Rama K. Mallampalli, MD
Research Interest: Mammalian phospholipid synthesis


Dr. Mallampalli's research is in the area of pulmonary epithelial molecular and cell biology as it relates to acute lung injury and the mechanisms of sepsis. The primary goal of his research is to investigate the molecular mechanisms for control of the major phospholipid of animal membranes and of lung surfactant, phosphatidylcholine (PC). PC levels are tightly controlled, in part, by the rate-regulatory phosphoenzyme cytidylyltransferase (CCT). His work investigates the molecular physiology of how CCT is controlled by reversible phosphorylation events within its carboxyl-terminus and its regulation by enzyme turnover. In models of inflammatory lung injury, surfactant PC biosynthesis is impaired because CCT activity decreases as a result of post-translational enzyme modification and gene transcriptional repression. Specifically, he has discovered that CCT is coordinately degraded by calpains and the ubiquitin system in models of pulmonary sepsis. These adverse effects are opposed by the calcium- sensor, calmodulin, that binds and stabilizes CCT during infection. Dr. Mallampalli's second area of research interest is in the molecular control of ubiquitin E3 ligases and how they might impact lipogenic proteins. His current activity investigates how calcium-regulated effectors control site-specific ubiquitination of target lung proteins (e.g. CCT) that in turn ultimately increase degradation of these substrates through proteasome-independent sorting. Dr. Mallampalli uses gene transfer approaches to express new CCT mutant enzymes in alveolar epithelia that are resistant to proteolysis and phosphorylation events thereby restoring surfactant PC to high levels in alveolar injury.



Recent Publications: