Jessica Stark

About My Research

Glycoconjugates – biopolymers decorated with sugars, or glycans – coat the surface of every cell and provide one of the first points of contact with the immune system. Alteration of the chemical structures of appended glycans is often associated with disease and can contribute to pathogenesis by modulating immune responses. Thus, glycoconjugates represent attractive targets for immunotherapy, with broad potential applications for the treatment of infectious disease, cancer, and autoimmunity. However, a key challenge that has historically limited our ability to study or therapeutically target interactions between glycoconjugates and immune cells is the non-templated nature of the glycosylation process. For instance, a single glycoprotein is composed of a collection of different glycoforms bearing distinct glycan structures, which arise due to the stochastic action of multiple glycosylation enzymes in living cells. This inherent heterogeneity presents barriers to studying or targeting the specific glycoforms that play immunomodulatory roles. To address this limitation, I developed a synthetic biological technology for rapid and facile enzymatic synthesis of glycoproteins bearing homogeneous glycan structures. I further applied this technology to enable on-demand and portable production of glycoconjugate vaccines that use bacterial cell-surface glycans to educate immune cells to respond to infections. My current work focuses on identifying and targeting specific glycoforms that allow cancer cells to evade anti-tumor immune responses. Overall, my new technologies and approaches promise to help elucidate the roles of glycoconjugates in disease and enable development of new therapeutic interventions.

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