Andy Cuzco, FCLC 2024

MAJOR: Natural Science

BIO: Andy is a senior in the Honors Program at Fordham College at Lincoln Center, majoring in the Natural Sciences. This past summer, he conducted research at the Salk Institute in San Diego, where he used fluorescence microscopy to study the role of the INF2 protein in Charcot Marie Tooth disease. After graduation, he plans to attend medical school and eventually become a physician-scientist. In his free time, he enjoys soccer, photography, and weightlifting.

PROJECT TITLE: Disruptions to INF2-mediated actin polymerization and their impact on lysosomal function

MENTOR: Jason Morris, Department of Natural Science

ABSTRACT: Lysosomes are membrane bound organelles responsible for the breakdown and digestion of external and internal biological macromolecules. When lysosomal function is impaired, defective proteins and organelles aggregate and disrupt healthy cell functions. Impaired lysosomal mediated autophagy is a common histological hallmark of many neurodegenerative diseases, including a group of neurological disorders known collectively as Charcot Marie Tooth (CMT) disease. Recently, an ER localized formin, INF2-CAAX has emerged as a candidate for a CMT-associated protein that affects organelle mobility in diseased cells. More specifically, mutant INF2 has been shown to decrease mobility of lysosomes. Interestingly, decreasing INF2 activity also affects lysosome morphology and mobility. INF2 knock-out results in reduced lysosomal mobility and lysosomal enlargement in U2OS cells. In both cases, it's unclear whether lysosomal function is affected as well. Therefore, we were interested in how increases and decreases in INF2 activity affect lysosomal function. In this study, we look at lysosomal mass and acidity in INF2 knockout and wildtype U2OS cells as a readout of lysosomal function. We also look at the same measures in patient derived fibroblasts. We demonstrate that lysosomal mass in both KOs and CMT patient derived fibroblasts (CMTs) is decreased. We also show a decrease in lysosomal acidity in both KOs and in CMTs.