Chemical pathology

Our laboratory studies cellular and tissue injury due to oxidative stress. We pioneered the discovery that cells surviving oxidative stress develop hypertrophy. This discovery has been validated in many cell types as a consequence of cellular stress and survival response. Enlarged cells contribute to loss of functionality during the development of diseases. In the myocardium, cardiomyocyte hypertrophy can be detected as a result of ischemic injury and contributes to heart failure. Continuing on the investigation of mechanisms of cell survival has led us to focus on cellular defense system. From our many years of comprehensive and systematic studies on cellular and molecular events initiated by oxidative stress, Nrf2 stands out as the key controller for cell defenses. We have made several discoveries in recent years, including 1) oxidative stress induced de novo Nrf2 protein translation; 2) Nrf2 physically interacts with mitochondria and protects mitochondria against oxidative stress induced decay; and 3) deficiency in Nrf2 sensitizes the myocardium to ischemic injury.

Yann C. Klimentidis, PhD, is an Associate Professor in the Department of Epidemiology and Biostatistics in the Mel and Enid Zuckerman College of Public Health at the University of Arizona. His research centers on improving our understanding of the links between genetic variation, lifestyle factors, metabolic disease, and health disparities. In the past, he has used measures of genetic admixture and genomic tests of natural selection to understand the genetic basis of population differences in disease susceptibility. His most recent work examines the use various statistical approaches for the analysis of high-dimensional genetic data for improving prediction of genetic susceptibility to type-2 diabetes. In addition, his work examines gene-by-lifestyle interactions in type-2 diabetes, as well as understanding the causal links between metabolic traits such as dyslipidemia and type-2 diabetes. Keywords: Genetics, epidemiology, Cardiometabolic disease, Physical activity

Chengcheng Hu, Ph.D., is an Associate Professor, Public Health and Director, Biostatistics, Phoenix campus at the Mel and Enid Zuckerman College of Public Health, University of Arizona. He is also Director of the Biometry Core on the Chemoprevention of Skin Cancer Project at the University of Arizona Cancer Center. Hu has worked on multiple federal grants in a broad range of areas including cancer, occupational health, HIV/AIDS, and aging. In addition to extensive experience in collaborative research, he has conducted methodological research in the areas of survival analysis, longitudinal data, high-dimensional data, and measurement error. His current methodological interest, arising from studies of viral and human genetics and biomarkers, is to develop innovative methods to investigate the relationship between high-dimensional information and longitudinal outcomes or survival endpoints. Hu joined the UA Mel and Enid Zuckerman College of Public Health in 2008. Prior to this he was an assistant professor of Biostatistics at the Harvard School of Public Health from 2002 to 2008. While at Harvard, he also served as senior statistician in the Pediatric AIDS Clinical Trials Group (PACTG) and the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT). Hu received his Ph.D. and M.S. in Biostatistics from the University of Washington and a M.A. in Mathematics from the Johns Hopkins University.

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.