- Research Assistant Professor, Medicine
- Ph.D. Clinical Translationa Sciences
- University of Arizona, Tucson, Arizona, United States
- MOLECULAR STRATEGIES TO DISTINGUISH KEY SUBPHENOTYPES IN SARCOIDOSIS
- MPH Public Health
- Benedictine University, Lisle, Illinois, United States
- M.D. Medicine
- Universidad Autonoma de Aguascalientes, Aguascalientes, Mexico
- Clinical Translational Sciences Travel Award
- University of Arizona, Summer 2019
- Clinical Translational Sciences Travel Award.
- CTS Graduate Program, Summer 2018
Licensure & Certification
- Medical Graduate, Educational Commission for Foreign Medical Graduates (2009)
ClinicalResearch. Interstitial Lung diseases/ Sarcoidosis.
No activities entered.
- Casanova, N. (2016). Health Disparities in Respiratory Medicine. New York: Humana Press. doi:10.1007/978-3-319-23675-9
- Bime, C., & Casanova, N. (2019). Development of a biomarker mortality risk model in acute respiratory distress syndrome. Critical Care, 23(410). doi:doi:10.1186/s13054-019-2697-x
- Casanova, N., Zhou, T., Garcia, J. G., & Gonzalez-Garay, M. L. (2019). Low Dose Carbon Monoxide Exposure in Idiopathic Pulmonary Fibrosis Produces a CO Signature Comprised of Oxidative Phosphorylation Genes. Scientific Reports. doi:10.1038/s41598-019-50585-3.More infoWe recently reported the results of a multicenter, double-blinded, clinical trial of inhaled CO in patients with idiopathic pulmonary fibrosis (IPF). Despite modest increases in CO blood levels, low dose CO exposure failed to demonstrate a significant effect on the primary study endpoint of changes in serum metalloproteinase-7 (MMP7), or secondary endpoints of physiologic measures, hospitalization, death, or patient-reported outcomes. In the present study, we evaluated the effect of CO exposure (12 week treatment) on genome-wide gene expression in peripheral blood mononuclear cells (PBMC) derived from these IPF study subjects.We identified a clear CO signature dominated by significant dysregulation of genes in the oxidative phosphorylation pathway. These findings suggest this signature may serve as a potential genomic biomarker for CO exposure and perhaps for titration of dosage to allow precision testing of therapies in future low dose CO therapeutic studies in IPF.
- Lynn, H., Sun, X., Casanova, N., Gonzales-Garay, M., Bime, C., & Garcia, J. G. (2019). Genomic and Genetic Approaches to Deciphering Acute Respiratory Distress Syndrome Risk and Mortality. Antioxidants & redox signaling, 31(14), 1027-1052.More infoAcute respiratory distress syndrome (ARDS) is a severe, highly heterogeneous critical illness with staggering mortality that is influenced by environmental factors, such as mechanical ventilation, and genetic factors. Significant unmet needs in ARDS are addressing the paucity of validated predictive biomarkers for ARDS risk and susceptibility that hamper the conduct of successful clinical trials in ARDS and the complete absence of novel disease-modifying therapeutic strategies. The current ARDS definition relies on clinical characteristics that fail to capture the diversity of disease pathology, severity, and mortality risk. We undertook a comprehensive survey of the available ARDS literature to identify genes and genetic variants (candidate gene and limited genome-wide association study approaches) implicated in susceptibility to developing ARDS in hopes of uncovering novel biomarkers for ARDS risk and mortality and potentially novel therapeutic targets in ARDS. We further attempted to address the well-known health disparities that exist in susceptibility to and mortality from ARDS. Bioinformatic analyses identified 201 ARDS candidate genes with pathway analysis indicating a strong predominance in key evolutionarily conserved inflammatory pathways, including reactive oxygen species, innate immunity-related inflammation, and endothelial vascular signaling pathways. Future studies employing a system biology approach that combines clinical characteristics, genomics, transcriptomics, and proteomics may allow for a better definition of biologically relevant pathways and genotype-phenotype connections and result in improved strategies for the sub-phenotyping of diverse ARDS patients molecular signatures. These efforts should facilitate the potential for successful clinical trials in ARDS and yield a better fundamental understanding of ARDS pathobiology.
- Bime, C., Bime, C., Pouladi, N., Pouladi, N., Sammani, S., Sammani, S., Batai, K., Batai, K., Casanova, N., Casanova, N., Zhou, T., Zhou, T., Kempf, C., & Kempf, C. (2018). GWAS in African Americans identifies the Selectin P Ligand gene, SELPLG, as an ARDS risk gene. American J Respiratory Critical Care Medicine.
- Lynn, H. D., Lynn, H. D., Sun, X., Sun, X., Ayshiev, D., Ayshiev, D., Karnes, J. H., Karnes, J. H., Gonzalez-Garay, M. L., Gonzalez-Garay, M. L., Casanova, N., Casanova, N., Wang, T., Wang, T., Garcia, J. G., Garcia, J. G., Siegler, J. H., & Siegler, J. H. (2018). Single nucleotide polymorphisms (SNPs) in the MYLKP1 pseudogene are associated with increased colon cancer risk in African Americans. PLOS ONE, 13, 13(8):e0200916.
- Lynn, H. D., Sun, X., Ayshiev, D., Karnes, J. H., Gonzalez-Garay, M. L., Casanova, N., Wang, T., Garcia, J. G., & Siegler, J. H. (2018). Single nucleotide polymorphisms (SNPs) in the MYLKP1 pseudogene are associated with increased colon cancer risk in African Americans. PLOS ONE.More infoWe previously reported that MYLKP1, the pseudogene of MYLK that encodes myosin light chain kinase (MLCK), is highly expressed in lung and colon cancer cell lines and tissues but not in normal lung or colon. The MYLKP1 promoter is minimally active in normal bronchial epithelial cells but highly active in lung adenocarcinoma cells. In this study, we further validate MYLKP1 as an oncogene via elucidation of the functional role of MYLKP1 genetic variants in colon cancer risk
- Siegler, J. H., Garcia, J. G., Wang, T., Casanova, N., Gonzalez-Garay, M. L., Karnes, J. H., Ayshiev, D., Sun, X., & Lynn, H. D. (2018). Single nucleotide polymorphisms (SNPs) in the MYLKP1 pseudogene are associated with increased colon cancer risk in African Americans. PLOS ONE.
- Zhou, T., Casanova, N., Pouladi, N., Wang, T., Lussier, Y., Knox, K. S., & Garcia, J. G. (2017). Identification of Jak-STAT signaling involvement in sarcoidosis severity via a novel microRNA-regulated peripheral blood mononuclear cell gene signature. Scientific reports, 7(1), 4237.More infoSarcoidosis is a granulomatous lung disorder of unknown cause. The majority of individuals with sarcoidosis spontaneously achieve full remission (uncomplicated sarcoidosis), however, ~20% of sarcoidosis-affected individuals experience progressive lung disease or cardiac and nervous system involvement (complicated sarcoidosis). We investigated peripheral blood mononuclear cell (PBMC) microRNA and protein-coding gene expression data from healthy controls and patients with uncomplicated or complicated sarcoidosis. We identified 46 microRNAs and 1,559 genes that were differentially expressed across a continuum of sarcoidosis severity (healthy control → uncomplicated sarcoidosis → complicated sarcoidosis). A total of 19 microRNA-mRNA regulatory pairs were identified within these deregulated microRNAs and mRNAs, which consisted of 17 unique protein-coding genes yielding a 17-gene signature. Pathway analysis of the 17-gene signature revealed Jak-STAT signaling pathway as the most significantly represented pathway. A severity score was assigned to each patient based on the expression of the 17-gene signature and a significant increasing trend in the severity score was observed from healthy control, to uncomplicated sarcoidosis, and finally to complicated sarcoidosis. In addition, this microRNA-regulated gene signature differentiates sarcoidosis patients from healthy controls in independent validation cohorts. Our study suggests that PBMC gene expression is useful in diagnosis of sarcoidosis.
- Singla, S., Zhou, T., Javaid, K., Abbasi, T., Casanova, N., Zhang, W., Ma, S. F., Wade, M. S., Noth, I., Sweiss, N. J., Garcia, J. G., & Machado, R. F. (2016). Expression profiling elucidates a molecular gene signature for pulmonary hypertension in sarcoidosis. Pulmonary circulation, 6(4), 465-471.More infoPulmonary hypertension (PH), when it complicates sarcoidosis, carries a poor prognosis, in part because it is difficult to detect early in patients with worsening respiratory symptoms. Pathogenesis of sarcoidosis occurs via incompletely characterized mechanisms that are distinct from the mechanisms of pulmonary vascular remodeling well known to occur in conjunction with other chronic lung diseases. To address the need for a biomarker to aid in early detection as well as the gap in knowledge regarding the mechanisms of PH in sarcoidosis, we used genome-wide peripheral blood gene expression analysis and identified an 18-gene signature capable of distinguishing sarcoidosis patients with PH (n = 8), sarcoidosis patients without PH (n = 17), and healthy controls (n = 45). The discriminative accuracy of this 18-gene signature was 100% in separating sarcoidosis patients with PH from those without it. If validated in a large replicate cohort, this signature could potentially be used as a diagnostic molecular biomarker for sarcoidosis-associated PH.
- Casanova, N., Zhou, T., Knox, K. S., & Garcia, J. G. (2015). Identifying Novel Biomarkers in Sarcoidosis Using Genome-Based Approaches. Clinics in chest medicine, 36(4), 621-30.More infoThis article briefly reviews conventional biomarkers used clinically to (1) support a diagnosis and (2) monitor disease progression in patients with sarcoidosis. Potential new biomarkers identified by genome-wide screening and the approaches to discover these biomarkers are described.
- Siegler, J. H., Lynn, H. D., Garcia, J. G., Sun, X., Ayshiev, D., Wang, T., Casanova, N., Karnes, J. H., Gonzalez-Garay, M. L., Gonzalez-Garay, M. L., Karnes, J. H., Casanova, N., Ayshiev, D., Wang, T., Sun, X., Garcia, J. G., Siegler, J. H., & Lynn, H. D. (2018). Single nucleotide polymorphisms (SNPs) in the MYLKP1 pseudogene are associated with increased colon cancer risk in African Americans. PLOS ONE.More infoWe previously reported that MYLKP1, the pseudogene of MYLK that encodes myosin light chain kinase (MLCK), is highly expressed in lung and colon cancer cell lines and tissues but not in normal lung or colon. The MYLKP1 promoter is minimally active in normal bronchial epithelial cells but highly active in lung adenocarcinoma cells. In this study, we further validate MYLKP1 as an oncogene via elucidation of the functional role of MYLKP1 genetic variants in colon cancer risk
- Strange, C., Senior, R. M., Sciurba, F., O'Neal, S., Morris, A., Wisniewski, S. R., Bowler, R., Hochheiser, H. S., Becich, M. J., Zhang, Y., Leader, J. K., Methé, B. A., Kaminski, N., Sandhaus, R. A., & , G. A. (2015). Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol. Annals of the American Thoracic Society, 12(10), 1551-60.More infoSevere deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis α1 Study is a prospective, multicenter, cross-sectional study of adults older than age 35 years with PiZZ or PiMZ alpha-1 antitrypsin genotypes. It is designed to better understand if microbial factors influence this heterogeneity. Clinical symptoms, pulmonary function testing, computed chest tomography, exercise capacity, and bronchoalveolar lavage (BAL) will be used to define chronic obstructive pulmonary disease (COPD) phenotypes that can be studied with an integrated systems biology approach that includes plasma proteomics; mouth, BAL, and stool microbiome and virome analysis; and blood microRNA and blood mononuclear cell RNA and DNA profiling. We will rely on global genome, transcriptome, proteome, and metabolome datasets. Matched cohorts of PiZZ participants on or off alpha-1 antitrypsin augmentation therapy, PiMZ participants not on augmentation therapy, and control participants from the Subpopulations and Intermediate Outcome Measures in COPD Study who match on FEV1 and age will be compared. In the primary analysis, we will determine if the PiZZ individuals on augmentation therapy have a difference in lower respiratory tract microbes identified compared with matched PiZZ individuals who are not on augmentation therapy. By characterizing the microbiome in alpha-1 antitrypsin deficiency (AATD), we hope to define new phenotypes of COPD that explain some of the diversity of clinical presentations. As a unique genetic cause of COPD, AATD may inform typical COPD pathogenesis, and better understanding of it may illuminate the complex interplay between environment and genetics. Although the biologic approaches are hypothesis generating, the results may lead to development of novel biomarkers, better understanding of COPD phenotypes, and development of novel diagnostic and therapeutic trials in AATD and COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01832220).
- Zhang, X., Zhang, W., Ma, S. F., Desai, A. A., Saraf, S., Miasniakova, G., Sergueeva, A., Ammosova, T., Xu, M., Nekhai, S., Abbasi, T., Casanova, N. G., Steinberg, M. H., Baldwin, C. T., Sebastiani, P., Prchal, J. T., Kittles, R., Garcia, J. G., Machado, R. F., & Gordeuk, V. R. (2014). Hypoxic response contributes to altered gene expression and precapillary pulmonary hypertension in patients with sickle cell disease. Circulation, 129(16), 1650-8.More infoWe postulated that the hypoxic response in sickle cell disease (SCD) contributes to altered gene expression and pulmonary hypertension, a complication associated with early mortality.
- Casanova, N., Gonzalez-Garay, M. L., Sun, B., Sun, X., & Garcia, J. G. (2019, May). Sarcoidosis And Coccidioidomycosis Share Common Tissue Transcriptome Expression Profiles. ATS International Conference. Dallas: American Thoracic Society.More infoIn this study we compared sarcoidosis gene expression profiles of lung and lymph node granulomas to tissues from patients with tuberculosis and coccidioidomycosis or Valley Fever (VF), a soil-dwelling fungi disease endemic in the southwest. We also aimed to compare sarcoidosis tissue gene expression to our previous gene signatures derived from peripheral blood mononuclear (PBMC). Incorporation of precise approaches like molecular biomarkers in the differential diagnosis will facilitate and expedite the diagnosis.
- Berghout, J., Casanova, N., Lussier, Y. A., Gonzalez-Garay, M. L., Pouladi, N., Navarrete, J., Garcia, J. G., Knox, K. S., Knox, K. S., Garcia, J. G., Pouladi, N., Navarrete, J., Gonzalez-Garay, M. L., Lussier, Y. A., Casanova, N., & Berghout, J. (2017, May). TNF-α specific PBMC responses in complicated and uncomplicated sarcoidosis by RNA-Seq. American Thoracic Society International Conference. Washington DC: ATS.
- Berghout, J., Lussier, Y. A., Navarrete, J., Garcia, J. G., Knox, K. S., Pouladi, N., Gonzalez-Garay, M. L., & Casanova, N. (2017, May). TNF-α specific PBMC responses in complicated and uncomplicated sarcoidosis by RNA-Seq. American Thoracic Society International Conference. Washington DC: ATS.
- Casanova, N., Gonzalez-Garay, M. L., Knox, K. S., & Garcia, J. G. (2017, April). Identifying responsive TNF-α transcripts in complicated Sarcoidosis. PRIDE Annual Meeting. Bethesda, MD: NIH.More infoPrograms to Increase Diversity Among Individuals Engaged in Health-Related Research (PRIDE).
- Casanova, N., Zhou, T., Knox, K. S., & Garcia, J. G. (2016, May). Peripheral Blood MicroRNA Signature Differentiates Sarcoidosis. American Thoracic Society International Conference. San Francisco: ATS.