The department’s basic pulmonary research primarily focuses on understanding the cellular and molecular basis of lung disease in adulthood that has its origins in the fetus and newborns using preclinical models of acute and chronic lung diseases, as well as clinical samples.
Dr. J. Usha Raj’s research interests are in the area of Developmental Pulmonary Vascular Biology and Pulmonary Hypertension. Her lab is studying the normal physiological mechanisms that control the pulmonary circulation in the fetus and newborn. She is also studying the mechanisms of Pulmonary Hypertension both in the developing and adult lung. Her laboratory is currently involved in the followings areas of investigation:
- Mechanisms by which cGMP-dependent protein kinase activity undergoes post-translational modification in hypoxia and becomes inactive, in a reversible manner, using fetal and newborn lamb models.
- Investigating the role of the miRNA cluster 17~92 in the pathogenesis of pulmonary hypertension in the adults using genetic models and human tissues.
- The study of epigenetic phenomenon induced by perinatal hypoxia that predispose to the development of pulmonary hypertension in adult life using a mouse model.
All her studies are related to the biology of the smooth muscle cell in the pulmonary vasculature, particularly the factors that regulate vasomotor tone as well as cell proliferation and phenotype maintenance.
Dr. Reddy’s research focuses on Host-Defense Response during Acute Lung Injury and Repair, especially the role of redox imbalance in the dysregulated inflammatory response and abnormal resolution of lung inflammation and injury in neonates and adults. His laboratory found that disruption of the crucial oxidative stress modifier, the Nrf2 transcription factor, impairs the resolution of hyperoxic lung injury, leading to defective tissue repair and persistent inflammation as well as promoting susceptibility to bacterial infection. He also studies the functions of AP-1 (c-Jun and Fra-1) signaling in resolving lung inflammation and injury, and in modulating emphysema and cancer. His ongoing research focus on:
- Mechanisms of regulation and functions of both inflammatory and lung cell type specific Nrf2-mediated redox signaling during lung injury and repair and infection using conditional knockout mouse models and primary cultures.
- Understanding the interplay between Nrf2 and Fra-1/AP-1 transcription factor in the modulation of abnormal vascular and epithelial repair after tissue injury using genetic and knockdown approaches in vivo and in vitro.
- Studying the regulation and functions of Jun/Fra-1 signaling in cigarette smoke-induced emphysema and lung cancer.
All his studies are to explore whether targeting of Nrf2 and AP-1 signaling pharmacologically will provide a promising approach to intervene and improve the outcomes of acute lung injury and lung pathogenesis in neonates and adults and using preclinical models and clinical samples ex-vivo.
Dr. Zhou is studying the roles of hypoxia signaling in the lung diseases. His lab is studying the molecular mechanisms controlling the behavior of interstitial lung fibroblasts and pulmonary artery smooth muscle cells and their implication in the pathogenesis of pulmonary fibrosis and pulmonary hypertension. His lab is actively pursuing the following area of research:
- The role of the von Hippel Lindau (VHL) protein in pulmonary fibrosis. VHL is a component of E3 ligase, which regulates HIF signaling, a key element in cellular adaptation to hypoxia. His laboratory found that expression of VHL is elevated in fibrotic tissues and loss of VHL prevents fibroblast proliferation and development of fibrosis in an experimental mouse model. His laboratory is particularly interested in how VHL regulates cell matrix proteins in a HIF independent pathway to regulate lung fibroblast proliferation, migration and differentiation.
- Functions of Adenosine Monophosphate Protein Kinase (AMPK) in pulmonary artery smooth muscle cell survival and proliferation during the development of pulmonary hypertension. Dr. Zhou’s laboratory has shown that AMPK is activated in pulmonary artery smooth muscle cells of patients with pulmonary hypertension and experimental hypertensive mice. They also found that inhibition of AMPK causes the death of pulmonary artery smooth muscle cells when exposed to hypoxia. His research is focusing on elucidating the molecular mechanisms underlying AMPK-mediated cell survival.
He is also exploring to target these two proteins to develop novel approaches for the treatment of patients with pulmonary fibrosis and pulmonary hypertension.
Dr. Harijith’s research interests are in the area of Acute Lung Injury (ALI) and Bronchopulmonary Dysplasia (BPD). He is studying the role of Sphingolipid signaling in hyperoxia-induced disruption of lung development, under the mentorship by Dr. Viswanathan Natarajan. He is currently involved in the followings areas of investigation using cell systems and genetic models:
- Mechanisms by which Sphingosine Kinase signaling affects generation of Reactive Oxygen Species (ROS).
- Mechanisms by which ROS could affect formation of alveoli in BPD.
- The study of NADPH oxidases functions and their relationship with Sphingolipid signaling pathways in mediating ROS-induced lung injury and BPD.
His goal is to understand the pathogenic mechanisms of BPD and to develop novel approaches to mitigate the chronic lung disease.