Dayanne Carvalho

All Publications

• Activation-induced SLC7A1 expression enhances T cell sensitivity to cGAMP-mediated STING signaling. Cell reports Sudaryo, V., Carvalho, D. R., Carozza, J. A., Cao, X., Kernick, C., Cordova, A. F., Lee, J. M., Roth, T. L., Li, L. 2026; 45 (7): 117580

  Abstract

  STING (stimulator of interferon genes) agonists are promising innate immune therapies and can be synergized with adaptive immune checkpoint blockade therapies for cancer treatment, but their effectiveness is limited by the toxicity to activated T cells. How STING agonists such as cGAMP and its analogs enter and induce STING activation and toxicity in T cells is unclear despite known transporters for other cell types. Here, we identify the cationic amino acid transporter SLC7A1 as a cGAMP transporter in activated primary mouse and human T cells. T cells upregulate this transporter upon activation to meet their high metabolic demand, but this comes at the cost of enabling increased transport and toxicity of cGAMP. We identified distinct residues in SLC7A1 that mediate cGAMP and arginine activity, suggesting that cGAMP transport may be separable from arginine uptake. These findings suggest that modulation of SLC7A1 may influence T cell susceptibility to cGAMP and its analogs.

  View details for DOI 10.1016/j.celrep.2026.117580

  View details for PubMedID 42329763

• Stereochemical Control Yields Mucin Mimetic Polymers ACS CENTRAL SCIENCE Kruger, A. G., Brucks, S. D., Yan, T., Carcarmo-Oyarce, G., Wei, Y., Wen, D. H., Carvalho, D. R., Hore, M. J. A., Ribbeck, K., Schrock, R. R., Kiessling, L. L. 2021; 7 (4): 624-630

  Abstract

  All animals except sponges produce mucus. Across the animal kingdom, this hydrogel mediates surface wetting, viscosity, and protection against microbes. The primary components of mucus hydrogels are mucins-high molecular weight O-glycoproteins that adopt extended linear structures. Glycosylation is integral to mucin function, but other characteristics that give rise to their advantageous biological activities are unknown. We postulated that the extended conformation of mucins is critical for their ability to block microbial virulence phenotypes. To test this hypothesis, we developed synthetic mucin mimics that recapitulate the dense display of glycans and morphology of mucin. We varied the catalyst in a ring-opening metathesis polymerization (ROMP) to generate substituted norbornene-derived glycopolymers containing either cis- or trans-alkenes. Conformational analysis of the polymers based on allylic strain suggested that cis- rather than trans-poly(norbornene) glycopolymers would adopt linear structures that mimic mucins. High-resolution atomic force micrographs of our polymers and natively purified Muc2, Muc5AC, and Muc5B mucins revealed that cis-polymers adopt extended, mucin-like structures. The cis-polymers retained this structure in solution and were more water-soluble than their trans-analogs. Consistent with mucin's linear morphology, cis-glycopolymers were more potent binders of a bacterial virulence factor, cholera toxin. Our findings highlight the importance of the polymer backbone in mucin surrogate design and underscore the significance of the extended mucin backbone for inhibiting virulence.

  View details for DOI 10.1021/acscentsci.0c01569

  View details for Web of Science ID 000645561800012

  View details for PubMedID 34056092

  View details for PubMedCentralID PMC8155468

• Modern approaches towards the synthesis of geminal difluoroalkyl groups ORGANIC & BIOMOLECULAR CHEMISTRY Carvalho, D. R., Christian, A. H. 2021; 19 (5): 947-964

  Abstract

  This review will cover the importance of and most recent approaches toward geminal difluoroalkyl groups. Transition metal-mediated, photochemical, organocatalytic, and other methods as well as their mechanistic implications will be discussed, with special emphasis on applications to biologically-relevant compounds.

  View details for DOI 10.1039/d0ob02374d

  View details for Web of Science ID 000617008600002

  View details for PubMedID 33406177