The laboratory of Prof. Keiji Kuba investigates the molecular pathogenesis and pathology of cardiovascular diseases, by focusing on RNA metabolism and peptide signaling. Our overall mission is “To identify novel genes, pathways, and mechanisms critical in contributing to pathogenesis and advancements of cardiovascular diseases.” Current research interests in the Kuba lab include the regulation of mRNA decay/deadenylation, mRNA transcription/decay coupling, vasoactive peptide signaling, and energy metabolism in cardiovascular systems.

We elucidated several new mechanisms for pathogenesis of cardiovascular diseases. We had identified angiotensin converting enzyme 2 (ACE2), as an in vivo SARS-coronavirus receptor and demonstrated that ACE2 plays a crucial role in SARS pathogenesis (Nature 2005, Nat Med. 2005). We elucidated Apelin, a new peptide hormone as well as a substrate for ACE2 is a crucial regulator of heart contractility (Circ Res 2007) and recently demonstrated that Apelin – ACE2 – Angiotensin 1-7 axis is essential compensatory pathway in failing hearts (JCI 2013). In lipid library screening and metabolome analysis, we discovered Protectin D1, a lipid mediator, as a novel regulator of influenza virus RNA export, which suppresses influenza virus replication (Cell 2013). In genome-wide in vivo RNAi fly library screening (collaboration with IMBA), we identified CCR4-NOT complex, especially CNOT3 subunit, as a novel regulator of heart functions (Cell 2010). CCR4-NOT was originally isolated as a global transcription regulator from yeast mutants, and it has recently been shown as a crucial deadenylase for mRNA poly-A tail shortening. Currently, we hypothesize that CCR4-NOT complex is a global regulator of gene expression linking metabolism of mRNA and epigenetic gene regulation.