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Williamson, L. M.

Publications and source records attributed to Williamson, L. M..

2 recordsLinked to original sources

Oxygen-generating cryogel vaccines help overcome tumor antigen tolerance and induce durable anti-tumor immunity in prostate cancer

Therapeutic cancer vaccines represent a promising approach to boost patients own immune system to fight cancer. However, many vaccine candidates have shown limited success in clinical trials in large part due to the insufficient antigen delivery to overcome tolerance and hypoxia mediated immunosuppressive mechanisms. Cryogel-based delivery scaffolds have emerged as a promising platform for cancer vaccines due to their biocompatibility and macroporous structure that allows for effective delivery to infiltrating antigen-presenting cells. However, these systems are limited by rapid, diffusion-mediated burst release of encapsulated recombinant proteins and local hypoxia-driven immunosuppression within the scaffold. Herein, we demonstrate that click conjugation of a tumor-associated protein within cryogel-based vaccines, combined with our new O2-generating platform (Click O2-CryogelVAX), helps overcome immune suppression and weak antigenicity and primes effective anti-cancer immune responses. Sustained antigen delivery promotes cellular memory and Th1-mediated anti-cancer responses. By reversing hypoxia-driven immunosuppression, O2 acts as a powerful co-adjuvant to enhance humoral immunity. Together, Click O2-CryogelVAX supports a robust antitumor response that inhibits tumor growth and prolongs survival in a therapeutic prostate cancer model. These findings support the further research and development of Click O2-CryogelVAX as an effective delivery platform for therapeutic cancer vaccines.

bioengineering↗

Sound-seeking before and after hearing loss in mice

How we move our bodies affects how we perceive sound. For instance, we can explore an environment to seek out the source of a sound and we can use head movements to compensate for hearing loss. How we do this is not well understood because many auditory experiments are designed to limit head and body movements. To study the role of movement in hearing, we developed a behavioral task called sound-seeking that rewarded mice for tracking down an ongoing sound source. Over the course of learning, mice more efficiently navigated to the sound. We then asked how auditory behavior was affected by hearing loss induced by surgical removal of the malleus from the middle ear. An innate behavior, the auditory startle response, was abolished by bilateral hearing loss and unaffected by unilateral hearing loss. Similarly, performance on the sound-seeking task drastically declined after bilateral hearing loss and did not recover. In striking contrast, mice with unilateral hearing loss were only transiently impaired on sound-seeking; over a recovery period of about a week, they regained high levels of performance, increasingly reliant on a different spatial sampling strategy. Thus, even in the face of permanent unilateral damage to the peripheral auditory system, mice recover their ability to perform a naturalistic sound-seeking task. This paradigm provides an opportunity to examine how body movement enables better hearing and resilient adaptation to sensory deprivation.

animal behavior and cognition↗