The ASPIRE Path in Molecular Medicine

I wanted to be in a research field that has implications in human health and diseases and having done my master’s in microbiology and PhD in Biochemistry, I found the perfect opportunity at the VUMC. Being apart of Dr. Vanacore’s research group and the Nephrology department has given me insight on how protein biochemistry can be used to study kidney fibrosis and design strategies that will shed light into themolecular aspects that feeds into the progression of the disease. These insights will then further help in identifying possible ways that will reduce/prevent fibrosis by designing drugs that target these molecularmechanisms and help slow the disease progression.The overarching goal of my projects is to characterize the role of lysyl oxidase like 2 (LOXL2) in the development, pathogenesis and progression of chronic kidney disease. LOXL2 is an amine oxidase enzyme which belongs to the family of lysyl oxidases. These enzymes are known to oxidize peptidyl lysines in collagen and elastin in the extracellular matrix (ECM). This oxidation leads to the formation of side chain aldehyde which can react with other neighboring oxidized lysines or with native unmodified lysine to form inter and intrachain crosslinkages. These crosslinks provide structural stability to the ECM and play an important role in biological homeostasis. However, increased LOXL2-mediated crosslinking has been shown to contribute to tissue fibrosis, including chronic kidney disease.