cell nonautonomously. By dissecting how signals from specific tissues coordinate systemic stress defenses, we aim to uncover principles and targets for maintaining proteome integrity during aging.
The Stress Paradox, Organismal Proteostasis and Longevity
Low-level challenges, such as brief heat or cold exposure, act like “training sessions” for the body, strengthening stress resistance networks and supporting long-term health by activating protective protein quality control mechanisms that maintain protein homeostasis (proteostasis) in all cells of an organism.
In multicellular organisms, these benefits depend on organism-wide coordination, not just the cells that directly sense stress. Stress responses are transmitted between tissues through cell nonautonomous signaling, allowing one tissue to trigger protein quality-control and stress-defense pathways in others. This project aims to understand how the nervous system, intestine, and other organs play central roles in this cross-tissue communication, collectively re-establishing organismal proteostasis and protecting organismal health during aging.
Transcellular Chaperone Signaling & Organismal Functions of Hsp90
A central theme of our lab is to define how Hsp90 regulates organismal stress responses. Specifically, how does Hsp90-dependent signaling integrate tissue-specific stress states into a coordinated, system-wide response? This is not a coincidence: Hsp90 is an essential molecular chaperone that stabilizes and controls a wide range of “client” proteins required for cellular signaling, including the HSF1-mediated heat shock response.
In earlier work, we discovered that changing Hsp90 levels in a single tissue can activate protein quality control programs in distant tissues. We named this long-range communication "Transcellular Chaperone Signaling," which reduces age-associated protein aggregation and boosts stress resilience across the organism. We are now dissecting the mechanisms underlying this phenomenon to understand how local proteostasis states are sensed, transmitted, and translated into protective systemic adaptations within the organism, using C. elegans as a model system.
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Stress Responsive Transcription Factors
A fascinating stress-responsive transcription factor is the zinc-finger transcription factor PQM-1. It is a key regulator of organismal proteostasis and we previously identified its role in cross-tissue stress signaling. Our lab is investigating how PQM-1 is activated in adulthood to enhance stress resilience and promote longevity. We also explore how PQM-1 works alongside other major proteostasis transcription factors, including HSF-1 and DAF-16, to coordinate systemic stress defenses and maintain cellular health during aging.