Robert Foronjy, MD

Over the past twenty years, my research greatly expanded the understanding of the basic mechanisms of emphysema and smoke-related lung diseases. Under the tutelage of my mentor Dr. Jeanine D’Armiento, I demonstrated for the first time that enhanced lung expression of collagenase induced adult-onset emphysematous and lung compliance changes in mice. This changed the disease paradigm by establishing that emphysema could occur through mechanisms independent of elastin degradation. Using the cigarette smoke exposure model, which I pioneered at Columbia University Medical Center, we showed that enhanced antioxidant expression in the lung prevented smoke-induced inflammation and airspace enlargement in mice. It had long been established that oxidative injury was enhanced in COPD and this was the first study to show that countering this injury could prevent the development of COPD features in mice. My research group then conducted further studies to identify the mechanisms by which antioxidant expression protected against smoke-induced lung injury. Our studies found that glutathione peroxidase-1 (GPX-1) counters emphysema by acting via protein tyrosine phosphatase 1B (PTP1B) to increase protein phosphatase 2A (PP2A) activity in the lung. Subsequent studies determined that GPX-1 is down regulated in the airways in COPD and this could explain the enhanced susceptibility to smoke-mediated lung damage in these subjects. Working with the HIV researcher Dr. David Volsky, I established a model of HIV-related COPD in mice. This model reproduces the physiologic and anatomic changes that occur in HIV related smokers. The use of this model promises to provide key mechanistic insights into the pathogenesis of HIV related COPD. More recently, our research group investigated the role of the RNA binding protein HuR in the pathogenesis of COPD. We aim to show that HuR is a critical determinant of antioxidant mRNA stability in the lung. These studies could lead to therapeutic approaches that target HuR to increase the lung’s antioxidant defenses.