|O2-sensing: Hypoxic pulmonary vasoconstriction (HPV) matches perfusion to ventilation. We study the “Redox Theory” of HPV. The identity and function of a mitochondrial O2-sensor in smooth muscle cell and its effects on ion channels and rho kinase is assessed.
|Pulmonary arterial hypertension (PAH): PAH is an obliterative pulmonary vasculopathy resulting in death from right ventricular (RV) failure. The cancer-like proliferation/apoptosis imbalance in the vasculature and RV is studied, focusing on: 1) HIF-1a and pyruvate dehydrogenase kinase (PDK) activation 2) epigenetic silencing of SOD2 3) disordered mitochondrial fusion and fission 4) RV microvascular rarefaction and cancer-like metabolism.|
|Metabolism, fusion and fission in cancer: The lab investigates mitochondrial and metabolic therapies for cancer, including the role of DRP-1-mediated fission and mitofusin-2-mediated fusion.|
|Ductus arteriosus (DA): O2-induced constriction of human DA results from PO2-dependent inhibition of O2-sensitive, Kv channels in myocytes. The role of mitochondrial fission in redox-based O2-sensing and implications for DA constriction/closure are studied.|