Klinik für Allgemein- und Viszeralchirurgie

Research

Our goal is the develop therapies that can effectively and safely control the immune system to rescue patients from life-threatening diseases. In cancer, for example, tumor-induced immunosuppression is a major challenge to overcome for the development of effective immunotherapies. On the other hand, controlled immunosuppression can be highly valuable in auto-immunity and regenerative medicine to prevent tissue degeneration or transplant rejection. Therefore, understanding how to precisely instruct immune responses toward immunosuppression or immune-rejection is a must to develop immunomodulatory biomaterials and therapeutics for the clinic.

Our research currently focuses on understanding the interactions between immune factors (e.g., cytokines) and the extracellular matrix to highlight key mechanisms by which the extracellular matrix modulates immune responses in colorectal cancer and melanoma. We then aim to engineer these interactions to develop new cancer immunotherapies and improve the clinical efficacy of current immune-checkpoint inhibitors. Besides, we will use this knowledge to mimic cancer-derived immunosuppression for regenerative medicine applications, to dampen unwanted chronic inflammation. Our translational approach relies on the use of biomaterials and protein engineering.

Positions

Our group is currently recruiting Master and MD students (full-time lab work for ~ 6 months and more). If you are interesting to join, please don’t hesitate to contact the group leader directly.

Key publications

• Gray LT, Raczy MM, Briquez PS, Marchell TM, Alpar AT, Wallace RP, Volpatti LR, Sasso MS, Cao S, Nguyen M, Mansurov A, Budina E, Watkins EA, Solanki A, Mitrousis N, Reda JW, Yu SS, Tremain AC, Wang R, Nicolaescu V, Furlong K, Dvorkin S, Manicassamy B, Randall G, Wilson DS, Kwissa M, Swartz MA, Hubbell JA. Generation of potent cellular and humoral immunity against SARS-CoV-2 antigens via conjugation to a polymeric glyco-adjuvant. Biomaterials. 2021 Nov;278:121159.

• Briquez PS, Tsai HM, Watkins EA, Hubbell JA. Engineered bridge protein with dual affinity for bone morphogenetic protein-2 and collagen enhances bone regeneration for spinal fusion. Sci Adv. 2021 Jun 11;7(24):eabh4302.

• Sasso MS, Mitrousis N, Wang Y, Briquez PS, Hauert S, Ishihara J, Hubbell JA, Swartz MA. Lymphangiogenesis-inducing vaccines elicit potent and long lasting T cell immunity against melanomas. Sci Adv 2021 Mar 24; 7(13):eabe4362.

• Briquez PS, Hauert S, de Titta A, Gray LT, Alpar AT, Swartz MA, Hubbell JA. Engineering Targeting Materials for Therapeutic Cancer Vaccines. Front Bioeng Biotechnol. 2020 Feb 11;8:19.

• Mochizuki M, Güç E, Park AJ, Julier Z, Briquez PS, Kuhn GA, Müller R, Swartz MA, Hubbell JA, Martino MM. Growth factors with enhanced syndecan binding generate tonic signalling and promote tissue healing. Nat Biomed Eng. 2020 Apr;4(4):463-475.

• Briquez PS, Lorentz KM, Larsson HM, Frey P, Hubbell JA. Human Kunitz-type protease inhibitor engineered for enhanced matrix retention extends longevity of fibrin biomaterials. Biomaterials. 2017 Aug;135:1-9.

• Briquez PS, Clegg LE, Martino MM, Mac Gabhann F, Hubbell JA.  Design principles for therapeutic angiogenic materials. Nat Rev Mater. 2016 Jan; 1, 15006.

• Martino MM, Briquez PS, Güç E, Tortelli F, Kilarski WW, Metzger S, Rice JJ, Kuhn GA, Müller R, Swartz MA, Hubbell JA. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science. 2014 Feb 21;343(6173):885-8.   

• Martino MM, Briquez PS, Ranga A, Lutolf MP, Hubbell JA. Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. Proc Natl Acad Sci USA. 2013 Mar 19;110(12):4563-8.