Bioengineering Seminars

The 2025-2026 Distinguished Lecture in Bioengineering

Wednesday, November 12
4:00 -5:00 PM
105 Stanley Hall

“Molecular Engineering to Tip Immune Balances between Tolerance and Aggression”

Jeffrey A Hubbell, PhD
Vice President Life Sciences and Engineering
Professor of Chemical and Biomolecular Engineering, Tandon School of Engineering
Professor of Biology and Chemistry, Faculty of Arts and Sciences
Professor of Biochemistry and Molecular Pharmacology, NYU Langone Health
New York University

Abstract:
We explore materials and protein engineering approaches to deliver antigens and cytokines to tip the immune balance between tolerance and aggression. In the context of tolerance, induction of regulatory T cells is critical, and antigen specificity can arise from exogenously administered antigens in the form of an inverse vaccine or from endogenous antigens in a site of inflammation. In either case, we explore methods to induce or deliver cytokines to regions of lymph nodes where immunity develops and is regulated. In recent work in allergic asthma, we developed an approach employing glycosylated polymers to deliver allergic antigens and induce regulatory cytokine expression to re-bias immunity back to tolerance, inducing allergen-specific regulatory T cells and thus preventing asthmatic responses to pulmonary antigen challenge. In work in an experimental model of autoimmune neuroinflammation, we are developing an approach to deliver the tolerogenic cytokine IL-10 to all the secondary lymphoid organs of the body from a simple subcutaneous administration. Here, antigen specific Tregs were developed in response to myelin antigens that drain from the inflammation site. In the context of aggression, we have developed an approach to deposit inflammatory cytokines in the tumor microenvironment to tip the balance between cytotoxic T lymphocytes and Tregs, whether by agonizing innate immune cells such as macrophages and dendritic cells or adaptive immune cells, in particular T cells. With regard to antigens in mounting immune aggression, we have developed cysteine-reactive polymers that bind in situ to the surfaces of tumor cells to direct the adduct to antigen-presenting cells along with polymer-conjugated adjuvant moieties to induce an anti-tumoral vaccine response. Thus, in both contexts, biological functionality can be engineered to guide immunity toward tolerance in inflammation, allergy and autoimmunity and toward aggression in cancer.