Loveth Asiabaka

My thesis focuses on investigating the mechanism by which Mixed Lineage Kinase 3 (MLK3) opposes pathological cardiac hypertrophy through inhibition of the transcription factor; Nuclear Factor of Activated T Cells (NFAT) in the cardiac myocyte. NFAT was identified to promote pathological cardiac hypertrophy through downstream MLK3 regulation. More recently, the Mitogen Activated Protein (MAP) Kinase; JNK (Jun N-terminals Kinase) was found to phosphorylate NFAT through downstream mechanism. Thus, preventing NFAT from translocating into the nucleus where it initiates pathological cardiac hypertrophy.  We also know that MLK3 promotes JNK activation, which is implicated in heart failure and that MLK3 increases NFAT activity and MLK3 kinase inhibition worsens left ventricular function. Therefore, the goal of my research would be to first test the hypothesis whether administration of a MLK3 inhibitor (URMC-099) can also increase NFAT activation before proceeding to other investigations.