Fernando Martinez

Professor, Pediatrics

Director, Asthma / Airway Disease Research Center

Endowed Chair, Swift - McNear

Regents Professor

Professor, Genetics - GIDP

Professor, BIO5 Institute

Primary Department

Asthma & Airway Disease Research Center

Department Affiliations

Asthma & Airway Disease Research Center

BIO5 Institute

Contact

(520) 626-5954

fdmartin@arizona.edu

Research Interest

Dr. Fernando D. Martinez is a Regents’ Professor and Director of the Asthma & Airway Disease Research Center at the University of Arizona in Tucson. Dr. Martinez is a world-renowned expert, and one of the most highly regarded researchers, in the field of childhood asthma. His primary research interests are the natural history, genetics, and treatment of childhood asthma. His groundbreaking research has had an impact on his field in numerous ways, most prominent among them the development of the concept of the early origins of asthma and COPD. This concept is now widely accepted as the potential basis for the design of new strategies for the prevention of these devastating illnesses affecting millions of children and adults worldwide. In addition, Dr. Martinez has made important contributions to our understanding of the role of gene-environment interactions in the development of asthma and allergies. He has also been the principal investigator of one of the Clinical Centers that are part of the NHLBI Asthma Treatment Networks, which have contributed fundamental new evidence on which to base national guidelines for the treatment of the disease. Dr. Martinez currently serves on national scientific boards including the NHLBI National Advisory Council and the National Scientific Council on the Developing Child. He was a member of the National Asthma Education and Prevention Program that was responsible for the development of the Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma in 1997 and its first revision in 2001. He also has been a member of the FDA Pulmonary-Allergy Drugs Advisory Committee and the Board of Extramural Advisors of the National Heart, Lung, and Blood Institute (NHLBI). Dr. Martinez’s research and vision are well detailed in more than 250 original research papers and editorials, many in collaboration with investigators from all over the world. He is frequently invited to give keynote presentations at national and international meetings.

Publications

Prevalence of Asthma in School Children on the Arizona-Sonora Border

Carr, T. F., Beamer, P. I., Rothers, J., Stern, D. A., Gerald, L. B., Rosales, C. B., Van Horne, Y. O., Pivniouk, O. N., Vercelli, D., Halonen, M., Gameros, M., Martinez, F. D., & Wright, A. L. (2017). Prevalence of Asthma in School Children on the Arizona-Sonora Border. The journal of allergy and clinical immunology. In practice, 5(1), 114-120.e2.

BIO5 Collaborators

Paloma Beamer, Fernando Martinez

Mexican-born children living in the United States have a lower prevalence of asthma than other US children. Although children of Mexican descent near the Arizona (AZ)-Sonora border are genetically similar, differences in environmental exposures might result in differences in asthma prevalence across this region.

Bending the Twig Does the Tree Incline: Lung Function after Lower Respiratory Tract Illness in Infancy

Martinez, F. D. (2017). Bending the Twig Does the Tree Incline: Lung Function after Lower Respiratory Tract Illness in Infancy. American journal of respiratory and critical care medicine, 195(2), 154-155.

Early-Life Origins of Chronic Obstructive Pulmonary Disease

Martinez, F. D. (2016). Early-Life Origins of Chronic Obstructive Pulmonary Disease. The New England journal of medicine, 375(9), 871-8.

Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma

Igartua, C., Myers, R. A., Mathias, R. A., Pino-Yanes, M., Eng, C., Graves, P. E., Levin, A. M., Del-Rio-Navarro, B. E., Jackson, D. J., Livne, O. E., Rafaels, N., Edlund, C. K., Yang, J. J., Huntsman, S., Salam, M. T., Romieu, I., Mourad, R., Gern, J. E., Lemanske, R. F., , Wyss, A., et al. (2015). Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma. Nature communications, 6, 5965.

Common variants at many loci have been robustly associated with asthma but explain little of the overall genetic risk. Here we investigate the role of rare (1%) and low-frequency (1-5%) variants using the Illumina HumanExome BeadChip array in 4,794 asthma cases, 4,707 non-asthmatic controls and 590 case-parent trios representing European Americans, African Americans/African Caribbeans and Latinos. Our study reveals one low-frequency missense mutation in the GRASP gene that is associated with asthma in the Latino sample (P=4.31 × 10(-6); OR=1.25; MAF=1.21%) and two genes harbouring functional variants that are associated with asthma in a gene-based analysis: GSDMB at the 17q12-21 asthma locus in the Latino and combined samples (P=7.81 × 10(-8) and 4.09 × 10(-8), respectively) and MTHFR in the African ancestry sample (P=1.72 × 10(-6)). Our results suggest that associations with rare and low-frequency variants are ethnic specific and not likely to explain a significant proportion of the 'missing heritability' of asthma.

The metabolomics of asthma control: a promising link between genetics and disease

McGeachie, M. J., Dahlin, A., Qiu, W., Croteau-Chonka, D. C., Savage, J., Wu, A. C., Wan, E. S., Sordillo, J. E., Al-Garawi, A., Martinez, F. D., Strunk, R. C., Lemanske, R. F., Liu, A. H., Raby, B. A., Weiss, S., Clish, C. B., & Lasky-Su, J. A. (2015). The metabolomics of asthma control: a promising link between genetics and disease. Immunity, inflammation and disease, 3(3), 224-38.

Short-acting β agonists (e.g., albuterol) are the most commonly used medications for asthma, a disease that affects over 300 million people in the world. Metabolomic profiling of asthmatics taking β agonists presents a new and promising resource for identifying the molecular determinants of asthma control. The objective is to identify novel genetic and biochemical predictors of asthma control using an integrative "omics" approach. We generated lipidomic data by liquid chromatography tandem mass spectrometry (LC-MS), - using plasma samples from 20 individuals with asthma. The outcome of interest was a binary indicator of asthma control defined by the use of albuterol inhalers in the preceding week. We integrated metabolomic data with genome-wide genotype, gene expression, and methylation data of this cohort to identify genomic and molecular indicators of asthma control. A Conditional Gaussian Bayesian Network (CGBN) was generated using the strongest predictors from each of these analyses. Integrative and metabolic pathway over-representation analyses (ORA) identified enrichment of known biological pathways within the strongest molecular determinants. Of the 64 metabolites measured, 32 had known identities. The CGBN model based on four SNPs (rs9522789, rs7147228, rs2701423, rs759582) and two metabolites-monoHETE_0863 and sphingosine-1-phosphate (S1P) could predict asthma control with an AUC of 95%. Integrative ORA identified 17 significantly enriched pathways related to cellular immune response, interferon signaling, and cytokine-related signaling, for which arachidonic acid, PGE2 and S1P, in addition to six genes (CHN1, PRKCE, GNA12, OASL, OAS1, and IFIT3) appeared to drive the pathway results. Of these predictors, S1P, GNA12, and PRKCE were enriched in the results from integrative and metabolic ORAs. Through an integrative analysis of metabolomic, genomic, and methylation data from a small cohort of asthmatics, we implicate altered metabolic pathways, related to sphingolipid metabolism, in asthma control. These results provide insight into the pathophysiology of asthma control.

Fernando Martinez