Cancer immunotherapy has transformed treatment for many patients, but its long-term success is often limited by T cell exhaustion. Over time, cancer-fighting T cells lose their strength and ability to attack tumors, reducing the effectiveness of therapies such as checkpoint inhibitors and engineered T cell treatments.
Although scientists have identified many of the genetic signatures associated with exhausted T cells, far less is known about the proteins that actually control this dysfunctional state. Dr. Vinogradova aims to uncover these critical molecular regulators and identify new ways to restore durable immune responses.
Her project combines advanced chemical biology, proteomics, and functional genomics to systematically study thousands of proteins and protein sites that may influence T cell exhaustion. A key innovation is the development of a powerful new screening platform capable of testing more than 4,000 potential protein targets directly in human T cells.
By identifying proteins that can be selectively controlled with small molecules, Dr. Vinogradova hopes to develop highly targeted chemical tools that reactivate exhausted T cells without broadly overstimulating the immune system. The most promising compounds will then be tested in melanoma models to determine whether they improve anti-tumor immunity.
This work could create an entirely new framework for discovering cancer immunotherapy drugs and lead to next-generation treatments that help immune cells remain active longer, improving the durability and effectiveness of cancer immunotherapy.
Projects and Grants: A chemoproteogenomic platform to pharmacologically probe and modify T cell function
