Daniel Jose Navarrete

All Publications

• Spatiotemporal-social association predicts immunological similarity in rewilded mice. Science advances Downie, A. E., Oyesola, O., Barre, R. S., Caudron, Q., Chen, Y. H., Dennis, E. J., Garnier, R., Kiwanuka, K., Menezes, A., Navarrete, D. J., Mondragón-Palomino, O., Saunders, J. B., Tokita, C. K., Zaldana, K., Cadwell, K., Loke, P., Graham, A. L. 2023; 9 (51): eadh8310

  Abstract

  Environmental influences on immune phenotypes are well-documented, but our understanding of which elements of the environment affect immune systems, and how, remains vague. Behaviors, including socializing with others, are central to an individual's interaction with its environment. We therefore tracked behavior of rewilded laboratory mice of three inbred strains in outdoor enclosures and examined contributions of behavior, including associations measured from spatiotemporal co-occurrences, to immune phenotypes. We found extensive variation in individual and social behavior among and within mouse strains upon rewilding. In addition, we found that the more associated two individuals were, the more similar their immune phenotypes were. Spatiotemporal association was particularly predictive of similar memory T and B cell profiles and was more influential than sibling relationships or shared infection status. These results highlight the importance of shared spatiotemporal activity patterns and/or social networks for immune phenotype and suggest potential immunological correlates of social life.

  View details for DOI 10.1126/sciadv.adh8310

  View details for PubMedID 38134275

  View details for PubMedCentralID PMC10745690

• Metabolic profiling during malaria reveals the role of the aryl hydrocarbon receptor in regulating kidney injury. eLife Lissner, M. M., Cumnock, K., Davis, N. M., Vilches-Moure, J. G., Basak, P., Navarrete, D. J., Allen, J. A., Schneider, D. 2020; 9

  Abstract

  Systemic metabolic reprogramming induced by infection exerts profound, pathogen-specific effects on infection outcome. Here, we detail the host immune and metabolic response during sickness and recovery in a mouse model of malaria. We describe extensive alterations in metabolism during acute infection, and identify increases in host-derived metabolites that signal through the aryl hydrocarbon receptor (AHR), a transcription factor with immunomodulatory functions. We find that Ahr-/- mice are more susceptible to malaria and develop high plasma heme and acute kidney injury. This phenotype is dependent on AHR in Tek-expressing radioresistant cells. Our findings identify a role for AHR in limiting tissue damage during malaria. Furthermore, this work demonstrates the critical role of host metabolism in surviving infection.

  View details for DOI 10.7554/eLife.60165

  View details for PubMedID 33021470

• Therapeutic breast reconstruction using gene therapy delivered IFN-gamma immunotherapy. Molecular cancer therapeutics Davis, C. R., Than, P. A., Khong, S. M., Rodrigues, M., Findlay, M. W., Navarrete, D. J., Ghali, S., Vaidya, J. S., Gurtner, G. C. 2019

  Abstract

  After mastectomy, breast reconstruction is increasingly performed using autologous tissue with the aim of improving quality of life. During this procedure, autologous tissue is excised, relocated, and reattached using vascular anastomoses at the site of the extirpated breast. The period during which the tissue is ex vivo may allow genetic modification without any systemic exposure to the vector. Could such access be used to deliver therapeutic agents using the tissue flap as a vehicle? Such delivery may be more efficient than systemic treatment, in terms of oncological outcomes. The cytokine interferon gamma (IFNgamma) has antitumor effects, but systemic toxicity that could be circumvented if its effect can be localized by delivery of the IFNgamma gene via gene therapy to autologous tissue used for breast reconstruction, which then releases IFNgamma and exerts anti-tumor effects. In a rat model of loco-regional recurrence (LRR) using both MADB-106-Luc and MAD-MB-231-Luc breast cancer cells, autologous tissue was transduced ex vivo with an adeno-associated viral vector (AAV) encoding IFNgamma. The therapeutic reconstruction released IFNgamma at the LRR site and eliminated cancer cells, significantly decreased tumor burden (P<0.05), and increased survival by 33% (P<0.05) compared to sham reconstruction. Mechanistically, localized IFNgamma immunotherapy stimulated M1 macrophages to target cancer cells within the regional confines of the modified tumor environment. This concept of therapeutic breast reconstruction using ex vivo gene therapy of autologous tissue offers a new application for immunotherapy in breast cancer with a dual therapeutic effect of both reconstructing the ablative defect and delivering local adjuvant immunotherapy.

  View details for DOI 10.1158/1535-7163.MCT-19-0315

  View details for PubMedID 31658961