Education & Training
- Sc.B., Biomedical Engineering, Brown University, 2007
- Ph.D., Molecular Genetics and Microbiology, Harvard University, 2013
- Postdoc, Immunology, University of Pittsburgh, 2018
Research Interest Summary
The general focus of my lab is using synthetic biology approaches to genetically reprogram immune cells to treat disease. Immune cells are an ideal chassis for therapeutic intervention as they are involved in the prevention or pathology of nearly every major disease, they can be genetically manipulated, and they have the capability of migrating to and affecting most locations in the body. Engineering cells with synthetic protein receptors and gene circuits, we are aiming to overcome current barriers to successful adoptive T cell therapy, especially for solid tumors, including: immune inhibitory signals of the disease micro-environment, cell-intrinsic limits to T cell persistence and function, and developing new antigen targeting strategies to avoid toxicities and relapse. One key technology that we are developing is “universal” SNAP adaptor CAR T cells and synthetic Notch (synNotch) T cells that can be targeted to any cell surface antigen of interest by co-administered antibodies, allowing the same engineered T cells to be used to target multiple antigens in a patient or across patients. We are now working on translating this approach to the clinic through characterization in pre-clinical animal models. An exciting extension of this work is creating conditional ON and OFF-switches to get even more specific targeting of solid tumor cells using these receptors. Another major project area is applying synthetic biology to re-wire immune cell signaling pathways to respond to novel inputs such as small molecule drugs and soluble proteins and the engineering of artificial cell-cell communication. Our standard experimental system for developing all of these technologies is viral engineering of primary human T cells followed by functional characterization by flow cytometry and high-content fluorescence imaging in vitro as well as in vivo testing in pre-clinical humanized tumor xenograft mouse models.
Kataoka S, Manandhar P, Lee J, Workman CJ, Banerjee H, Szymczak-Workman AL, Kvorjak M, Lohmueller J, Kane LP. The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse. Sci Signal. 2021 Jun 15;14(687), PMID: 34131021.
Lohmueller J, Butchy AA, Tivon Y, Kvorjak M, Miskov-Zivanov N, Deiters A, Finn OJ. Post-translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting. bioRxiv. 2020 January; doi: 10.1101/2020.01.17.909895.
Lohmueller J, Ham JD, Kvorjak M, Finn OJ. mSA2 affinity-enhanced biotin-binding CAR T cells for universal tumor targeting. Oncoimmunology. 2017; 7(1):e1368604. PMID: 29296519.
Lohmueller J, Finn OJ. Current modalities in cancer immunotherapy: immunomodulatory antibodies, CARs, and vaccines. Review. Pharmacology & Therapeutics. 2017 Oct;178:31-47. PMID: 28322974
Lohmueller J, Sato S, Popova L, Chu IM, Tucker MA, Barberena R, Innocenti GM, Cudic M, Ham JD, Cheung WC, Polakiewicz RD, Finn OJ. Antibodies elicited by the first non-viral prophylactic cancer vaccine show tumor-specificity and immunotherapeutic potential. Sci Rep. 2016 Aug 22;6:31740. PMID: 27545199
Lienert F, Lohmueller J, Garg A, Silver PA. Synthetic biology in mammalian cells: Next generation genetic research tools and therapeutics. Nature Reviews Molecular Cell Biology. 2014 Feb;15(2):95-107. PMID: 24434884
Selgrade DF*, Lohmueller J*, Lienert F, Silver PA. Protein scaffold-activated protein trans-splicing in mammalian cells. J Am Chem Soc. 2013 May 22;135(20):7713-9. PMID: 23621664. *Contributed equally
Garg A*, Lohmueller J*, Silver PA, Armel TZ. Engineering synthetic TAL effectors with orthogonal target sites. Nucleic Acids Res. 2012 Aug;40(15):7584-95. PMID: 22581776.*Contributed equally
Lohmueller J, Armel TZ, Silver PA. A tunable zinc finger-based framework for Boolean logic computation in mammalian cells. Nucleic Acids Res. 2012 Jun;40(11):5180-7. PMID: 22323524.