(2du) Engineering (Glyco)Immunology

My long-term research vision seeks to understand and engineer the immune response to sugars, or glycans. Immunoengineering promises to yield the next generation of therapies for unmet medical needs in infectious disease, autoimmunity, and cancer. However, a key challenge facing the field is our limited understanding of how the immune system recognizes and responds to glycoconjugates. Glycoconjugates – biomolecules decorated with sugars, or glycans – coat the surface of every cell. As a result, all of molecular immunology involves or is influenced by glycoconjugates. For example, glycoconjugates regulate immune cell trafficking, modulate immune cell activation, and represent molecular patterns that define self and non-self. The chemical structures of appended glycans are often altered in disease states and can contribute to pathogenesis by modulating immune responses. Thus, glycoconjugates represent a vast set of attractive, yet mostly untapped, disease-specific antigens and targets for immunotherapy.

My independent research group will address gaps in knowledge and technology that have historically limited our ability to profile and perturb immunomodulatory glycoconjugates. We will pursue three primary research directions: 1) engineer molecular platforms to study and therapeutically target disease-associated glycan antigens, 2) develop technologies to profile cell surface glycosylation with single cell resolution, and 3) apply tools generated in the first two research thrusts to elucidate mechanisms of innate and adaptive anti-glycan immunity. We will use interdisciplinary approaches, integrating biomolecular and cellular engineering, synthetic and systems biology, glycoscience, and immunology in order to achieve these goals. Together, this work promises to reveal new insights into how sugars regulate the immune system, with immediate applications for development of next-generation immunotherapies.

Research Experience

My doctoral and postdoctoral training have prepared me to lead this research program. As an NSF Graduate Research Fellow with Prof. Michael Jewett at Northwestern University, I established a new method for glycoconjugate vaccine synthesis that promises to accelerate novel vaccine development and increase access through refrigeration-independent distribution and portable production (Stark & Jaroentomeechai, et al. Sci Adv 2021). I further developed a platform for rapid biosynthesis of proteins bearing user-specified glycosylation, which will facilitate investigation of their immunomodulatory properties (Jaroentomeechai & Stark, et al. Nat Commun 2018). As an American Cancer Society Postdoctoral Fellow with Prof. Carolyn Bertozzi at Stanford University, I am developing new approaches to identify and target glycan-based immune checkpoints for cancer immunotherapy. Specifically, I am developing antibody-lectin bispecifics for blockade of glyco-immune checkpoints in cancer (Stark & Gray, et al. in prep). The bispecific platform is modular and can be applied to diverse disease- or cell type-specific antigens and lectin (glycan-binding) immunoreceptors. In parallel, I developed an interaction proteomics pipeline to define tumor-associated glycoconjugates that engage inhibitory glycan-binding immunoreceptors called Siglecs. This approach has resulted in the identification of previously unknown tumor-associated glycoconjugate antigens that represent targets for cancer immunotherapy (Stark, et al. in prep). Collectively, my work has helped elucidate the roles of immunomodulatory glycans and glycoconjugates in disease and promises to accelerate development of new vaccines and immunotherapies.

Complete list of my published work: tinyurl.com/2s49hv9f

Teaching Interests & Experience

As a chemical engineer by training, I am excited to teach core undergraduate courses. In particular, I have experience as a co-instructor for the chemical engineering separations course at Northwestern University. I am further enthusiastic about the opportunity to teach or develop graduate level courses related to my research interests and expertise. As examples, I have previously developed and given lectures for courses in synthetic biology, biomolecular engineering, and drug development.

Commitment to Diversity, Equity, and Inclusion

Diverse perspectives accelerate scientific progress and innovation. As a result, enhancing diversity, equity, and inclusion (DEI) in STEM is essential. I am working to increase DEI by developing and implementing 1) inclusive teaching strategies, 2) impactful outreach programs, and 3) effective community building initiatives. Together, my efforts seek to both recruit and retain students from underrepresented groups in STEM. I developed and commercialized BioBits® educational kits to increase access to high-quality biology education by democratizing hands-on learning. I have executed multiple successful community outreach events with organizations such as the Society of Hispanic Professional Engineers, Boys Hope Girls Hope, and Chicago public schools. I currently serve on the Stanford Chemistry Equity and Inclusion committee, where I am leading development of a new REU program and facilitating implementation of a preview day for prospective graduate students from diverse backgrounds. Both events seek to create cohort and community among students from underrepresented groups in the chemistry department at Stanford. As an independent investigator, I will seek to implement these initiatives in my home department and advocate for similar programs across my research organization. Most importantly, I will teach my trainees to be DEI activists through community outreach, mentorship, and education of the next generation of diverse scientists and engineers.