Engineering precision through systematic design principles and iterative development methodology
Our design philosophy for TRACER is to create living, programmable cells that act as precise sentinels, silent under normal conditions but instantly responsive when they detect true signs of cancer. We treat sensing, processing, and responding as an integrated circuit rather than separate steps, ensuring that the same engineered cell can both report a threat and begin to counter it. Every component is chosen and tuned for modularity, scalability, and safety, so the proof-of-concept we build today can evolve into a clinically relevant theranostic platform without losing its precision or reliability.
Pioneering synthetic biology and advanced biosensing technologies for ultra-early, non-invasive cancer relapse detection through innovative biomarker engineering.
Synthetic biology approach programming immune cells with logic-based circuits
https://news.mit.edu/2025/equipping-living-cells-with-logic-gates-fighting-cancer-0418CD147/EMMPRIN functions: MMP induction, VEGF-mediated angiogenesis, and MCT1/4 metabolic regulation
https://doi.org/10.1038/srep32804Role of CD147 in the development and diagnosis of hepatocellular carcinoma. Front Immunol.
https://doi.org/10.3389/fimmu.2023.1149931Cancer-related issues of CD147. Cancer Genomics Proteomics. 2010 May-Jun;7(3):157-69. PMID: 20551248.
CD147 (Basigin) knockout uncouples MCT1/4, disrupting lactate export and tumor energetics
https://pubmed.ncbi.nlm.nih.govEMMPRIN regulates leukocyte trafficking into CNS via MMP activity, and is an Ig-superfamily protein with roles in MMP induction & leukocyte activation
https://doi.org/10.1523/JNEUROSCI.3659-10.2011CD147–hyaluronan axis: CD147 stimulates hyaluronan synthesis; links to cancer stemness, invasiveness, and chemoresistance
https://doi.org/10.1002/ar.24147Meta-analysis across cancers: high CD147 correlates with worse overall and disease-free survival
https://doi.org/10.1155/2015/242437Phase II trial in HCC: adjuvant ¹³¹I-metuximab improved 5-year recurrence-free survival post-hepatectomy (43% vs 22%)
https://doi.org/10.1016/S2468-1253(19)30422-4Phase IV study: ¹³¹I-metuximab + TACE versus TACE alone in advanced HCC, showing higher 1-year survival and longer time to progression with combination therapy
https://doi.org/10.7314/apjcp.2015.16.17.7441Engineering Customized Cell Sensing and Response Programs Using Synthetic Notch Receptors. Cell, 2016;164(4):780-791. PMC.
https://doi.org/10.1016/j.cell.2016.01.012Precision Tumor Recognition by T Cells With Combinatorial Antigen-Sensing Circuits. Cell, 2016;164(4):770-779.
https://doi.org/10.1016/j.cell.2016.09.011Engineering of an enhanced synthetic Notch receptor by reducing ligand-independent activation. Communications Biology, 2020;3:116.
https://doi.org/10.1038/s42003-020-0848-xRecent advances in synthetic Notch receptors for biomedical applications. American Journal of Physiology-Cell Physiology, 2025 (advance).
https://doi.org/10.1152/ajpcell.00659.2024Functional Comparison between Endogenous and Synthetic Notch Receptors in Mammalian Cells. ACS Synthetic Biology, 2022. PMC.
https://doi.org/10.1021/acssynbio.2c00247Engineering an αCD206-synNotch Receptor: Insights into Modular Receptor Design. ACS Synthetic Biology, 2024.
https://doi.org/10.1021/acssynbio.4c00149Engineering programmable material-to-cell pathways via synNotch activation by ECM-derived ligands. Nature Communications, 2024;15: 1-14.
https://doi.org/10.1038/s41467-024-50126-1Enhancement of cell-specific transgene expression from a Tet-Off system. BMC Molecular Biology, 2008. PMC.
https://doi.org/10.1002/jgm.1178A tunable dual-input system for on-demand dynamic gene regulation combining Tet system and protein destabilization. Nature Communications, 2019.
https://doi.org/10.1038/s41467-019-12329-9Inducible, tightly regulated and non-leaky gene expression in mice using Tet-Off systems. Transgenic Research, 2014;23(2):225-233.
https://doi.org/10.1007/s11248-013-9767-7DNA-binding of the Tet-transactivator curtails antigen-specific responses: lessons from the TRE-tight system. Nature Communications, 2017.
https://doi.org/10.1038/s41467-017-01022-4Introduction to Tet expression systems (overview of Tet-Off, Tet-On designs, tTA/TRE mechanism)
https://www.jax.orgGaussia luciferase reporter assay for monitoring biological processes in culture and in vivo. Nature Protocols, 4(4), 582–591.
https://doi.org/10.1038/nprot.2009.28Secreted Gaussia luciferase as a biomarker for monitoring tumor progression and treatment response of systemic metastases. PLoS ONE, 4(12), e8316.
https://doi.org/10.1371/journal.pone.0008316A secreted luciferase for ex vivo monitoring of in vivo processes. Nature Methods, 5(2), 171–177.
https://doi.org/10.1038/nmeth.1177Reporter gene comparison demonstrates interference of secreted Gaussia luciferase in complex body fluids. Scientific Reports, 11, 991.
https://doi.org/10.1038/s41598-020-80451-6Advanced bioluminescence reporter with engineered Gaussia luciferase. Biosensors, 14(11), 528.
https://doi.org/10.3390/bios14110528Rational design of an anti-cancer peptide inhibiting CD147/CypA interaction. Frontiers in Oncology, 12, 947951.
https://doi.org/10.3389/fonc.2022.947951CD147: An integral and potential molecule to abrogate in cancer. Frontiers in Oncology, 13, 1238051.
https://doi.org/10.3389/fonc.2023.1238051CD147 antibodies and CD147-CAR T cells. World Intellectual Property Organization.
https://patents.google.com/patent/WO2023000170A1/en