Joe GN Garcia

Joe GN Garcia

Professor, Medicine
Professor, Internal Medicine
Professor, Pharmacology and Toxicology
Professor, Physiology
Professor, Physiological Sciences - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
(520) 626-3151

Work Summary

The Garcia laboratory works to understand the molecular mechanisms of lung inflammatory processes, particularly those producing lung edema or vascular leak. The laboratory focus is to investigate gene discovery, protein function assessment, SNP discovery, genetic manipulation, in vivo testing, and candidate gene and biomarker identification, working to translate basic research into potential novel clinical therapies.

Research Interest

Dr. Garcia is an authority on the genetic basis of inflammatory lung disease (with an emphasis on health disparities) and on the mechanistic basis of lung vascular permeability. Using bench-to-bedside approaches, his lab has explored novel methods to prevent vascular leak and to restore endothelial cell barrier function and vascular integrity. This expertise in lung inflammation and vascular permeability provides a natural linkage to interrogation of lung vascular contribution to the development of lung metastases. Leveraging their genomic expertise, in recent years, Dr. Garcia's lab has identified vascular genes whose products are key participants in inflammatory lung injury that also play a role in cancer development. They have developed lung endothelial inflammatory gene expression profiles as well as diagnostic gene signatures influenced by MYLK and NAMPT that impact lung and breast cancer prognosis. This work with NAMPT led to development of a therapeutic NAMPT neutralizing antibody that has shown promise in treating lung cancer, melanoma, and chronic lymphocytic leukemia. Finally, Dr. Garcia's lab is also interested in the untoward effect of thoracic radiation and has been examining strategies designed to attenuate radiation–induced pneumonits, fibrosis and vascular leak. These collaborative and highly translational cancer research efforts have bolstered the overall mission of the University of Arizona Cancer Center.


Desai, A., Choi, B., Dudley, S. C., Garcia, J. G., Kittles, R. A., Lussier, Y. A., Machado, R. F., Patel, A. R., Lang, R. M., Goonewardena, S., Zhou, T., Parikh, D. S., Kansal, M., Hilery, C., Christensen, J., Shi, G., Indik, J. H., Strom, J., Juneman, E., , Groth, J., et al. (2017). IL-18 mediates sickle cell cardiomyopathy and inducible ventricular arrhythmias. PNAS.
Hecker, L., Garcia, J. G., Wang, T., Colson, B., Knox, A., Mohamed, M., Quijada, H., Desai, A., Ahmad, K., Shin, Y. J., & Palumbo, S. (2017). Dysregulated Nox4 ubiquitination contributes to redox imbalance and age-related severity of acute lung injury. American journal of physiology. Lung cellular and molecular physiology, 312(3), L297-L308.

Acute respiratory distress syndrome (ARDS) is a devastating critical illness disproportionately affecting the elderly population, with both higher incidence and mortality. The integrity of the lung endothelial cell (EC) monolayer is critical for preservation of lung function. However, mechanisms mediating EC barrier regulation in the context of aging remain unclear. We assessed the severity of acute lung injury (ALI) in young (2 mo) and aged (18 mo) mice using a two-hit preclinical model. Compared with young cohorts, aged mice exhibited increased ALI severity, with greater vascular permeability characterized by elevated albumin influx and levels of bronchoalveolar lavage (BAL) cells (neutrophils) and protein. Aged/injured mice also demonstrated elevated levels of reactive oxygen species (ROS) in the BAL, which was associated with upregulation of the ROS-generating enzyme, Nox4. We evaluated the role of aging in human lung EC barrier regulation utilizing a cellular model of replicative senescence. Senescent EC populations were defined by increases in β-galactosidase activity and p16 levels. In response to lipopolysaccharide (LPS) challenge, senescent ECs demonstrate exacerbated permeability responses compared with control "young" ECs. LPS challenge led to a rapid induction of Nox4 expression in both control and senescent ECs, which was posttranslationally mediated via the proteasome/ubiquitin system. However, senescent ECs demonstrated deficient Nox4 ubiquitination, resulting in sustained expression of Nox4 and alterations in cellular redox homeostasis. Pharmacological inhibition of Nox4 in senescent ECs reduced LPS-induced alterations in permeability. These studies provide insight into the roles of Nox4/senescence in EC barrier responses and offer a mechanistic link to the increased incidence and mortality of ARDS associated with aging.

Garcia, J. G., Garcia, J. G., Garcia, J. G., Garcia, J. G., Gonzalez-Garay, M. L., Gonzalez-Garay, M. L., Gonzalez-Garay, M. L., Gonzalez-Garay, M. L., Knox, K. S., Knox, K. S., Knox, K. S., Knox, K. S., Wang, T., Wang, T., Wang, T., Wang, T., Lussier, Y. A., Lussier, Y. A., Lussier, Y. A., , Lussier, Y. A., et al. (2018). MicroRNA and Protein-Coding Gene Expression Analysis in Idiopathic Pulmonary Fibrosis Yields Novel Biomarker Signatures Predicting Survival. American Journal of Respiratory Cell and Molecular Biology.
Rizzo, A. N., Sun, X., Letsiou, E., Garcia, J. G., & Dudek, S. M. (2016). Abl Family Kinases Mediate LPS-Induced Lung Vascular Permeability And Inflammation. Am J Respir Crit Care Med. doi:193: A5675
Desai, A., Rischard, F., Yuan, J., Black, S., Garcia, J. G., Whitaker, M., Dherange, P., Nair, V., & Natarajan, B. (2017). Hispanic disparities in pulmonary arterial hypertension. Circulation Heart Failure..