Hubbell Lab

Our laboratory develops molecular and materials engineering approaches in immunotherapy, focused on vaccination in infectious disease and cancer and on an antigen-specific tolerance induction to protein drugs, allergens and autoimmune antigens.

Nanomaterials in adjuvant and antigen delivery

Induction of adaptive immune responses to defined protein antigens, referred to as subunit vaccination, is relatively effective in generation of humoral immunity to create neutralizing antibodies but is less effective in generating cytotoxic T lymphocytes that can kill chronically-infected cells or cancer cells. We develop protein engineering and materials engineering approaches to address this lack. We work on nanomaterials that can simultaneously carry antigen and adjuvant biomolecules to dendritic cells that are resident in the lymph nodes that drain an injection site, engineering both the anatomical and sub-cellular delivery sites so as to maximize exogenous antigen presentation on MHC I and resulting induction of CD8+ T cell responses, working in both infectious disease and cancer models. We also develop nanomaterials to carry adjuvant biomolecules into tumors to modulate the tumor immune microenvironment to shape anti-tumor immunity. We develop novel nanomaterial carriers that are in the 25-50 nm regime due to their ability to penetrate interstitial barriers after injection and the tumor vasculature after intravenous administration. Thus, we both study tumor immunophysiology and develop novel interventions with the intention to tip the balance of immunity toward an anti-tumor response.

Protein and materials engineering in tolerogenic antigen delivery

Technologies to induce antigen-specific immunological tolerance are still in their infancy but are needed to prevent immunity to many protein drugs, to reverse immunity to allergens, and to prevent and reverse immunity to autoimmune antigens. We develop protein and materials engineering approaches to deliver antigens so as to induce antigen-specific tolerance, sometimes referred to as inverse vaccination. On the one hand, we investigate basic mechanisms of peripheral tolerance, how self-antigens are cleared from apoptotic cell debris, for example, in the spleen and especially the liver, to understand the mechanisms by which the body remains establishes and maintains tolerance to ageing cells and proteins. We use that understanding to develop technological approaches by which to deliver exogenous antigens so as to induce antigen-specific tolerance, using both protein engineering methods for delivery and materials engineering approaches to target antigen to particular tolerogenic cell populations. We work in models of immunity to protein drugs (for example, proteins that are not of human origin or are congenitally lacking in the subject), to protein allergens, and to autoimmune antigens (with a focus on type 1 diabetes models).

 

Principal Investigator

Jeffrey Hubbell

jhubbell@uchicago.edu

Our research spans biology, chemistry, and engineering in order to generate novel solutions to common health problems. We are mainly affiliated with the Pritzker School of Molecular Engineering at UChicago, though we have strong connections to biomedical engineering, chemistry, and immunology. Our three main focuses are: tissue remodeling, drug delivery, and immunological tolerance. Each of these topics aim to tackle current problems facing millions of people around the world. Our ground-up approach begins with a deep understanding of the problem being addressed and the current state of knowledge in that field, followed by development of creative solutions and rigorous testing.

Our laboratory consists of project scientists, post-docs, technicians, grad students, and undergrads working in a team-based setting that facilitates immersion and discussion of the issues at hand. Our state-of-the-art equipment and facility allows for efficient data gathering and the generation of novel compounds. Working in close collaboration with other Principle Investigators, such as Melody Schwartz and Jun Huang, fosters strong collaboration and grants access to further possibitlies outside of our immediate group. 

Through our research and protein engineering we hope to make impactful discoveries that can be translated into the clinic to make a tangible improvement in human health.

Adaptive enhanced sampling by force-biasing using neural networks

Guo, Ashley Z., et al. "Adaptive enhanced sampling by force-biasing using neural networks." The Journal of chemical physics 148.13 (2018): 134108.

Design principles for therapeutic angiogenic materials

P.S. Briquez, L.E. Clegg, M.M. Martino, F.M. Gabhann, J.A. Hubbell. Design principles for therapeutic angiogenic materials. Nature Reviews Materials. 2016. Vol. 1, Pg. 15006.

Crystalline Oligo Domains Define Highly Stable Supramolecular Block Copolymer Assemblies

C.E. Brubaker, D. Velluto, D. Demurtas, E.A. Phelps, J.A. Hubbell. Crystalline Oligo Domains Define Highly Stable Supramolecular Block Copolymer Assemblies. ACS Nano. 2015. Vol. 9, Pg. (7).

TLR4 Agonist Fibronectin Extra Domain A is Cryptic, Exposed by Elastase-2; use in a cancer vaccine

Z. Julier, M.M. Martino, A. de Titta, L. Jeanbart, J.A. Hubbell. TLR4 Agonist Fibronectin Extra Domain A is Cryptic, Exposed by Elastase-2; use in a cancer vaccine. Scientific Reports. 2015. Vol. 5, Pg. 8569.

Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in hous

M. Ballester, L. Jeanbart, A. de Titta, C. Nembrini, B.J. Marsland, J.A. Hubbell, M.A. Swartz. Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in hous. Science Reports. 2015. Vol. 5, Pg. 14274.

TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in

M. Damo, D.S. Wilson, E. Simeoni, J.A. Hubbell,. TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in. Scientific Reports. 2015. Vol. 5, Pg. 17622.

Engineered binding to erythrocytes induces immunological tolerance to E. coli asparaginase

K.M. Lorentz, S. Kontos, G. Diaceri, H. Henry, J.A. Hubbell. Engineered binding to erythrocytes induces immunological tolerance to E. coli asparaginase. Science Advances. 2015. Vol. 1, Pg. (6).

The TLR4 Agonist Fibronectin Extra Domain A; use in a fibrin matrix cancer vaccine

Z. Julier, M.M. Martino, A. de Titta, L. Jeanbart, J.A. Hubbell. The TLR4 Agonist Fibronectin Extra Domain A; use in a fibrin matrix cancer vaccine. Scientific Reports. 2015. Vol. 5, Pg. 8569.

Memory of tolerance and induction of regulatory T cells by erythrocyte-targeted antigens

A.J. Grimm, S. Kontos, G. Diaceri, X. Quaglia-Thermes, J.A. Hubbell. Memory of tolerance and induction of regulatory T cells by erythrocyte-targeted antigens. Scientific Reports. 2015. Vol. 5, Pg. 15907.

Fibrin gels engineered with pro-angiogenic growth factors promote engraftment of pancreatic islets

M. Najjar, V. Manzoli, M. Abreu, C. Villa, M.M. Martino, R.D. Molano, Y. Torrente, A. Pileggi, L. Inverardi, C. Ricordi, J.A. Hubbell, A.A. Tomei. Fibrin gels engineered with pro-angiogenic growth factors promote engraftment of pancreatic islets. Biotechnology and Bioengineering. 2015. Vol. 112, Pg. 1916–1926.

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