My research program is underpinned by the concept that genes do not exist nor function in isolation, they work together in networks. My lab employs network graph theory and computational systems biology to work backwards (reverse engineering) from genomic profiles of immune cells to reconstruct the wiring diagram of the underlying molecular networks. The long-term goal of this work is to unlock the fundamental principles that govern the functionality of the immune system in healthy versus disease states, unveiling actionable targets for therapeutic intervention. Towards this goal, I have developed a Translational Systems Immunology research program at the Telethon Kids Institute, which brings together clinicians, basic scientists, and systems biology in a complimentary way to accelerate bench-to-bedside research. The research program has a strong focus on translation. It builds capacity in genomic data science, and fosters the development of strong linkages between researchers, clinicians, and industry.
My lab specializes in employing systems biology approaches to identify novel cellular and molecular mechanisms underlying asthma and related traits. For example, we performed the first studies to identify rhinovirus-induced gene network patterns that underpin the pathogenesis of asthma and related traits. We have investigated these gene networks in children and in experimental animal models across multiple anatomical locations (upper airways, lower airways, blood, bone marrow). We discovered that exacerbation responses in children are heterogeneous and are characterized by airway IRF7hi versus IRF7lo molecular phenotypes, and further that the airway responses comprised two major gene network structures centered around IRF7/IFN and FCER1G. We also demonstrated that IRF7 phenotypes can be observed in an experimental rat model contrasting strains manifesting high susceptibility (BN/IRF7lo) versus low susceptibility (IRF7lo) to experimental asthma. Notably, the presence or absence of IRF7 gene networks in the rat model was mirrored in the lung and bone marrow, suggesting our hypothesis that IRF7 gene networks operate locally in the airways and systematically through a lung-blood-bone marrow axis. Finally, we have evaluated the utility of administration of bacterial lysate immunotherapy (OM85) in a rat model of experimental asthma and in high-risk infants for protection against severe lower respiratory tract infections. We found that OM85 treatment dampens pro-inflammatory responses and boosts innate immunity. Overall, our findings have led to novel insights into the pathogenesis of virus-induced asthma exacerbations and new approaches to treatment and/or prevention.
Our Vision - To build a systems immunobiology program that accelerates bench-to-bedside research and focuses on the early origins of disease.
What we do - The Systems Biology laboratory at UArizona’s Asthma & Airway Disease Research Center combines expert domain knowledge in immunobiology with the powerful tools of systems biology to obtain mechanistic insight into the role of the immune system in the pathogenesis of asthma.
Our approach - The research program is divided into three distinct phases: (i) Basic discovery Science; (ii) Translational Science; (iii) Venture Development.
The long-term Impact! - The long-term goal of this work is to unlock the molecular secrets that govern the early origins of asthma and develop new approaches to predict disease development and avoid disease transition.
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