Jeremy Tran

All Publications

• Fluorescein-based SynNotch adaptors for regulating gene expression responses to diverse extracellular and matrix-based cues NATURE COMMUNICATIONS Tran, J. C., Kuffner, C. J., Marzilli, A. M., Miller, R., Silfen, Z. E., Mcmahan, J. B., Sloas, D., Chen, C. S., Ngo, J. T. 2025; 16 (1): 852

  Abstract

  Synthetic Notch (SynNotch) receptors function like natural Notch proteins and can be used to install customized sense-and-respond capabilities into mammalian cells. Here, we introduce an adaptor-based strategy for regulating SynNotch activity via fluorescein isomers and analogs. Using an optimized fluorescein-binding SynNotch receptor, we describe ways to chemically control SynNotch signaling, including an approach based on a bio-orthogonal chemical ligation and a spatially controllable strategy via the photo-patterned uncaging of an o-nitrobenzyl-caged fluorescein conjugate. We further show that fluorescein-conjugated extracellular matrix (ECM)-binding peptides can be used to regulate SynNotch activity depending on the folding state of collagen-based ECM networks. To demonstrate the utility of these tools, we apply them to activate dose-dependent gene expression responses and to induce myogenic-like phenotypes in multipotent fibroblasts with spatiotemporal and microenvironmental control. Overall, we introduce an optimized fluorescein-binding SynNotch as a versatile tool for regulating transcriptional responses to ligands based on the clinically-approved fluorescein dye.

  View details for DOI 10.1038/s41467-025-56148-7

  View details for Web of Science ID 001402014900012

  View details for PubMedID 39833147

  View details for PubMedCentralID PMC11756391

• Tension-tuned receptors for synthetic mechanotransduction and intercellular force detection NATURE BIOTECHNOLOGY Sloas, D., Tran, J. C., Marzilli, A. M., Ngo, J. T. 2023; 41 (9): 1287-+

  Abstract

  Cells interpret mechanical stimuli from their environments and neighbors, but the ability to engineer customized mechanosensing capabilities has remained a synthetic and mechanobiology challenge. Here we introduce tension-tuned synthetic Notch (SynNotch) receptors to convert extracellular and intercellular forces into specifiable gene expression changes. By elevating the tension requirements of SynNotch activation, in combination with structure-guided mutagenesis, we designed a set of receptors with mechanical sensitivities spanning the physiologically relevant picoNewton range. Cells expressing these receptors can distinguish between varying tensile forces and respond by enacting customizable transcriptional programs. We applied these tools to design a decision-making circuit, through which fibroblasts differentiate into myoblasts upon stimulation with distinct tension magnitudes. We also characterize cell-generated forces transmitted between cells during Notch signaling. Overall, this work provides insight into how mechanically induced changes in protein structure can be used to transduce physical forces into biochemical signals. The system should facilitate the further programming and dissection of force-related phenomena in biological systems.

  View details for DOI 10.1038/s41587-022-01638-y

  View details for Web of Science ID 000916896300001

  View details for PubMedID 36646932

  View details for PubMedCentralID PMC10499187