The role of megalin in AKI, and the transition to CKD
This VA supported research examines the role of megalin in AKI, and the transition to CKD. AKI is a major contributor to morbidity, mortality and higher cost of care. Early on, Dr. Hamad’s lab found that stanniocalcin-1 (a mitochondrial intracrine) overexpression in mice confers resistance to ischemic AKI. Later, Dr. Hamad’s lab found that megalin shuttles hormones (stanniocalcin-1, angiotensin-II and TGF-β) from the cell-surface to the mitochondria and mapped the internalization pathway. Importantly, deletion of megalin specifically in tubular epithelial cells in mice aggravates AKI and accelerates the progression to CKD. Dr. Hamad’s lab is currently examining pathways of injury that are triggered by deletion of megalin.
Pathways of injury and potential therapeutic targets
Mesoamerican nephropathy is a form of CKD prevalent in agricultural communities in Central America and many other agricultural communities worldwide (India, Sri Lanka, Thailand, Egypt, Argentina, etc.). It affects predominantly young male subjects. This advanced research project is based on observations linking CKD in migrant workers (surveyed in a Houston safety net hospital) with past exposure to agrochemicals and heavy metals. In a mouse model for the disease (repeated injections of the herbicide paraquat), Dr. Hamad’s lab identified pathways of injury and potential therapeutic targets. Future research will focus on those targets.
